AStudy To Evaluate Safety And Eficacy Of Apixaban In Japanese Acute Deep Vein Thrombosis (DVT) And Pulmonary Embolism (PE) Patients

Study Overview
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Brief Summary
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The purpose of this study is to investigate safety of apixaban in Japanese acute DVT/PE subjects when symptomatic DVT/PE subjects are treated with 10 mg BID apixaban for 7 days as initial therapy followed by 5 mg BID apixaban for 23 weeks as long-term therapy (total treatment period is 24 weeks)

Official Title
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Active-control, Multicenter, Randomized, Open-label, Safety And Efficacy Study Evaluating The Use Of Apixaban In The Treatment Of Symptomatic Deep Vein Thrombosis And Pulmonary Embolism In Japanese

Conditions
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Deep Vein Thrombosis, Pulmonary Embolism

Intervention / Treatment
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* Drug: Apixaban
* Drug: Unfractionated Heparin (UFH)
* Drug: Warfarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute symptomatic proximal DVT with evidence of proximal thrombosis Acute symptomatic PE with evidence of thrombosis in segmental or more proximal branches Exclusion Criteria: Active bleeding or high risk for bleeding contraindicating treatment with UFH and a VKA. Uncontrolled hypertension: systolic blood pressure > 180 mm Hg or diastolic blood pressure > 110 mm Hg Subjects requiring dual anti-platelet therapy

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban<br> | Drug: Apixaban<br>* 10 mg BID for 7 days followed by 5 mg BID for 23 weeks (total 24 weeks)<br>|
| Active Comparator: UFH/Warfarin<br> | Drug: Unfractionated Heparin (UFH)<br>* Dosing adjustment based on APTT = 1.5-2.5 times the control value, and until INR ≥ 1.5 for 5 days or more<br>Drug: Warfarin<br>* Dosing for 24 weeks to target INR range between 1.5-2.5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Major Bleeding Events ［Per International Society on Thrombosis and Homeostasis (ISTH) Definition］ or Clinically Relevant Non-major (CRNM) Bleeding Events Adjudicated by Clinical Event Committee During the Treatment Period | Major bleeding event was defined as an acute clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more, a transfusion of 4 or more units of packed red blood cells (a unit of packed red blood cells equal to about 200 cc), or bleeding that occurred in critical sites (e.g. intracranial). Fatal bleeding was also defined as a major bleeding event. CRNM bleeding event was defined as an acute clinically overt bleeding that did not satisfy the definition of major bleeding and that led to either hospitalization, physician guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adjudicated Recurrent Symptomatic Venous Thromboembolism (VTE) ［Nonfatal Deep Venous Thrombosis (DVT) or Nonfatal Pulmonary Embolism (PE)］ or VTE-Related Death During the Intended Treatment Period | VTE-related death was defined as a death caused by documented PE which was diagnosed with objective testing or autopsy, or an unexplained death for which DVT/PE could not be ruled out as the cause. Intended Treatment Period was the period starting on the day of randomization and ending at either 2 days after the last dose of the study drug or Day 168/Week 24, whichever came late. | Baseline to Week 24 | 
| Number of Participants With Adjudicated Thrombotic Burden Worsened in Acute Symptomatic Proximal Deep Venous Thrombosis (DVT) | Computed tomography venography (CTV) and compression ultrasound (CUS) were used to assess thrombotic burden in the participants with DVT and the results were classified as improved, no change, or worsened. The timings of CTV and CUS examinations were at Week 12 and Weeks 2, 12 and 24. | Baseline to Week 24 | 
| Number of Participants With Adjudicated Thrombotic Burden Worsened in Acute Symptomatic Pulmonary Embolism (PE) | Computed tomography pulmonary angiography (CTPA) was used to assess thrombotic burden in the participants with PE and the results were classified as improved, no change, or worsened. The timings of CTPA examinations were Weeks 2, 12 and 24. | Baseline to Week 24 | 
| Number of Participants With Adjudicated Major Bleeding Events ［Per International Society on Thrombosis and Homeostasis (ISTH) Definition］During the Treatment Period | Major bleeding event was defined as an acute clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more, a transfusion of 4 or more units of packed red blood cells (a unit of packed red blood cells equal to about 200 cc), or bleeding that occurred in critical sites (e.g. intracranial). Fatal bleeding was also defined as a major bleeding event. | Baseline to Week 24 | 
| Number of Participants With Adjudicated All Bleeding Events During the Treatment Periods | All bleeding events consisted of major bleeding (per Interactional Society on Thrombosis and Homeostasis ［ISTH］ Definition), clinically relevant non-major (CRNM) and minor bleeding. All acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRMN bleeding were classified as minor bleeding. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DVT, PE, VTE