Venous Thrombosis
Conditions
Brief summary
The purpose is to evaluate the effects of an investigational blood thinner, apixaban, in preventing venous thromboembolic (VTE) recurrence or death in patients who have completed their intended treatment for deep vein thrombosis (DVT) or pulmonary embolism (PE)
Interventions
DRUGApixaban
Tablets, Oral, twice daily, 12 months
DRUGPlacebo
Tablets, Oral, twice daily, 12 months
Sponsors
Pfizer
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥ 18 years of age; * Clinical diagnosis of Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE); * Anticoagulant treatment completed * No recurrence of Venous Thromboembolism (VTE)
Exclusion criteria
* Subjects with indications for long-term treatment with a vitamin K antagonist * Active bleeding or high risk for serious bleeding * Short life expectancy * Uncontrolled high blood pressure * Impaired kidney or liver function
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event. |
| Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 months | VTE included: nonfatal DVT or nonfatal PE. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | VTE-related death defined as: PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). |
| Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Day 1 up to 12 Months | All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. First event category was the first primary event for each participant and each participant was counted once. CV-related death was presented excluding VTE-related death. In participants with event category, each participant was counted once in each event category but could have been counted in multiple categories. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. |
| Adjudicated Major Bleeding During the Treatment Period - Treated Population | Day 1 up to 12 Months | Major bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ; or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | Day 1 up to 12 Months | Major bleeding and clinically relevant non-major bleeding were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Major bleeding was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | Day 1 up to 12 months | Non-major clinically relevant bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and defined as: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding (or lasting more than 5 minutes); spontaneous hematuria (macroscopic or lasted more than 24 hours after instrumentation of the urogenital tract); macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis (if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. |
| Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event. |
| Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants | Day 1 up to 12 months | All bleeding events were reviewed by the central independent adjudication committee blinded to treatment and classified as major bleeding, clinically relevant non-major bleeding, minor bleeding or no bleeding. If event was not major or clinically relevant non-major, it was judged to be minor. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints. |
| Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event. Index events of DVT and/or PE, along with myocardial infarction and stroke were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. |
| Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint. |
| Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and these were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | Day 1 up to 12 Months | DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted. |
| Adjudicated Total Bleeding During the Treatment Period - Treated Participants | Day 1 up to 12 months | All bleeding events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug. |
| Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation | Day 1 up to 12 Months | VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Composite endpoint included events that occurred any time from randomization until end of the intended treatment period, regardless of whether the participants were receiving drug treatment. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. If there were missing endpoint data, participants were imputed as having had an efficacy outcome event. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Hong Kong, India, Israel, Italy, Mexico, Norway, Philippines, Poland, Portugal, Puerto Rico, Romania, Russia, Singapore, South Africa, South Korea, Spain, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
First participant, first visit: 16 May 2008; Last participant, last visit: 24 August 2012.
Pre-assignment details
2711 enrolled/2482 randomized: 133 did not meet inclusion, exclusion criteria; 48 withdrew consent; 8 non-compliance; 3 each administrative and clinical reasons; 2 lost to follow up; 1 death; 1 adverse event (AE), 30 other. Data from 4 participants in site 0650 not analyzed/included in randomized population because source for data not confirmed.
Participants by arm
| Arm | Count |
|---|---|
| Apixaban 2.5 mg Participants received 2.5 mg oral tablet apixaban BID. | 840 |
| Apixaban 5 mg Participants received 5 mg oral tablet apixaban BID. | 813 |
| Placebo Participants received matching placebo oral tablet BID. | 829 |
| Total | 2,482 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 65 | 58 | 126 |
| Overall Study | Death | 1 | 3 | 9 |
| Overall Study | Lost to Follow-up | 2 | 4 | 8 |
| Overall Study | Not meet/no longer meets criteria | 4 | 6 | 4 |
| Overall Study | Other | 28 | 33 | 31 |
| Overall Study | Poor/non-compliance | 5 | 12 | 3 |
| Overall Study | Pregnancy | 2 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 12 | 6 |
Baseline characteristics
| Characteristic | Total | Apixaban 2.5 mg | Apixaban 5 mg | Placebo |
|---|---|---|---|---|
| Age Continuous | 56.7 years STANDARD_DEVIATION 15.4 | 56.6 years STANDARD_DEVIATION 15.3 | 56.4 years STANDARD_DEVIATION 15.6 | 57.1 years STANDARD_DEVIATION 15.2 |
| Index Event Classification PE | 860 participants | 296 participants | 286 participants | 278 participants |
| Index Event Classification Proximal DVT | 1622 participants | 544 participants | 527 participants | 551 participants |
| Region of Enrollment Argentina | 22 participants | 7 participants | 9 participants | 6 participants |
| Region of Enrollment Australia | 89 participants | 30 participants | 28 participants | 31 participants |
| Region of Enrollment Austria | 31 participants | 12 participants | 8 participants | 11 participants |
| Region of Enrollment Brazil | 73 participants | 19 participants | 24 participants | 30 participants |
| Region of Enrollment Canada | 54 participants | 22 participants | 17 participants | 15 participants |
| Region of Enrollment Chile | 5 participants | 2 participants | 1 participants | 2 participants |
| Region of Enrollment Czech Republic | 140 participants | 43 participants | 49 participants | 48 participants |
| Region of Enrollment Denmark | 147 participants | 47 participants | 58 participants | 42 participants |
| Region of Enrollment France | 165 participants | 60 participants | 55 participants | 50 participants |
| Region of Enrollment Germany | 177 participants | 62 participants | 55 participants | 60 participants |
| Region of Enrollment Hong Kong | 11 participants | 4 participants | 3 participants | 4 participants |
| Region of Enrollment India | 71 participants | 24 participants | 23 participants | 24 participants |
| Region of Enrollment Israel | 102 participants | 34 participants | 34 participants | 34 participants |
| Region of Enrollment Italy | 193 participants | 67 participants | 65 participants | 61 participants |
| Region of Enrollment Korea, Republic of | 9 participants | 4 participants | 3 participants | 2 participants |
| Region of Enrollment Mexico | 62 participants | 22 participants | 18 participants | 22 participants |
| Region of Enrollment Norway | 28 participants | 9 participants | 9 participants | 10 participants |
| Region of Enrollment Philippines | 11 participants | 5 participants | 3 participants | 3 participants |
| Region of Enrollment Poland | 137 participants | 45 participants | 44 participants | 48 participants |
| Region of Enrollment Portugal | 2 participants | 1 participants | 1 participants | 0 participants |
| Region of Enrollment Romania | 20 participants | 6 participants | 7 participants | 7 participants |
| Region of Enrollment Russian Federation | 140 participants | 45 participants | 49 participants | 46 participants |
| Region of Enrollment Singapore | 6 participants | 1 participants | 2 participants | 3 participants |
| Region of Enrollment South Africa | 106 participants | 34 participants | 42 participants | 30 participants |
| Region of Enrollment Spain | 78 participants | 27 participants | 25 participants | 26 participants |
| Region of Enrollment Ukraine | 252 participants | 87 participants | 77 participants | 88 participants |
| Region of Enrollment United Kingdom | 92 participants | 33 participants | 29 participants | 30 participants |
| Region of Enrollment United States | 259 participants | 88 participants | 75 participants | 96 participants |
| Sex: Female, Male Female | 1058 Participants | 353 Participants | 344 Participants | 361 Participants |
| Sex: Female, Male Male | 1424 Participants | 487 Participants | 469 Participants | 468 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 341 / 840 | 305 / 811 | 318 / 826 |
| serious Total, serious adverse events | 112 / 840 | 107 / 811 | 158 / 826 |
Outcome results
Primary
Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation
VTE included: nonfatal deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE). All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=32, 34, 96 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively; number of events imputed=13, 20, 19, respectively. Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0381 Proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0418 Proportion of participants |
| Placebo | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | 0.1158 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced VTE/all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.p-value: <0.000195% CI: [0.2225, 0.4844]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced VTE/all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat principle.p-value: <0.000195% CI: [0.2475, 0.5281]Cochran-Mantel-Haenszel
Primary
Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation
VTE included: nonfatal DVT or nonfatal PE. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted. Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.
Time frame: Day 1 up to 12 months
Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned.(n)number of events = 19, 14, 77 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. All events were counted; no events were imputed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0226 Proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0172 Proportion of participants |
| Placebo | Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0929 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.p-value: <0.000195% CI: [0.1476, 0.3975]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/all cause mortality to proportion of placebo participants with VTE/all cause mortality equal to 1.0. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.p-value: <0.000195% CI: [0.1062, 0.3261]Cochran-Mantel-Haenszel
Secondary
Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation
DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. (n) number of events = 22, 25, 33 in apixaban 2.5 mg, apixaban 5 mg, and placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0262 Proportion of participants |
| Apixaban 5 mg | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0308 Proportion of participants |
| Placebo | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0398 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with all cause mortality to proportion of placebo participants with all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.236195% CI: [0.3874, 1.1169]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with all cause mortality to proportion of placebo participants with all cause mortality equal to 1.0. Participants with missing data were assumed to have experienced all cause mortality. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.315595% CI: [0.4631, 1.2832]Cochran-Mantel-Haenszel
Secondary
Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation
DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 7, 4, 14 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0083 Proportion of participants |
| Apixaban 5 mg | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0049 Proportion of participants |
| Placebo | Adjudicated All-Cause Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0169 Proportion of participants |
Secondary
Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation
CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. number of events (n)= 17, 24, 29 in the apixaban 2.5 mg, 5 mg, placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0202 Proportion of Participants |
| Apixaban 5 mg | Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0295 Proportion of Participants |
| Placebo | Adjudicated Cardiovascular (CV)-Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0350 Proportion of Participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with CV-related death to proportion of placebo participants with CV-related death equal to 1.0. Participants with missing data were assumed to have experienced CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.131695% CI: [0.3215, 1.0443]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with CV-related death to proportion of placebo participants with CV-related death equal to 1.0. Participants with missing data were assumed to have experienced CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.528895% CI: [0.4959, 1.4341]Cochran-Mantel-Haenszel
Secondary
Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation
CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event and these were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 10 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0024 Proportion of participants |
| Apixaban 5 mg | Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0037 Proportion of participants |
| Placebo | Adjudicated Cardio Vascular (CV)-Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0121 Proportion of participants |
Secondary
Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants
All bleeding events were reviewed by the central independent adjudication committee blinded to treatment and classified as major bleeding, clinically relevant non-major bleeding, minor bleeding or no bleeding. If event was not major or clinically relevant non-major, it was judged to be minor. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time frame: Day 1 up to 12 months
Population: Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 75, 98, 58 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants | 0.0893 Proportion of participants |
| Apixaban 5 mg | Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants | 0.1208 Proportion of participants |
| Placebo | Adjudicated Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants | 0.0702 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with minor bleeding to proportion of placebo participants with minor bleeding equal to 1.0.p-value: 0.169195% CI: [0.9064, 1.7457]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with minor bleeding to proportion of placebo participants with minor bleeding equal to 1.0.p-value: 0.001395% CI: [1.2468, 2.3102]Cochran-Mantel-Haenszel
Secondary
Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants
Non-major clinically relevant bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and defined as: acute clinically overt bleeding compromising hemodynamics; leading to hospitalization; traumatic subcutaneous hematoma; intramuscular hematoma; epistaxis that lasted for more than 5 minutes, was repetitive or led to an intervention; spontaneous gingival bleeding (or lasting more than 5 minutes); spontaneous hematuria (macroscopic or lasted more than 24 hours after instrumentation of the urogenital tract); macroscopic gastrointestinal hemorrhage (including at least 1 episode of melena or hematemesis (if clinically apparent with positive results on a fecal occult-blood test); rectal blood loss. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time frame: Day 1 up to 12 months
Population: Treated population includes randomized participants who received at least one dose of study drug. (n)number of events = 25, 34, 19 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | 0.0298 Proportion of participants |
| Apixaban 5 mg | Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | 0.0419 Proportion of participants |
| Placebo | Adjudicated Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | 0.0230 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with clinically relevant non-major bleeding to proportion of placebo participants with clinically relevant non-major bleeding equal to 1.0.p-value: 0.393295% CI: [0.7158, 2.3348]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with clinically relevant non-major bleeding to proportion of placebo participants with clinically relevant non-major bleeding equal to 1.0.p-value: 0.062195% CI: [1.047, 3.176]Cochran-Mantel-Haenszel
Secondary
Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants
Major bleeding and clinically relevant non-major bleeding were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Major bleeding was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 mL or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time frame: Day 1 up to 12 Months
Population: Treated participants were those who received at least 1 dose of study drug. (n)number of events = 27, 35, 22 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | 0.0321 proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | 0.0432 proportion of participants |
| Placebo | Adjudicated Composite of Major/Clinically Relevant Non-major Bleeding During the Treatment Period - Treated Participants | 0.0266 proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with major/clinically relevant non-major bleeding to proportion of placebo participants with major/clinically relevant non-major bleeding equal to 1.0.p-value: 0.514895% CI: [0.6897, 2.0975]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with major/clinically relevant non-major bleeding to proportion of placebo participants with major/clinically relevant non-major bleeding equal to 1.0.p-value: 0.141295% CI: [0.9554, 2.7336]Cochran-Mantel-Haenszel
Secondary
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation
VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Composite endpoint included events that occurred any time from randomization until end of the intended treatment period, regardless of whether the participants were receiving drug treatment. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. If there were missing endpoint data, participants were imputed as having had an efficacy outcome event.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with consent.(n)number of events=27, 34, 95 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. The (n)number of imputed events were = 13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0321 proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0418 proportion of participants |
| Placebo | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.1146 proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/CV-related death to proportion of placebo participants with VTE/CV-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: <0.000195% CI: [0.1844, 0.4247]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/CV-related death to proportion of placebo participants with VTE/CV-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/CV-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: <0.000195% CI: [0.25, 0.5338]Cochran-Mantel-Haenszel
Secondary
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation
CV-related death was defined as myocardial infarction, stroke, or other specified cardiovascular event. Index events of DVT and/or PE, along with myocardial infarction and stroke were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 76 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0167 proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0172 proportion of participants |
| Placebo | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) - Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0917 proportion of participants |
Secondary
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation
VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for these endpoints.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 14, 14, 73 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0167 proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0172 proportion of participants |
| Placebo | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0881 proportion of participants |
Secondary
Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation
VTE includes nonfatal DVT or nonfatal PE. All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate (proportion of participants with event) calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Composite endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. For missing endpoint data, participants were imputed as having had a primary efficacy outcome event.
Time frame: Day 1 up to 12 Months
Population: ITT: all randomized participants with consent. Analyzed per randomized treatment assigned. (n) number of events=27, 34, 92 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. Number of imputed events=13, 20, 19 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0321 Proportion of participants |
| Apixaban 5 mg | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0418 Proportion of participants |
| Placebo | Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.1110 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/VTE-related death to proportion of placebo participants with VTE/ VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/ VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: <0.000195% CI: [0.1902, 0.4395]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE/VTE-related death to proportion of placebo participants with VTE/ VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE/ VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: <0.000195% CI: [0.2577, 0.5525]Cochran-Mantel-Haenszel
Secondary
Adjudicated Major Bleeding During the Treatment Period - Treated Population
Major bleeding was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was defined as acute clinically overt bleeding: associated with a fall in hemoglobin of 2 grams per deciliter (g/dL) or more, or leading to a transfusion of 2 or more units of packed red blood cells or 1000 milliliters (mL) or more of whole blood, or in a critical site: intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or another critical organ; or is fatal. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Confidence interval (CI) for event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time frame: Day 1 up to 12 Months
Population: Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 2, 1, 4 in apixaban 2.5 mg, and 5 mg, and placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Major Bleeding During the Treatment Period - Treated Population | 0.0024 Proportion of participants |
| Apixaban 5 mg | Adjudicated Major Bleeding During the Treatment Period - Treated Population | 0.0012 Proportion of participants |
| Placebo | Adjudicated Major Bleeding During the Treatment Period - Treated Population | 0.0048 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with major bleeding to proportion of placebo participants with major bleeding equal to 1.0. Treated participants with at least one dose of study drug were included.p-value: 0.392595% CI: [0.0891, 2.6391]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with major bleeding to proportion of placebo participants with major bleeding equal to 1.0. Participants treated with at least one dose of study drug were included.p-value: 0.355195% CI: [0.0269, 2.2437]Cochran-Mantel-Haenszel
Secondary
Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation
DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period: longer of the dosing period plus 2 days (completed treatment) or 355 days (discontinued early). Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). Confidence interval (CI) for single event rate was calculated based on the Wald asymptotic confidence limits.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 19, 28, 72 in apixaban 2.5 mg, 5 mg, placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation | 0.0226 Proportion of participants |
| Apixaban 5 mg | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation | 0.0344 Proportion of participants |
| Placebo | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation | 0.0869 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with nonfatal DVT to proportion of placebo participants with nonfatal DVT equal to 1.0. Participants with missing data were assumed to have experienced nonfatal DVT. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, Intent to treat (ITT) principle.p-value: <0.000195% CI: [0.1593, 0.4292]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with nonfatal DVT to proportion of placebo participants with nonfatal DVT equal to 1.0. Participants with missing data were assumed to have experienced nonfatal DVT. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: <0.000195% CI: [0.2595, 0.6079]Cochran-Mantel-Haenszel
Secondary
Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation
DVT was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 6, 8, 53 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation | 0.0071 proportion of participants |
| Apixaban 5 mg | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation | 0.0098 proportion of participants |
| Placebo | Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population Without Imputation | 0.0639 proportion of participants |
Secondary
Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation
PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment and was assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. Participants with missing endpoint information were classified as having had the efficacy event (imputation). CI for single event rate was calculated based on the Wald asymptotic confidence limits.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 23, 25, 37 in apixaban 2.5 mg, 5 mg, placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation | 0.0274 Proportion of participants |
| Apixaban 5 mg | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation | 0.0308 Proportion of participants |
| Placebo | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population With Imputation | 0.0446 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with nonfatal PE to proportion of placebo participants with nonfatal PE equal to 1.0. Participants with missing data were assumed to have experienced nonfatal PE. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.108495% CI: [0.3653, 1.0145]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with nonfatal PE to proportion of placebo participants with nonfatal PE equal to 1.0. Participants with missing data were assumed to have experienced nonfatal PE. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.132995% CI: [0.4164, 1.1257]Cochran-Mantel-Haenszel
Secondary
Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation
PE was adjudicated/confirmed by a central independent adjudication committee blinded to treatment: PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint; participants who had an event during the intended treatment period were counted.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 8, 4, 15 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation | 0.0095 Proportion of participants |
| Apixaban 5 mg | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation | 0.0049 Proportion of participants |
| Placebo | Adjudicated Nonfatal Pulmonary Embolism (PE) During the Intended Treatment Period - Randomized Population Without Imputation | 0.0181 Proportion of participants |
Secondary
Adjudicated Total Bleeding During the Treatment Period - Treated Participants
All bleeding events were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). CI for single event rate was calculated based on the Wald asymptotic confidence limits. Treated population includes randomized participants who received at least one dose of study drug.
Time frame: Day 1 up to 12 months
Population: Treated population includes randomized participants who received at least one dose of study drug. (n) number of events = 94, 121, 74 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Total Bleeding During the Treatment Period - Treated Participants | 0.1119 Proportion of participants |
| Apixaban 5 mg | Adjudicated Total Bleeding During the Treatment Period - Treated Participants | 0.1492 Proportion of participants |
| Placebo | Adjudicated Total Bleeding During the Treatment Period - Treated Participants | 0.0896 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with total bleeding to proportion of placebo participants with total bleeding equal to 1.0. Total bleeding was defined as any major, clinically relevant non-major, or minor bleeding.p-value: 0.146695% CI: [0.9276, 1.6507]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with total bleeding to proportion of placebo participants with total bleeding equal to 1.0. Total bleeding is any major, clinically relevant non-major, or minor bleeding.p-value: 0.000595% CI: [1.2552, 2.1606]Cochran-Mantel-Haenszel
Secondary
Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation
VTE-related death defined as: PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, death, venous/arterial thromboembolic events, bleeding, thrombocytopenia, acute myocardial infarction and stroke were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Participants with missing endpoint information were classified as having had the efficacy event (imputation).
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. (n) number of events = 17, 24, 26 in apixaban 2.5 mg, 5 mg, placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0202 Proportion of participants |
| Apixaban 5 mg | Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0295 Proportion of participants |
| Placebo | Adjudicated Venous Thromboembolism (VTE) - Related Death During the Intended Treatment Period - Randomized Population With Imputation | 0.0314 Proportion of participants |
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE-related death to proportion of placebo participants with VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.305995% CI: [0.3543, 1.1813]Cochran-Mantel-Haenszel
Comparison: Null hypothesis is relative risk proportion of apixaban participants with VTE-related death to proportion of placebo participants with VTE-related death equal to 1.0. Participants with missing data were assumed to have experienced VTE-related death. Events occurring anytime during the intended treatment period (12 months) were included regardless of whether the participant was on treatment or not or whether the participant ever took drug, ie, ITT principle.p-value: 0.828895% CI: [0.5458, 1.6245]Cochran-Mantel-Haenszel
Secondary
Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation
VTE related death defined as PE (based on objective diagnostic testing, autopsy), unexplained death (and VTE cannot be ruled out), sudden death (and VTE cannot be ruled out). DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment: DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. New/recurrent VTE, and death, were also adjudicated. Event rate is proportion of participants with event; calculated as n/N (n=number of events; N=number of participants). Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. No imputation was done for this endpoint.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Participants analyzed per randomized treatment assigned. (n) number of events = 2, 3, 7 in apixaban 2.5 mg, 5 mg, and placebo arms, respectively. CI for single event rate was calculated based on the Wald asymptotic confidence limits.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Apixaban 2.5 mg | Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0024 Proportion of participants |
| Apixaban 5 mg | Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0037 Proportion of participants |
| Placebo | Adjudicated Venous Thromboembolism (VTE)- Related Death During the Intended Treatment Period - Randomized Population Without Imputation | 0.0084 Proportion of participants |
Secondary
Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation
All index events, DVT and/or PE were adjudicated/confirmed by a central independent adjudication committee blinded to treatment. DVT assessed by compression ultrasound and/or venography; PE assessed by spiral computed tomography scanning, pulmonary angiography, and/or ventilation/perfusion lung scan. Intended treatment period was defined as the longer of the dosing period plus 2 days or 355 days. Endpoint included events at any time from randomization until end of the intended treatment period, regardless whether drug treatment was received. First event category was the first primary event for each participant and each participant was counted once. CV-related death was presented excluding VTE-related death. In participants with event category, each participant was counted once in each event category but could have been counted in multiple categories. No imputation was done for these endpoints; participants who had an event during the intended treatment period were counted.
Time frame: Day 1 up to 12 Months
Population: Intent to treat: all randomized participants with valid consent. Analyzed per randomized treatment assigned. In first event (first primary event) each participant counted once. In event category, each participant was counted only once in each event category but could have been counted in multiple categories.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | VTE-related Death (included in all-cause total) | 2 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: nonfatal DVT | 6 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: nonfatal PE | 8 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: Participants with nonfatal PE | 7 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: Participants with nonfatal DVT | 6 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: All-Cause Death | 6 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | CV-related Death (included in all-cause total) | 0 participants |
| Apixaban 2.5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: All cause death | 7 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | VTE-related Death (included in all-cause total) | 3 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | CV-related Death (included in all-cause total) | 0 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: nonfatal DVT | 8 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: All-Cause Death | 3 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: nonfatal PE | 4 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: Participants with nonfatal DVT | 7 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: All cause death | 4 participants |
| Apixaban 5 mg | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: Participants with nonfatal PE | 4 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: All cause death | 14 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: nonfatal DVT | 53 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: Participants with nonfatal DVT | 53 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: Participants with nonfatal PE | 13 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | First event: All-Cause Death | 11 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | CV-related Death (included in all-cause total) | 3 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | Participants with event: nonfatal PE | 15 participants |
| Placebo | Number of Participants With an Adjudicated Symptomatic Nonfatal Venous Thromboembolism (VTE) Recurrence or Death (All Cause) During the Intended Treatment Period - Randomized Participants Without Imputation | VTE-related Death (included in all-cause total) | 7 participants |