Trial Outcomes & Findings for Extended Steroid in Use in Community Acquired Pneumonia (CAP)(e) (NCT NCT01283009)

Last Updated: 2020-10-08

Results Overview

The primary outcome is all-cause mortality at 60 days, defined by whether the patient has died by the end of study day 60.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

584 participants

Primary outcome timeframe

60-day

Results posted on

2020-10-08

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: Inactive Substance Inactive substance Inactive Substance: Inactive Substance will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).	Arm 2: Methylprednisolone Methylprednisolone Methylprednisolone: Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).
Overall Study STARTED	287	297
Overall Study COMPLETED	169	180
Overall Study NOT COMPLETED	118	117

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: Inactive Substance Inactive substance Inactive Substance: Inactive Substance will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).	Arm 2: Methylprednisolone Methylprednisolone Methylprednisolone: Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).
Overall Study Death	83	78
Overall Study Study ended early	23	26
Overall Study Withdrawal by Subject	10	8
Overall Study Physician Decision	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Patient Withdrawn by LAR/DPOA	0	4

Baseline Characteristics

One participant in Arm 1 was missing the demographic information form.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 60-day

Population: Numbers provided are overall and by stratum.

The primary outcome is all-cause mortality at 60 days, defined by whether the patient has died by the end of study day 60.

Outcome measures

Outcome measures
Measure	Arm 1: Inactive Substance n=287 Participants Inactive substance Inactive substance will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).	Arm 2: Methylprednisolone n=297 Participants Methylprednisolone Methylprednisolone: Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).
60-day Mortality Died on or prior to study day 60 · Yes	50 Participants	47 Participants
60-day Mortality Died on or prior to study day 60 · No	227 Participants	239 Participants
60-day Mortality Died on or prior to study day 60 · Unknown	10 Participants	11 Participants
60-day Mortality On Mechanical Ventilation at Study Entry · Yes	24 Participants	22 Participants
60-day Mortality On Mechanical Ventilation at Study Entry · No	70 Participants	72 Participants
60-day Mortality On Mechanical Ventilation at Study Entry · Unknown	2 Participants	3 Participants
60-day Mortality Not on Mechanical Ventilation · Yes	26 Participants	25 Participants
60-day Mortality Not on Mechanical Ventilation · No	157 Participants	167 Participants
60-day Mortality Not on Mechanical Ventilation · Unknown	8 Participants	8 Participants

Adverse Events

Arm 1: Inactive Substance

Serious events: 162 serious events

Other events: 0 other events

Deaths: 84 deaths

Arm 2: Methylprednisolone

Serious events: 167 serious events

Other events: 0 other events

Deaths: 79 deaths

Serious adverse events

Other adverse events

Adverse event data not reported

Additional Information

Dr. Gianfranco U. Meduri

Memphis VA Medical Center

Phone: (901) 577-7520

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Baseline characteristics by cohort
Measure	Arm 1: Inactive Substance n=287 Participants Inactive substance Inactive substance will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).	Arm 2: Methylprednisolone n=297 Participants Methylprednisolone Methylprednisolone: Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).	Total n=584 Participants Total of all reporting groups
Age, Continuous	68.6 years STANDARD_DEVIATION 11.1 • n=286 Participants • One participant in Arm 1 was missing the demographic information form.	69.0 years STANDARD_DEVIATION 10.8 • n=297 Participants • One participant in Arm 1 was missing the demographic information form.	68.8 years STANDARD_DEVIATION 11.0 • n=583 Participants • One participant in Arm 1 was missing the demographic information form.
Sex: Female, Male Female	13 Participants n=286 Participants • One participant in Arm 1 was missing the demographic information form.	8 Participants n=297 Participants • One participant in Arm 1 was missing the demographic information form.	21 Participants n=583 Participants • One participant in Arm 1 was missing the demographic information form.
Sex: Female, Male Male	273 Participants n=286 Participants • One participant in Arm 1 was missing the demographic information form.	289 Participants n=297 Participants • One participant in Arm 1 was missing the demographic information form.	562 Participants n=583 Participants • One participant in Arm 1 was missing the demographic information form.
Race/Ethnicity, Customized Ethnicity · Not Spanish, Hispanic or Latino	251 Participants n=280 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	255 Participants n=286 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	506 Participants n=566 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.
Race/Ethnicity, Customized Ethnicity · Mexican, Mexican American, or Chicano	12 Participants n=280 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	16 Participants n=286 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	28 Participants n=566 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.
Race/Ethnicity, Customized Ethnicity · Puerto Rican	8 Participants n=280 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	5 Participants n=286 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	13 Participants n=566 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.
Race/Ethnicity, Customized Ethnicity · Cuban	1 Participants n=280 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	0 Participants n=286 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	1 Participants n=566 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.
Race/Ethnicity, Customized Ethnicity · Other Spanish, Hispanic, or Latino	8 Participants n=280 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	10 Participants n=286 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.	18 Participants n=566 Participants • Eleven participants in Arm 1, and six participants in Arm 2 were missing information on ethnicity.
Race/Ethnicity, Customized White	227 Participants n=281 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.	245 Participants n=287 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.	472 Participants n=568 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.
Race/Ethnicity, Customized Black/African American	48 Participants n=281 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.	36 Participants n=287 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.	84 Participants n=568 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.
Race/Ethnicity, Customized Other	10 Participants n=281 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.	15 Participants n=287 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.	25 Participants n=568 Participants • Race is check all that apply. Therefore, the numbers for individual categories do not add up to the number of patient randomized.
BMI >=30 Yes	70 Participants n=285 Participants • Two participants in Arm 1 are missing this value.	62 Participants n=297 Participants • Two participants in Arm 1 are missing this value.	132 Participants n=582 Participants • Two participants in Arm 1 are missing this value.
BMI >=30 No	215 Participants n=285 Participants • Two participants in Arm 1 are missing this value.	235 Participants n=297 Participants • Two participants in Arm 1 are missing this value.	450 Participants n=582 Participants • Two participants in Arm 1 are missing this value.
Mechanical Ventilation at Study Entry Yes	96 Participants n=287 Participants	97 Participants n=297 Participants	193 Participants n=584 Participants
Mechanical Ventilation at Study Entry No	191 Participants n=287 Participants	200 Participants n=297 Participants	391 Participants n=584 Participants
SOFA Score	6.29 units on a scale STANDARD_DEVIATION 2.85 • n=285 Participants • The number analyzed in Arm 1 is different from the overall due to missing values.	6.68 units on a scale STANDARD_DEVIATION 3.0 • n=297 Participants • The number analyzed in Arm 1 is different from the overall due to missing values.	6.49 units on a scale STANDARD_DEVIATION 2.93 • n=582 Participants • The number analyzed in Arm 1 is different from the overall due to missing values.
Vasopressor Dependent Shock at or Prior to Study Entry Yes	32 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	44 Participants n=296 Participants • The number analyzed is different from the overall due to missing values.	76 Participants n=581 Participants • The number analyzed is different from the overall due to missing values.
Vasopressor Dependent Shock at or Prior to Study Entry No	253 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	252 Participants n=296 Participants • The number analyzed is different from the overall due to missing values.	505 Participants n=581 Participants • The number analyzed is different from the overall due to missing values.
Any Major Co-Morbidities Yes	275 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	290 Participants n=297 Participants • The number analyzed is different from the overall due to missing values.	565 Participants n=582 Participants • The number analyzed is different from the overall due to missing values.
Any Major Co-Morbidities No	10 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	7 Participants n=297 Participants • The number analyzed is different from the overall due to missing values.	17 Participants n=582 Participants • The number analyzed is different from the overall due to missing values.
Number of Major Co-Morbidities	3.9 Comorbidities STANDARD_DEVIATION 1.9 • n=285 Participants • The number analyzed is different from the overall due to missing values.	4.0 Comorbidities STANDARD_DEVIATION 1.8 • n=297 Participants • The number analyzed is different from the overall due to missing values.	4.0 Comorbidities STANDARD_DEVIATION 1.8 • n=582 Participants • The number analyzed is different from the overall due to missing values.
Charlson Comorbidity Index	5.65 comorbidity score STANDARD_DEVIATION 2.24 • n=285 Participants • The number analyzed is different from the overall due to missing values.	5.77 comorbidity score STANDARD_DEVIATION 2.39 • n=297 Participants • The number analyzed is different from the overall due to missing values.	5.71 comorbidity score STANDARD_DEVIATION 2.32 • n=582 Participants • The number analyzed is different from the overall due to missing values.
ACE 27 Overall Comorbidity Score 0 (None)	8 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	6 Participants n=297 Participants • The number analyzed is different from the overall due to missing values.	14 Participants n=582 Participants • The number analyzed is different from the overall due to missing values.
ACE 27 Overall Comorbidity Score 1 (Mild)	33 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	38 Participants n=297 Participants • The number analyzed is different from the overall due to missing values.	71 Participants n=582 Participants • The number analyzed is different from the overall due to missing values.
ACE 27 Overall Comorbidity Score 2 (Moderate)	59 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	51 Participants n=297 Participants • The number analyzed is different from the overall due to missing values.	110 Participants n=582 Participants • The number analyzed is different from the overall due to missing values.
ACE 27 Overall Comorbidity Score 3 (Severe)	185 Participants n=285 Participants • The number analyzed is different from the overall due to missing values.	202 Participants n=297 Participants • The number analyzed is different from the overall due to missing values.	387 Participants n=582 Participants • The number analyzed is different from the overall due to missing values.
ACE 27 total score	2.48 units on a scale n=285 Participants • The number analyzed is different from the overall due to missing values.	2.51 units on a scale n=297 Participants • The number analyzed is different from the overall due to missing values.	2.50 units on a scale n=582 Participants • The number analyzed is different from the overall due to missing values.
Karnofsky Performance Score	72.9 units on a scale n=280 Participants • The number analyzed is different from the overall due to missing values.	72.4 units on a scale n=291 Participants • The number analyzed is different from the overall due to missing values.	72.6 units on a scale n=571 Participants • The number analyzed is different from the overall due to missing values.
Health Care Associated Pneumonia Pts. w/No HCAP (%)	198 Participants n=287 Participants	185 Participants n=297 Participants	383 Participants n=584 Participants
Health Care Associated Pneumonia Pts. with HCAP (%)	89 Participants n=287 Participants	112 Participants n=297 Participants	201 Participants n=584 Participants
Admission from the Ward Pts. Admitted from Ward (%)	57 Participants n=287 Participants	66 Participants n=297 Participants	123 Participants n=584 Participants
Admission from the Ward Pts. not Admitted from Ward (%)	230 Participants n=287 Participants	231 Participants n=297 Participants	461 Participants n=584 Participants
Pneumonia Severity Index (PSI) Score	122.3 Severity Score STANDARD_DEVIATION 34.4 • n=286 Participants • The number analyzed is different from the overall due to missing values.	125.6 Severity Score STANDARD_DEVIATION 37.2 • n=297 Participants • The number analyzed is different from the overall due to missing values.	124.0 Severity Score STANDARD_DEVIATION 35.8 • n=583 Participants • The number analyzed is different from the overall due to missing values.
Pneumonia Severity Index (PSI) Class I	4 Participants n=285 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	3 Participants n=297 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	7 Participants n=582 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.
Pneumonia Severity Index (PSI) Class II	13 Participants n=285 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	13 Participants n=297 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	26 Participants n=582 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.
Pneumonia Severity Index (PSI) Class III	29 Participants n=285 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	41 Participants n=297 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	70 Participants n=582 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.
Pneumonia Severity Index (PSI) Class IV	126 Participants n=285 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	121 Participants n=297 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	247 Participants n=582 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.
Pneumonia Severity Index (PSI) Class V	113 Participants n=285 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	119 Participants n=297 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.	232 Participants n=582 Participants • Risk Class I to Risk Class III indicate lower risk; Risk Class IV to V require hospitalization. The number analyzed is different from the overall due to missing values.
Chest Radiographic Score	1.94 units on a scale n=282 Participants • The number analyzed is different from the overall due to missing values.	2.09 units on a scale n=294 Participants • The number analyzed is different from the overall due to missing values.	2.02 units on a scale n=576 Participants • The number analyzed is different from the overall due to missing values.
Chest Radiograph Class No Alveolar Consolidation	15 Participants n=282 Participants • The number analyzed is different from the overall due to missing values.	13 Participants n=294 Participants • The number analyzed is different from the overall due to missing values.	28 Participants n=576 Participants • The number analyzed is different from the overall due to missing values.

Serious adverse events
Measure	Arm 1: Inactive Substance n=287 participants at risk Inactive substance Methylprednisolone: Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).	Arm 2: Methylprednisolone n=297 participants at risk Methylprednisolone Methylprednisolone: Methylprednisolone will be given in a double-blind fashion for 20 full days. The treatment course includes a bolus dose on the day of randomization, 7 days of full dose (40 mg/day), 7 days of half dose (20 mg/day), and 6 days of tapering doses (12 mg/day and 4 mg/day).
Vascular disorders Aortic stenosis	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Arterial thrombosis	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Arteriosclerosis	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Deep vein thrombosis	0.70% 2/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Dry gangrene	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Haematoma	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Hypertension	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Hypertensive crisis	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Hypertensive emergency	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Hypotension	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Orthostatic hypotension	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	1.0% 3/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Vascular disorders Shock	0.70% 2/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Blood and lymphatic system disorders Anaemia	1.7% 5/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	1.3% 4/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Blood and lymphatic system disorders Blood disorder	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Blood and lymphatic system disorders Haemorrhagic disorder	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.67% 2/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Acute myocardial infarction	2.1% 6/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.67% 2/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Angina pectoris	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Angina unstable	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Aortic valve stenosis	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Atrial fibrillation	1.7% 5/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	1.3% 4/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Atrial flutter	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Atrioventricular block complete	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Bradycardia	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Cardiac arrest	0.70% 2/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Cardiac failure	1.7% 5/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Cardiac failure congestive	6.3% 18/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	8.4% 25/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Cardiac tamponade	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Cardiomyopathy	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Cardio-respiratory arrest	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Chordae tendinae rupture	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Conduction disorder	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Coronary artery disease	0.70% 2/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Coronary artery occlusion	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Coronary artery stenosis	0.70% 2/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Ischaemic cardiomyopathy	0.35% 1/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.00% 0/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Palpitations	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Pulseless electrical activity	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.
Cardiac disorders Supraventricular tachycardia	0.00% 0/287 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.	0.34% 1/297 • All SAEs were reported from Randomization to day 180. We did not collect data on non-serious adverse events.