Trial Outcomes & Findings for Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer (NCT NCT02744092)

Last Updated: 2023-10-03

Results Overview

To compare the effectiveness of anticoagulation with a DOAC (intervention) with LMWH/warfarin (comparator) for preventing VTE recurrence in patients with cancer based on cumulative VTE recurrence reported by patients or clinicians at 6 months. Only VTEs that were nonfatal were considered because of the challenges of attributing cause of death in cancer patients to tumor progression vs. VTE.

Recruitment status

COMPLETED

Study phase

Target enrollment

811 participants

Primary outcome timeframe

6 months

Results posted on

2023-10-03

Participant Flow

Patients were recruited from 67 US-based healthcare institutions between December 2016 and April 2020.

Participant milestones

Participant milestones
Measure	Randomized Arm 1 (DOACs) Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Enrolled & Received Selected Treatment STARTED	335	336	108	32
Enrolled & Received Selected Treatment Received Assigned Treatment (Apixaban)	193	0	57	0
Enrolled & Received Selected Treatment Received Assigned Treatment (Rivaroxaban)	122	0	48	0
Enrolled & Received Selected Treatment Received Assigned Treatment (Dabigatran)	9	0	2	0
Enrolled & Received Selected Treatment Received Assigned Treatment (Edoxaban)	6	0	0	0
Enrolled & Received Selected Treatment Received Assigned Treatment (Enoxaparin)	0	277	0	24
Enrolled & Received Selected Treatment Received Assigned Treatment (Fondaparinux)	0	23	0	6
Enrolled & Received Selected Treatment Received Assigned Treatment (Dalteparin)	0	8	0	0
Enrolled & Received Selected Treatment Did Not Receive Assigned/Selected Treatment	5	28	1	2
Enrolled & Received Selected Treatment COMPLETED	330	308	107	30
Enrolled & Received Selected Treatment NOT COMPLETED	5	28	1	2
6-Month Clinical Outcomes(Chart Review) STARTED	330	308	107	30
6-Month Clinical Outcomes(Chart Review) COMPLETED	330	308	107	30
6-Month Clinical Outcomes(Chart Review) NOT COMPLETED	0	0	0	0
3-Month Patient-Reported Outcomes Survey STARTED	330	308	107	30
3-Month Patient-Reported Outcomes Survey Approached for 3-month Survey	295	280	99	26
3-Month Patient-Reported Outcomes Survey COMPLETED	212	197	77	16
3-Month Patient-Reported Outcomes Survey NOT COMPLETED	118	111	30	14
6-Month Patient-Reported Outcomes Survey STARTED	330	308	107	30
6-Month Patient-Reported Outcomes Survey Approached for 6-month Survey	262	253	89	21
6-Month Patient-Reported Outcomes Survey COMPLETED	191	177	75	12
6-Month Patient-Reported Outcomes Survey NOT COMPLETED	139	131	32	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Randomized Arm 2 (LMWH) n=308 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Randomized Arm 1 (DOACs) n=330 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=107 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=30 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Total n=775 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	197 Participants n=7 Participants	175 Participants n=5 Participants	45 Participants n=5 Participants	11 Participants n=4 Participants	428 Participants n=21 Participants
Age, Categorical >=65 years	111 Participants n=7 Participants	155 Participants n=5 Participants	62 Participants n=5 Participants	19 Participants n=4 Participants	347 Participants n=21 Participants
Age, Customized Age, median (q1, q3)	62 years n=7 Participants	64 years n=5 Participants	66 years n=5 Participants	67 years n=4 Participants	64 years n=21 Participants
Sex/Gender, Customized Female	172 Participants n=7 Participants	181 Participants n=5 Participants	51 Participants n=5 Participants	18 Participants n=4 Participants	422 Participants n=21 Participants
Sex/Gender, Customized Male	136 Participants n=7 Participants	149 Participants n=5 Participants	56 Participants n=5 Participants	12 Participants n=4 Participants	353 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=7 Participants	15 Participants n=5 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	33 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	287 Participants n=7 Participants	306 Participants n=5 Participants	101 Participants n=5 Participants	28 Participants n=4 Participants	722 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=7 Participants	9 Participants n=5 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	20 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race (NIH/OMB) Asian	6 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	14 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	38 Participants n=7 Participants	39 Participants n=5 Participants	12 Participants n=5 Participants	3 Participants n=4 Participants	92 Participants n=21 Participants
Race (NIH/OMB) White	255 Participants n=7 Participants	277 Participants n=5 Participants	90 Participants n=5 Participants	23 Participants n=4 Participants	645 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=7 Participants	7 Participants n=5 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	17 Participants n=21 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Primary analyses were performed on the participants who began protocol-directed therapy, the "as treated" population.

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=330 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=308 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=107 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=30 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Cumulative Non-Fatal VTE Recurrence at 6 Months (%)	6.1 percentage of patients	8.8 percentage of patients	7.5 percentage of patients	4.1 percentage of patients

SECONDARY outcome

Timeframe: 6 months

Population: Primary analyses were performed on the participants who began protocol-directed therapy, the "as treated" population.

To compare the harms of DOAC vs. LMWH/warfarin therapy for cancer patients with VTE based on the cumulative rate of major bleeding at 6 months. d. Major bleeding was defined as Grade \>=3 on the Common Terminology Criteria for Adverse Events from the National Cancer Institute (NCI CTCAE) criteria version 5.0 (i.e., severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living).

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=330 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=308 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=107 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=30 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Cumulative Rates of Major Bleeding	5.2 percentage of patients	5.6 percentage of patients	11.5 percentage of patients	7.6 percentage of patients

SECONDARY outcome

Timeframe: 3 months

Population: Participants completing the 3-month survey assessment

Change in physical health at 3 months. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The presented scores in this results section indicate the change (difference) in mean scores between the baseline and 3-month follow-up assessment.

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=212 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=197 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=77 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=16 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire	1.8 units on a scale Interval 0.6 to 3.0	0.7 units on a scale Interval -0.5 to 2.0	3.4 units on a scale Interval 0.4 to 6.3	-0.3 units on a scale Interval -8.7 to 8.1

SECONDARY outcome

Timeframe: 3 months

Population: Participants completing the 3-month survey assessment

To compare the burden of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 3 months. The burden scale has12 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS burden tool is then scored using the totals from each question with a total score from 12 to 60 possible. Higher scores signify greater satisfaction (lower burden).

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=212 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=197 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=77 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=16 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Burden of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire	56.7 score on a scale Interval 56.1 to 57.3	53.3 score on a scale Interval 52.5 to 54.2	55.8 score on a scale Interval 54.8 to 56.9	54.9 score on a scale Interval 52.4 to 57.4

SECONDARY outcome

Timeframe: 6 months

Population: Primary analyses were performed on the participants who began protocol-directed therapy, the "as treated" population.

To compare the impact of DOAC vs. LMWH/warfarin therapy on mortality in cancer patients with VTE based on survival at 6 months. Mortality was reported by participants' surrogates (via study-specific questionnaire) or clinicians (via study-specific case report form)

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=330 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=308 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=107 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=30 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Mortality Reported by Participants' Surrogates (Via Study-specific Questionnaire) or Clinicians (Via Study-specific Case Report Form)	21.5 percentage of patients	18.4 percentage of patients	16.3 percentage of patients	23.8 percentage of patients

SECONDARY outcome

Timeframe: 6 months

Population: Participants completing the 6-month survey assessment

Change in physical health at 6 months. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The presented scores in this results section indicate the change (difference) in mean scores between the baseline and 6-month follow-up assessment.

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=191 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=177 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=75 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=12 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire	2.4 units on a scale Interval 0.9 to 3.8	0.7 units on a scale Interval -0.8 to 2.2	2.1 units on a scale Interval -0.3 to 4.5	-2.8 units on a scale Interval -10.4 to 4.9

SECONDARY outcome

Timeframe: 6 months

Population: Participants completing the 6-month survey assessment

To compare the burden of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 6 months. The burden scale has12 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS burden tool is then scored using the totals from each question with a total score from 12 to 60 possible. Higher scores signify greater satisfaction (lower burden).

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=191 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=177 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=75 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=12 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Burden of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire	56.5 score on a scale Interval 55.8 to 57.1	54.1 score on a scale Interval 53.2 to 55.1	54.9 score on a scale Interval 53.4 to 56.4	53.1 score on a scale Interval 49.8 to 56.3

SECONDARY outcome

Timeframe: 3-months

Population: Participants completing the 3-month survey assessment

To compare the benefit of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 3 months. The benefits scale has 3 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS benefits tool is then scored using the totals from each question with a total score from 3 to 15 possible. Higher scores signify greater satisfaction (greater benefits).

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=212 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=197 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=77 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=16 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Benefit of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire	11.2 score on a scale Interval 10.7 to 11.6	10.7 score on a scale Interval 10.3 to 11.2	10.3 score on a scale Interval 9.6 to 11.0	10.5 score on a scale Interval 8.9 to 12.1

SECONDARY outcome

Timeframe: 6-months

Population: Participants completing the 6-moth survey assessment

To compare the benefit of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 6 months. The benefits scale has 3 items and patients are asked to rate their experiences on a 5-point scale of intensity (1=not at all, 2=a little, 3=moderately, 4=quite a bit, 5=extremely). The ACTS benefits tool is then scored using the totals from each question with a total score from 3 to 15 possible. Higher scores signify greater satisfaction (greater benefits).

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=191 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=177 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=75 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=12 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Benefit of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire	11.6 score on a scale Interval 11.1 to 12.1	11.3 score on a scale Interval 10.8 to 11.8	11.5 score on a scale Interval 10.8 to 12.1	10.1 score on a scale Interval 8.6 to 11.6

SECONDARY outcome

Timeframe: 3-months

Population: Participants completing the 3-month survey assessment

Change in mental health at 3 months from baseline. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The scores indicate change in score from baseline.

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=212 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=197 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=77 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=16 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Health Related Quality of Life (Mental Health) Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire at 3-months	-0.3 units on a scale Interval -1.8 to 1.1	0.7 units on a scale Interval -0.6 to 2.1	0.3 units on a scale Interval -2.1 to 2.6	0.4 units on a scale Interval -4.5 to 5.3

SECONDARY outcome

Timeframe: 6-months

Population: Participants completing the 6-month survey assessment

Change in mental health at 6 months from baseline. Health-related quality of life was measured using the 12-Item Short Form Health Survey (SF-12) sub-scales for physical and mental health (score range, 0-100; higher scores indicate better physical and mental health functioning). Survey content included minor verbiage changes for clarity. The scores indicate change in score from baseline.

Outcome measures

Outcome measures
Measure	Randomized Arm 1 (DOACs) n=191 Participants Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=177 Participants Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=75 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=12 Participants If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Health Related Quality of Life (Mental Health) Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire at 6-months	0.3 units on a scale Interval -1.1 to 1.7	0.9 units on a scale Interval -0.5 to 2.3	1.1 units on a scale Interval -1.1 to 3.3	-1.9 units on a scale Interval -7.0 to 3.3

Adverse Events

Randomized Arm 1 (DOACs)

Serious events: 123 serious events

Other events: 6 other events

Deaths: 70 deaths

Randomized Arm 2 (LMWH)

Serious events: 114 serious events

Other events: 11 other events

Deaths: 56 deaths

Preference Cohort 1 (DOACs)

Serious events: 51 serious events

Other events: 3 other events

Deaths: 18 deaths

Preference Cohort 2 (LMWH)

Serious events: 16 serious events

Other events: 2 other events

Deaths: 9 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Jean Connors

Dana-Farber Cancer Institute

Phone: (617) 632-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Complete study results are available in JAMA.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	Randomized Arm 1 (DOACs) n=330 participants at risk Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=308 participants at risk Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=107 participants at risk If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=30 participants at risk If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Blood and lymphatic system disorders Anemia	4.5% 15/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.2% 10/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	6.5% 7/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	10.0% 3/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Blood and lymphatic system disorders Leukocytosis	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Atrial fibrillation	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.9% 2/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Atrial flutter	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Cardiac arrest	0.91% 3/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Chest pain - cardiac	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Heart failure	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Pericardial effusion	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Pericardial tamponade	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Sinus tachycardia	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Cardiac disorders Cardiac disorders - Other, specify	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Endocrine disorders Hypothyroidism	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Eye disorders Eye disorders - Other, specify	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Ascites	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Colitis	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.9% 2/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Colonic obstruction	0.91% 3/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Colonic	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Diarrhea	0.91% 3/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Dysphagia	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Esophagitis	0.61% 2/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Gastric hemorrhage	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Gastric ulcer	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Lower GI hemorrhage	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Mucositis oral	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Nausea	0.91% 3/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.3% 4/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Obstruction gastric	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Pancreatitis	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Rectal hemorrhage	1.2% 4/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.97% 3/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.9% 2/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Rectal pain	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Small intestinal obstruction	0.91% 3/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Upper gastrointestinal hemorrhage	0.61% 2/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Vomiting	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.3% 4/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Abdominal pain	2.4% 8/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.97% 3/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	2.8% 3/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	10.0% 3/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Death NOS	10.3% 34/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	10.7% 33/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	4.7% 5/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Edema limbs	0.61% 2/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Fatigue	1.2% 4/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	2.8% 3/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Fever	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Multi-organ failure	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Non-cardiac chest pain	0.61% 2/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.

Other adverse events
Measure	Randomized Arm 1 (DOACs) n=330 participants at risk Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Randomized Arm 2 (LMWH) n=308 participants at risk Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.	Preference Cohort 1 (DOACs) n=107 participants at risk If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). Rivaroxaban: Anticoagulation therapy. Apixaban: Anticoagulation therapy. Edoxaban: Anticoagulation therapy. Dabigatran: Anticoagulation therapy.	Preference Cohort 2 (LMWH) n=30 participants at risk If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized). Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with Low Molecular Weight Heparin (LMWH) with or without a transition to warfarin. Warfarin: Anticoagulation therapy. Dalteparin: Anticoagulation therapy. Enoxaparin: Anticoagulation therapy. Fondaparinux: Anticoagulation therapy.
Vascular disorders Hematoma	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	6.7% 2/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Diarrhea	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	6.7% 2/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Blood and lymphatic system disorders Anemia	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.6% 5/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Eye disorders Blurred vision	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Constipation	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Dyspepsia	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Nausea	0.91% 3/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.9% 2/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Vomiting	0.61% 2/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Gastrointestinal disorders Abdominal Pain	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.3% 4/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
General disorders Fever	1.5% 5/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.65% 2/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	2.8% 3/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Injury, poisoning and procedural complications Fracture	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Metabolism and nutrition disorders Hyperkalemia	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Nervous system disorders Dizziness	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Nervous system disorders Seizure	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Nervous system disorders Stroke	0.00% 0/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.93% 1/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Psychiatric disorders Confusion	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Renal and urinary disorders Acute kidney injury	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.32% 1/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Respiratory, thoracic and mediastinal disorders Laryngeal hemorrhage	0.30% 1/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	0.00% 0/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.
Vascular disorders Thromboembolic event	1.5% 5/330 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.6% 11/308 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	1.9% 2/107 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.	3.3% 1/30 • Adverse event (AE) data was collected for 6-months. AEs were reported by physicians. Grade 3+ AEs were severe. Other AEs are grade 1 or 2 . Other AE section reports on events that were experienced in \>1% of patients, so total # of patients may not match the # of patients experiencing events. We did not report AEs by individual drug arm because we did not randomize drugs; comparisons amongst drugs will be subject to selection bias. Also, the protocol allowed patients to switch drugs, so it would be unclear which AE is affiliated with which drug.