Efficacy and Safety Study of Apixaban for Extended Treatment of Deep Vein Thrombosis or Pulmonary Embolism

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00633893
First received: March 5, 2008
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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)


Condition Intervention Phase
Venous Thrombosis
Drug: Apixaban
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Safety and Efficacy Trial Evaluating the Use of Apixaban for the Extended Treatment of Deep Vein Thrombosis and Pulmonary Embolism

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Adjudicated Composite of Symptomatic, Recurrent Venous Thromboembolism (VTE) or All-Cause Death During the Intended Treatment Period - Randomized Population With Imputation [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 months ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Adjudicated Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or VTE-related Death During the Intended Treatment Period - Randomized Population With Imputation [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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 Composite of Recurrent, Symptomatic Venous Thromboembolism (VTE) or Cardio Vascular (CV) -Related Death During the Intended Treatment Period - Randomized Population With Imputation [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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.

  • Adjudicated Nonfatal Deep Vein Thrombosis (DVT) During the Intended Treatment Period - Randomized Population With Imputation [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 12 months ] [ Designated as safety issue: Yes ]
    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 Clinically Relevant Minor Bleeding During the Treatment Period - Treated Participants [ Time Frame: Day 1 up to 12 months ] [ Designated as safety issue: Yes ]
    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 Total Bleeding During the Treatment Period - Treated Participants [ Time Frame: Day 1 up to 12 months ] [ Designated as safety issue: Yes ]
    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 Venous Thromboembolism-related Death During the Intended Treatment Period - Randomized Population Without Imputation [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Day 1 up to 12 Months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 2711
Study Start Date: May 2008
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
2.5 mg
Drug: Apixaban
Tablets, Oral, twice daily, 12 months
Other Name: BMS-562247
Experimental: 2
5.0 mg
Drug: Apixaban
Tablets, Oral, twice daily, 12 months
Other Name: BMS-562247
Active Comparator: 3
0 mg
Drug: Placebo
Tablets, Oral, twice daily, 12 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00633893

  Show 429 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Pfizer
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided by Bristol-Myers Squibb

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00633893     History of Changes
Other Study ID Numbers: CV185-057, EUDRACT: 2007-004953-27
Study First Received: March 5, 2008
Results First Received: August 19, 2013
Last Updated: October 30, 2013
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration
Canada: Health Canada
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Brazil: National Health Surveillance Agency
Chile: Instituto de Salud Pública de Chile
Mexico: Federal Commission for Sanitary Risks Protection
Austria: Federal Office for Safety in Health Care
Denmark: Danish Medicines Agency
France: Ministry of Health
Germany: Ministry of Health
Israel: Ministry of Health
Italy: Ministry of Health
Norway: Directorate of Health
Spain: Spanish Agency of Medicines
South Africa: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: Ministry of Health
Hungary: Ministry of Health, Social and Family Affairs
Poland: Ministry of Health
Russia: Ministry of Health of the Russian Federation
Ukraine: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Hong Kong: Department of Health
India: Central Drugs Standard Control Organization
Korea: Food and Drug Administration
Malaysia: National Pharmaceutical Control Bureau
Taiwan: Department of Health
Romania: National Medicines Agency
Portugal: National Pharmacy and Medicines Institute

Additional relevant MeSH terms:
Thrombosis
Pulmonary Embolism
Venous Thrombosis
Venous Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Embolism
Thromboembolism

ClinicalTrials.gov processed this record on September 30, 2014