Trial Outcomes & Findings for Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation (NCT NCT00412984)

Last Updated: 2018-07-03

Results Overview

All suspected efficacy events were adjudicated by the Central Events Committee (CEC). Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

20976 participants

Primary outcome timeframe

Time to first event in "Intended Treatment Period": started on day of randomization, ended at efficacy cut-off date (date target number of primary efficacy events [448] was expected to have occurred; set to 30-Jan-2011, prior to unblinding).

Results posted on

2018-07-03

Participant Flow

20998 participants were enrolled, and 18201 were randomized.

Participant milestones

Participant milestones
Measure	Apixaban Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Overall Study STARTED	9120	9081
Overall Study COMPLETED	6810	6588
Overall Study NOT COMPLETED	2310	2493

Reasons for withdrawal

Reasons for withdrawal
Measure	Apixaban Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Overall Study Death	331	349
Overall Study Adverse Event	679	738
Overall Study Withdrawal by Subject	921	989
Overall Study Lost to Follow-up	51	39
Overall Study Poor/Noncompliance	57	77
Overall Study Pregnancy	1	0
Overall Study Subject No Longer Meets Study Criteria	87	100
Overall Study Administrative Reason by Sponsor	11	8
Overall Study Physician Refused to Continue Treatment	81	89
Overall Study Other Reason	80	92
Overall Study Not Reported	11	12

Baseline Characteristics

Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.	Total n=18201 Participants Total of all reporting groups
Age, Continuous	69.1 years STANDARD_DEVIATION 9.61 • n=5 Participants	69.0 years STANDARD_DEVIATION 9.74 • n=7 Participants	69.1 years STANDARD_DEVIATION 9.68 • n=5 Participants
Age, Customized <65 years	2731 Participants n=5 Participants	2740 Participants n=7 Participants	5471 Participants n=5 Participants
Age, Customized Between 65 and 75 years	3539 Participants n=5 Participants	3513 Participants n=7 Participants	7052 Participants n=5 Participants
Age, Customized >=75 years	2850 Participants n=5 Participants	2828 Participants n=7 Participants	5678 Participants n=5 Participants
Sex: Female, Male Female	3234 Participants n=5 Participants	3182 Participants n=7 Participants	6416 Participants n=5 Participants
Sex: Female, Male Male	5886 Participants n=5 Participants	5899 Participants n=7 Participants	11785 Participants n=5 Participants
Race/Ethnicity, Customized White (European)	5440 Participants n=5 Participants	5366 Participants n=7 Participants	10806 Participants n=5 Participants
Race/Ethnicity, Customized White (Middle Eastern or North African)	59 Participants n=5 Participants	66 Participants n=7 Participants	125 Participants n=5 Participants
Race/Ethnicity, Customized White (Other White)	2037 Participants n=5 Participants	2060 Participants n=7 Participants	4097 Participants n=5 Participants
Race/Ethnicity, Customized White (Not Reported)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Black / African American	125 Participants n=5 Participants	102 Participants n=7 Participants	227 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Asian Indian)	307 Participants n=5 Participants	312 Participants n=7 Participants	619 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Chinese)	536 Participants n=5 Participants	536 Participants n=7 Participants	1072 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Japanese)	164 Participants n=5 Participants	180 Participants n=7 Participants	344 Participants n=5 Participants
Race/Ethnicity, Customized Asian (Other Asian)	303 Participants n=5 Participants	304 Participants n=7 Participants	607 Participants n=5 Participants
Race/Ethnicity, Customized American Indian / Alaska Native	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian / Other Pacific Islander	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Other	121 Participants n=5 Participants	127 Participants n=7 Participants	248 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic / Latino	1808 Participants n=5 Participants	1803 Participants n=7 Participants	3611 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic / Latino	7312 Participants n=5 Participants	7276 Participants n=7 Participants	14588 Participants n=5 Participants
Female Age Category <=50 years	81 Participants n=5 Participants	88 Participants n=7 Participants	169 Participants n=5 Participants
Female Age Category >50 years	3153 Participants n=5 Participants	3094 Participants n=7 Participants	6247 Participants n=5 Participants
Female Age Category not applicable (male)	5886 Participants n=5 Participants	5899 Participants n=7 Participants	11785 Participants n=5 Participants
Apixaban/Matching Placebo Dose at Randomization 2.5 mg twice daily (BID)	428 Participants n=5 Participants	403 Participants n=7 Participants	831 Participants n=5 Participants
Apixaban/Matching Placebo Dose at Randomization 5.0 mg BID	8692 Participants n=5 Participants	8678 Participants n=7 Participants	17370 Participants n=5 Participants
Risk Factor at Enrollment: Age >= 75 Years >=75 years	2850 Participants n=5 Participants	2828 Participants n=7 Participants	5678 Participants n=5 Participants
Risk Factor at Enrollment: Age >= 75 Years <75 years	6270 Participants n=5 Participants	6253 Participants n=7 Participants	12523 Participants n=5 Participants
Risk Factor at Enrollment: Prior Stroke With prior stroke	1045 Participants n=5 Participants	1082 Participants n=7 Participants	2127 Participants n=5 Participants
Risk Factor at Enrollment: Prior Stroke Prior stroke not a risk factor	8075 Participants n=5 Participants	7999 Participants n=7 Participants	16074 Participants n=5 Participants
Risk Factor at Enrollment: Prior Transient Ischemic Attack (TIA) With prior TIA	603 Participants n=5 Participants	654 Participants n=7 Participants	1257 Participants n=5 Participants
Risk Factor at Enrollment: Prior Transient Ischemic Attack (TIA) Prior TIA not a risk factor	8517 Participants n=5 Participants	8427 Participants n=7 Participants	16944 Participants n=5 Participants
Risk Factor At Enrollment: Symptomatic Chronic Heart Failure (CHF) With symptomatic CHF	2784 Participants n=5 Participants	2757 Participants n=7 Participants	5541 Participants n=5 Participants
Risk Factor At Enrollment: Symptomatic Chronic Heart Failure (CHF) Symptomatic CHF not a risk factor	6336 Participants n=5 Participants	6324 Participants n=7 Participants	12660 Participants n=5 Participants
Risk Factor at Enrollment: Left Ventricle Ejection Fraction (LVEF) <=40% With LVEF <=40%	1324 Participants n=5 Participants	1301 Participants n=7 Participants	2625 Participants n=5 Participants
Risk Factor at Enrollment: Left Ventricle Ejection Fraction (LVEF) <=40% LVEF <=40% not a risk factor	7796 Participants n=5 Participants	7780 Participants n=7 Participants	15576 Participants n=5 Participants
Number of Risk Factors <= 1	3025 Participants n=5 Participants	3000 Participants n=7 Participants	6025 Participants n=5 Participants
Number of Risk Factors >= 2	6095 Participants n=5 Participants	6081 Participants n=7 Participants	12176 Participants n=5 Participants
CHADS-2 Score at Enrollment Score of <= 1	3100 Participants n=5 Participants	3083 Participants n=7 Participants	6183 Participants n=5 Participants
CHADS-2 Score at Enrollment Score of 2	3262 Participants n=5 Participants	3254 Participants n=7 Participants	6516 Participants n=5 Participants
CHADS-2 Score at Enrollment Score of >= 3	2758 Participants n=5 Participants	2744 Participants n=7 Participants	5502 Participants n=5 Participants
Mean CHADS-2 Score at Enrollment	2.1 units on a scale STANDARD_DEVIATION 1.10 • n=5 Participants	2.1 units on a scale STANDARD_DEVIATION 1.11 • n=7 Participants	2.1 units on a scale STANDARD_DEVIATION 2.10 • n=5 Participants

PRIMARY outcome

Timeframe: Time to first event in "Intended Treatment Period": started on day of randomization, ended at efficacy cut-off date (date target number of primary efficacy events [448] was expected to have occurred; set to 30-Jan-2011, prior to unblinding).

Population: Intention to treat analysis, randomized participants. Participants who did not experience an efficacy endpoint event were censored at the earlier of their death date (when death is not part of the endpoint), last contact date (for subjects who withdrew consent to be followed up or were lost to follow-up) or the efficacy cut-off date (30-Jan-2011).

Outcome measures

Outcome measures
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period Ischemic or Unspecified Stroke	159 participants	173 participants
Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period Hemorrhagic Stroke	38 participants	76 participants
Number of Participants With First Event of Ischemic/Unspecified Stroke, Hemorrhagic Stroke, or Systemic Embolism (SE) During the Intended Treatment Period Systemic Embolism	15 participants	16 participants

PRIMARY outcome

Timeframe: "Intended Treatment Period" started on the day of randomization and ended at the efficacy cut-off date (date on which it was expected that the target number of primary efficacy events [448] would have occurred; set to 30-Jan-2011, prior to unblinding).

Rate=Number of adjudicated stroke or SE events per 100 patient years. Diagnosis of stroke=the nontraumatic focal neurological deficit lasting at least 24 hours, and includes ischemic stroke, hemorrhagic stroke, ischemic stroke with hemorrhagic conversion, stroke of uncertain type, and retinal ischemic event (embolism, infarction). Diagnosis of SE=clinical history consistent with an acute loss of blood flow to a peripheral artery (or arteries), supported by evidence of embolism from surgical specimens, autopsy, angiography, vascular imaging, or other objective testing.

Outcome measures

Outcome measures
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Adjudicated Stroke or Systemic Embolism (SE) During the Intended Treatment Period	1.27 Number of events per 100 patient years	1.60 Number of events per 100 patient years

SECONDARY outcome

Timeframe: "Treatment Period" started with first dose of blinded study drug and ended 2 days after the last dose of blinded study drug. Mean duration of exposure to double-blind study drug was 1.7 years in each treatment group.

Population: Treated participants. Participants who did not experience a bleeding endpoint were censored at the earlier of 2 days after discontinuation of study drug, or death date, or last-contact date (for participants who withdrew consent to be followed up or were lost to follow-up) at the end of the study.

ISTH Bleeding Criteria: Major bleeding=a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more, and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following critical sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With Event of Major (International Society on Thrombosis and Hemostasis [ISTH]) Bleeding During Treatment Period	327 participants	462 participants

SECONDARY outcome

Rate=number of adjudicated major (ISTH) bleed events per 100 patient years. ISTH Bleeding Criteria: Major bleeding=a bleeding event that was: clinically overt bleeding accompanied by a decrease in hemoglobin (Hgb) of 2 g/dL or more and/or a transfusion of 2 or more units of packed red blood cells; bleeding that occurred in at least 1 of the following sites: intracranial, intraspinal, intraocular (within the corpus of the eye; a conjunctival bleed is not an intraocular bleed), pericardial, intra-articular, intramuscular with compartment syndrome, and retroperitoneal; bleeding that was fatal.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Adjudicated Major (ISTH) Bleed Events During Treatment Period	2.13 Number of events per 100 patient years	3.09 Number of events per 100 patient years

SECONDARY outcome

Death was defined as all-cause mortality. All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided. Cardiovascular=deaths due to ischemic and hemorrhagic stroke, SE, myocardial infarction (MI), sudden death, heart failure, other cardiovascular, and unobserved deaths. Non-cardiovascular=all deaths due to a clearly documented non-cardiovascular cause (further classified into the categories: bleeding, study drug toxicity other than bleeding, malignancy, infection, trauma, and pulmonary causes of death).

Outcome measures

Outcome measures
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With Events of All-Cause Death During the Intended Treatment Period	603 participants	669 participants

SECONDARY outcome

All unobserved deaths were assumed to be cardiovascular in nature unless a non-cardiovascular cause could be clearly provided. Cardiovascular=deaths due to ischemic and hemorrhagic stroke, SE, MI, sudden death, heart failure, other cardiovascular, and unobserved deaths. Non-cardiovascular=all deaths due to a clearly documented non-cardiovascular cause (further classified into the categories: bleeding, study drug toxicity other than bleeding, malignancy, infection, trauma, and pulmonary causes of death).

Outcome measures

Outcome measures
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Adjudicated All-Cause Death During the Intended Treatment Period	3.52 Number of events per 100 patient years	3.94 Number of events per 100 patient years

SECONDARY outcome

Population: Intention to treat analysis, randomized participants. Participants who did not experience an efficacy endpoint event were censored at the earlier of their death date (when death is not part of the endpoint), last contact date, or the efficacy cut-off date (30-Jan-2011). n=number of participants experiencing stated event.

Diagnosis for an acute or evolving MI=elevation of creatine kinase-MB isoenzyme (CK-MB) or Troponin T or I ≥ 2 × the upper limit of normal (ULN), or if no CK-MB or troponin values are available, a total CK ≥ 2×ULN, or new, significant (≥0.04 s) Q waves in ≥2 contiguous leads. For descriptions of Stroke and SE, see Outcome Measure 1.

Outcome measures

Outcome measures
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), and Myocardial Infarction (MI) (as Individual Endpoints) During the Intended Treatment Period Hemorrhagic Stroke (n=40, 78)	0.24 Number of events per 100 patient years	0.47 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), and Myocardial Infarction (MI) (as Individual Endpoints) During the Intended Treatment Period Ischemic or Unspecified Stroke (n=162, 175)	0.97 Number of events per 100 patient years	1.05 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), and Myocardial Infarction (MI) (as Individual Endpoints) During the Intended Treatment Period Systemic Embolism (n=15, 17)	0.09 Number of events per 100 patient years	0.10 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), and Myocardial Infarction (MI) (as Individual Endpoints) During the Intended Treatment Period Myocardial Infarction (n=90, 102)	0.53 Number of events per 100 patient years	0.61 Number of events per 100 patient years

SECONDARY outcome

Population: Intention to treat analysis, randomized participants. Participants who didn't experience an efficacy endpoint event were censored at the earlier of their death date (when death is not part of the endpoint), last contact date, or the efficacy cut-off date (30-Jan-2011). n= number of participants experiencing stated combination of events.

Diagnosis for an acute or evolving MI=elevation of CK-MB or Troponin T or I ≥ 2 × the ULN, or if no CK-MB or troponin values are available, a total CK ≥ 2×ULN, or new, significant (≥0.04 s) Q waves in ≥2 contiguous leads. For descriptions of Stroke and SE, see Outcome Measure 1. For description of ACD, see Outcome Measure 5.

Outcome measures

Outcome measures
Measure	Apixaban n=9120 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9081 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period Stroke / SE / Major Bleeding (n=521, 666)	3.17 Number of events per 100 patient years	4.11 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period Stroke / SE / All-Cause Death (ACD) (n=752, 837)	4.49 Number of events per 100 patient years	5.04 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period Stroke / SE / Major Bleeding / ACD (n=1009, 1168)	6.13 Number of events per 100 patient years	7.20 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period Stroke / SE / MI / ACD (n=810, 906)	4.85 Number of events per 100 patient years	5.49 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period Ischemic or Unspecified Stroke / ACD (n=725, 796)	4.32 Number of events per 100 patient years	4.78 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period Hemorrhagic Stroke / ACD (n=622, 703)	3.68 Number of events per 100 patient years	4.20 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period SE / ACD (n=613, 679)	3.63 Number of events per 100 patient years	4.05 Number of events per 100 patient years
Rate of Ischemic or Unspecified Stroke, Hemorrhagic Stroke, Systemic Embolism (SE), Myocardial Infarction (MI) and All-Cause Death (ACD) (as Composite Endpoints) During the Intended Treatment Period MI / ACD (n=663, 740)	3.93 Number of events per 100 patient years	4.43 Number of events per 100 patient years

SECONDARY outcome

Population: Intention to treat analysis, randomized participants who were Warfarin/Vitamin K Antagonist (VKA) naïve (a stratification variable, defined as receiving ≤30 consecutive days of prior warfarin/VKA treatment). Participants not experiencing efficacy endpoint event were censored at earlier of death, last contact, or efficacy cut-off date (30-Jan-2011).

For descriptions of Stroke and SE, see Outcome Measure 1. For description of Major bleeding, see Outcome Measure 3.

Outcome measures

Outcome measures
Measure	Apixaban n=3912 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=3888 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Warfarin/Vitamin K Antagonist (VKA) Naive Participants With Composite Stroke / Systemic Embolism (SE) / Major Bleeding During the Intended Treatment Period	229 participants	285 participants

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Apixaban n=3912 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=3888 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Composite Stroke / Systemic Embolism / Major Bleeding in Warfarin/Vitamin K Antagonist (VKA) Naive Participants During the Intended Treatment Period	3.21 Number of events per 100 patient years	4.06 Number of events per 100 patient years

SECONDARY outcome

Major bleeding=bleeding that is clinically overt and that either resulted in a decrease in hemoglobin of 2 g/dL or more over a 24-hour period, led to a transfusion of 2 or more units of packed red blood cells, occurred in a critical site, or led to death. CRNM bleeding=bleeding that is clinically overt, that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event, that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With Events of Major or Clinically Relevant Nonmajor (CRNM) Bleed During Treatment Period	613 participants	877 participants

SECONDARY outcome

Rate=number of major or CRNM bleed events per 100 patient years. Major=clinically overt and either 1) resulted in a decrease in hemoglobin of 2 g/dL or more, or 2) led to a transfusion of 2 or more units of packed red blood cells, or 3) occurred in a critical site, or 4) led to death. CRNM bleeding=clinically overt, but satisfied no additional criteria required to be adjudicated as a major bleeding event, and led to either 1) hospital admission for bleeding or 2) physician guided medical or surgical treatment for bleeding or 3) a change in antithrombotic therapy.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Events of Major or Clinically Relevant Non-Major (CRNM) Bleed During Treatment Period	4.07 number of events / 100 patient years	6.01 number of events / 100 patient years

SECONDARY outcome

All bleeding events include major bleeding, CRNM bleeding (see Outcome Measure 12 Description for definitions), plus events of minor bleeding and fatal bleeding. Minor bleeding: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding will be classified as minor bleeding. Fatal bleeding is defined as a bleeding event that the Clinical Events Committee determines is the primary cause of death or contributes directly to death.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With All Bleeding Events During Treatment Period	2356 participants	3060 participants

SECONDARY outcome

Rate=number of all bleeding events per 100 patient years. "All bleeding events" include major bleeding, CRNM bleeding (see Outcome Measure 12 Description for definitions), plus events of minor bleeding and fatal bleeding. Minor bleeding: All acute clinically overt bleeding events not meeting the criteria for either major bleeding or clinically relevant non-major bleeding will be classified as minor bleeding. Fatal bleeding is defined as a bleeding event that the Clinical Events Committee determines is the primary cause of death or contributes directly to death.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of All Bleeding Events During Treatment Period	18.08 number of events per 100 patient years	25.82 number of events per 100 patient years

OTHER_PRE_SPECIFIED outcome

AE: all SAEs or AEs with onset from first dose through 2 days (AEs) or 30 days (SAEs) after the last dose of blinded study drug (BSD). SAE: all SAEs with onset from first dose through 30 days after the last dose of BSD. Bleeding AE: all serious or non-serious bleeding-related AEs with onset from first dose through 2 days after the last dose of BSD. Discontinuations due to AE: all SAEs or AEs with onset from first dose of BSD and with action taken=drug discontinued. Deaths: all deaths occurring from first dose through 30 days after the last dose of BSD.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With Adverse Events (AEs), Bleeding AEs, Serious Adverse Events (SAEs), Discontinuations Due to AEs, or Deaths During the Treatment Period SAE	3182 participants	3302 participants
Number of Participants With Adverse Events (AEs), Bleeding AEs, Serious Adverse Events (SAEs), Discontinuations Due to AEs, or Deaths During the Treatment Period AE	7406 participants	7521 participants
Number of Participants With Adverse Events (AEs), Bleeding AEs, Serious Adverse Events (SAEs), Discontinuations Due to AEs, or Deaths During the Treatment Period Bleeding AE	2288 participants	2961 participants
Number of Participants With Adverse Events (AEs), Bleeding AEs, Serious Adverse Events (SAEs), Discontinuations Due to AEs, or Deaths During the Treatment Period Discontinuations due to AE	688 participants	758 participants
Number of Participants With Adverse Events (AEs), Bleeding AEs, Serious Adverse Events (SAEs), Discontinuations Due to AEs, or Deaths During the Treatment Period Deaths	429 participants	468 participants

OTHER_PRE_SPECIFIED outcome

Rate=number of adjudicated GUSTO bleeding events per 100 patient years. GUSTO Bleeding Criteria: GUSTO severe (or life-threatening) bleeding: either intracranial hemorrhage or bleeding that causes hemodynamic compromise and requires intervention. GUSTO moderate bleeding: bleeding that requires blood transfusion but does not result in hemodynamic compromise.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Adjudicated Bleeding Endpoints Per Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) During the Treatment Period Severe (n=80, 172))	0.52 Number of events per 100 patient years	1.13 Number of events per 100 patient years
Rate of Adjudicated Bleeding Endpoints Per Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) During the Treatment Period Severe or Moderate (n=199, 328)	1.29 Number of events per 100 patient years	2.18 Number of events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Rate=number of adjudicated TIMI bleeding events per 100 patient years. TIMI Bleeding Criteria: Major bleeding=Intracranial bleeding and/or clinically overt bleeding associated with ≥5 gm/dL fall in Hgb or 15% fall in hematocrit (Hct) from baseline, accounting for transfusions. Minor bleeding=Clinically overt bleeding associated with ≥3 gm/dL fall in Hgb or a ≥10% fall in Hct from baseline, accounting for transfusions.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Adjudicated Bleeding Endpoints Per Thrombolysis in Myocardial Infarction (TIMI) During the Treatment Period Major (n=148, 256)	0.96 Number of events per 100 patient years	1.69 Number of events per 100 patient years
Rate of Adjudicated Bleeding Endpoints Per Thrombolysis in Myocardial Infarction (TIMI) During the Treatment Period Major or Minor (n=239, 370)	1.55 Number of events per 100 patient years	2.46 Number of events per 100 patient years

OTHER_PRE_SPECIFIED outcome

Net-Clinical Benefit = Composite of stroke, systemic embolism and ISTH major bleeding.

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Number of Participants With Net-Clinical Benefit During Treatment Period	459 participants	608 participants

OTHER_PRE_SPECIFIED outcome

Rate=number of events of net-clinical benefit per 100 patient years. Net-Clinical Benefit = Composite of stroke, systemic embolism and ISTH major bleeding

Outcome measures

Outcome measures
Measure	Apixaban n=9088 Participants Participants received apixaban and warfarin-placebo following randomization during a titration phase using a dosing algorithm for warfarin- placebo; apixaban was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin placebo doses were recommended based upon an algorithm using an encrypted, shammed International Normalized Ratio (INR) procedure to preserve the double blind; however, the final dosing decision rested with the investigator.	Warfarin n=9052 Participants Participants received apixaban-placebo and warfarin following randomization during a titration phase using a dosing algorithm for warfarin; apixaban-placebo was dosed at 5 mg twice daily (BID) \[or 2.5 mg BID in select subjects\]. Subsequent warfarin doses were recommended based upon an algorithm and encrypted INR testing to preserve the double blind; however, the final dosing decision rested with the investigator.
Rate of Net-Clinical Benefit During Treatment Period	3.01 Number of events per 100 patient years	4.09 Number of events per 100 patient years

Adverse Events

Warfarin

Serious events: 3182 serious events

Other events: 3876 other events

Deaths: 0 deaths

Apixaban

Serious events: 3302 serious events

Other events: 4071 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Warfarin n=9088 participants at risk	Apixaban n=9052 participants at risk
Injury, poisoning and procedural complications Contusion	3.3% 299/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.3% 479/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Gastrointestinal disorders Diarrhoea	6.4% 580/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	6.4% 581/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Musculoskeletal and connective tissue disorders Back pain	4.7% 428/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.5% 502/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Respiratory, thoracic and mediastinal disorders Cough	5.4% 493/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.6% 505/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Nervous system disorders Headache	5.3% 480/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.4% 485/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
General disorders Oedema peripheral	6.7% 607/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	7.3% 661/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Nervous system disorders Dizziness	7.2% 654/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	7.8% 702/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Infections and infestations Urinary tract infection	5.2% 471/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.5% 501/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Infections and infestations Nasopharyngitis	8.4% 763/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	8.6% 779/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 444/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.1% 462/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Infections and infestations Bronchitis	5.2% 473/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	5.4% 493/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.4% 583/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	7.0% 633/9052 Treated population (includes all patients who received at least 1 dose of study drug.)
Respiratory, thoracic and mediastinal disorders Epistaxis	6.0% 547/9088 Treated population (includes all patients who received at least 1 dose of study drug.)	7.4% 666/9052 Treated population (includes all patients who received at least 1 dose of study drug.)

Additional Information

BMS Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER