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

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

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)

Study Overview

• Status: Completed
• Conditions: Deep Vein Thrombosis; Pulmonary Embolism
• Intervention / Treatment: Drug: Apixaban; Drug: Unfractionated Heparin (UFH); Drug: Warfarin

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University Hospital
  • Kumamoto, Japan, 861-4193
    • Saiseikai Kumamoto Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Aichi
    • Nagakute, Aichi, Japan, 480-1195
      • Aichi Medical University Hospital
  • Chiba
    • Sakura, Chiba, Japan, 285-8741
      • Toho University Sakura Medical Center
  • Fukuoka
    • Kitakyusyu, Fukuoka, Japan, 802-8555
      • Kokura Memorial Hospital
  • Hiroshima
    • Hatsukaichi, Hiroshima, Japan, 738-8503
      • Hiroshima General Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 006-8555
      • Teine Keijinkai Hospital
  • Ishikawa
    • Kahoku-gun, Ishikawa, Japan, 920-0293
      • Kanazawa Medical University Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 245-8575
      • National Hospital Organization Yokohama Medical Center
    • Yokohama, Kanagawa, Japan, 236-0037
      • Yokohama Minami Kyousai Hospital
  • MIE
    • Tsu, MIE, Japan, 514-8507
      • Mie University Hospital
  • Okayama
    • Okayama City, Okayama, Japan, 701-1192
      • National Hospital Organization Okayama Medical Center
  • Osaka
    • Osakasayama, Osaka, Japan, 589-8511
      • Kinki University Hospital
    • Suita-shi, Osaka, Japan, 565-8565
      • National Cerebral and Cardiovascular Center Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-8560
      • St. Luke's International Hospital
    • Itabashi-ku, Tokyo, Japan, 173-8610
      • Nihon University Itabashi Hospital
    • Meguro-ku, Tokyo, Japan, 152-8902
      • National Hospital Organization Tokyo Medical Center
    • Musashino, Tokyo, Japan, 180-8610
      • Japanese Red Cross Musashino Hospital
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pfizer
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: January 29, 2013
• First Submitted That Met QC Criteria: January 29, 2013
• First Posted (Estimate): January 31, 2013

Study Record Updates

• Last Update Posted (Estimate): June 23, 2016
• Last Update Submitted That Met QC Criteria: May 16, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: PE; DVT; VTE
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Heparin; Apixaban; Calcium heparin; Warfarin
• Other Study ID Numbers: B0661024; CV185160 (Other Identifier: BMS)