A Study to Evaluate the Safety of Apixaban in Acute Coronary Syndrome (ACS) Japanese Patients

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00852397
First received: February 26, 2009
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to assess the bleeding safety (the composite endpoint of major and clinically relevant non-major bleeding) of 2 doses of apixaban (2.5 mg BID and 5.0 mg BID) or placebo in combination with standard therapy (aspirin and /or additional antiplatelet therapy) over a 24 week treatment period in selected subjects with recent (≤7 days) acute coronary syndrome.


Condition Intervention Phase
Acute Coronary Syndrome
Drug: Apixaban
Other: Placebo
Phase 2

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 Phase 2, Placebo-Controlled, Randomized, Double-Blinded, Multicenter, Study To Evaluate The Bleeding Profile Of 2.5 Mg And 5.0 Mg BID Apixaban In Combination With Standard Therapy In Patients With Recent (≤7 Days) Acute Coronary Syndrome (ACS)

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Who Had Composite of International Society on Thrombosis and Haemostasis (ISTH)-Defined Major and Clinically-relevant Non-major (CRNM) Bleeding Events Occurring During the Treatment Period. [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: Yes ]
    Major bleeding event was acute clinically overt bleeding accompanied by decrease in hemoglobin of 2 g/dL or more over a 24-hour period, transfusion of 2 or more units of packed red blood cells, or bleeding that occurs in critical site (e.g., intracranial). Fatal bleeding was also major bleeding event. CRNM bleeding was acute or sub-acute clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy.


Secondary Outcome Measures:
  • Percentage of Participants Who Had One or More All Bleeding Occurring During the Treatment Period. [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: Yes ]
    All bleeding included major bleeding (including fatal bleeding), clinically-relevant non-major (CRNM) bleeding, and minor bleeding per international society on thrombosis and haemostasis (ISTH) definitions.

  • Percentage of Participants Who Had Major Bleeding Occurring During the Treatment Period Per International Society on Thrombosis and Haemostasis (ISTH) Definitions. [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: Yes ]
    Major bleeding event was defined as an acute clinically overt bleeding accompanied by decrease in hemoglobin of 2 g/dL or more over a 24-hour period, transfusion of 2 or more units of packed red blood cells, or bleeding that occured in critical site (e.g., intracranial). Fatal bleeding was also major bleeding event.

  • Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI)-Defined Major Bleeding Occurring During the Treatment Period. [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: Yes ]
    TIMI major bleeding event was difined as an intracranial bleeding or clinically overt bleeding (including bleeding evident on imaging studies) associated with a >= 5 gm/dL fall in hemoglobin or a 15% fall in hematocrit from baseline, accounting for the effect of transfusions (1 unit packed red blood cells = 1 gm/dL hemoglobin = 3% hematocrit).

  • Percentage of Participants Who Had Composite of All-cause Death, Non-fatal Myocardial Infarction, Unstable Angina and Stroke During 30 Days After Discontinuation of Therapy. [ Time Frame: For 30 days after Week 24 or the discontinuation of study drug ] [ Designated as safety issue: Yes ]
  • Percentage of Participants Who Had Composite of All-cause Death, Non-fatal Myocardial Infarction (MI), Unstable Angina, and Non-hemorrhagic Stroke Occurring During the Intended Treatment Period. [ Time Frame: From the day of randomization to the later date of either 2-days after the last dose of study drug or Day 168/Week 24 after randomization day (or the study termination date [19 November 2010, Japan time]) ] [ Designated as safety issue: No ]
    Intended treatment period for efficacy endpoints was defined as a period starting on the day of randomization and ending at the later date of either 2-days after the last dose of study drug or Day 168/Week 24 after randomization day (or the study termination date [19 November 2010, Japan time]).


Other Outcome Measures:
  • Percentage of Participants Who Had International Society on Thrombosis and Haemostasis (ISTH)-Defined Individual Bleeding Endpoints (Clinically-relevant Non-major [CRNM] or Minor Bleeding) During the Treatment Period. [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: Yes ]

    ISTH-defined CRNM bleeding was defined as an acute or sub-acute clinically overt bleeding that did not satisfy the criteria for major bleeding and that led to either hospital admission for bleeding, physician guided medical or surgical treatment for bleeding or a change in antithrombotic therapy.

    ISTH defined minor bleeding event was defined as all acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRNM bleeding were classified as minor bleeding.


  • Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI) Defined-individual Bleeding Endpoints (Minor or Minimal Bleeding) During the Treatment Period. [ Time Frame: Week 0 to Week 24 ] [ Designated as safety issue: Yes ]

    TIMI minor bleeding event was defined as a clinically overt bleeding (including bleeding evident on imaging studies) associated with a >= 3 gm/dL fall in hemoglobin or a 9% fall in hematocrit from baseline, accounting for the effect of transfusions (1 unit packed red blood cells = 1 gm/dL hemoglobin = 3% hematocrit).

    TIMI minimal bleeding event was defined as a clinically overt bleeding (including bleeding evident on imaging studies) not meeting criteria for TIMI minor bleeding.



Enrollment: 151
Study Start Date: April 2009
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Apixaban 2.5 mg Drug: Apixaban
Apixaban 2.5 mg tablet BID for 24 weeks
Experimental: Apixaban 5.0 mg Drug: Apixaban
Apixaban 5.0 mg tablet BID for 24 weeks
Placebo Comparator: Placebo Other: Placebo
Placebo tablet for 24 weeks

Detailed Description:

Due to withdraw of global phase 3 study (APPRAISE-2) for safety issue, B0661004 Data monitoring committee (DMC) also recommended terminating this study. Therefore, Pfizer decided to stop this study.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Recent (≤ 7 days) ACS
  • Clinically stable, and receiving standard treatment (patients must be treated with aspirin ≤ 100 mg/day, with or without clopidogrel 75 mg/day or ticlopidine 200 mg/day) based on the physician's judgment)

Exclusion Criteria:

  • Scheduled/planned cardiac catheterization, PCI, CABG or other invasive procedure planned in the 24 weeks (within treatment period) following randomization
  • Persistent severe hypertension, defined as systolic blood pressure of ≥180 mm Hg or diastolic pressure of ≥110 mm Hg
  • Active bleeding or at high risk for bleeding (e.g., cirrhosis of the liver, any history of intracranial hemorrhage).
  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: NCT00852397

Locations
Japan
Pfizer Investigational Site
Kasuga, Fukuoka, Japan
Pfizer Investigational Site
Kitakyusyu, Fukuoka, Japan
Pfizer Investigational Site
Kure, Hiroshima, Japan
Pfizer Investigational Site
Sapporo, Hokkaido, Japan
Pfizer Investigational Site
Uji, Kyoto, Japan
Pfizer Investigational Site
Ikoma, Nara, Japan
Pfizer Investigational Site
Hirakata, Osaka, Japan
Pfizer Investigational Site
Kawachinagano, Osaka, Japan
Pfizer Investigational Site
Matsubara, Osaka, Japan
Pfizer Investigational Site
Yao, Osaka, Japan
Pfizer Investigational Site
Wako, Saitama, Japan
Pfizer Investigational Site
Sunto, Shizuoka, Japan
Pfizer Investigational Site
Minato-Ku, Tokyo, Japan
Pfizer Investigational Site
Shinagawa, Tokyo, Japan
Pfizer Investigational Site
Gifu, Japan
Pfizer Investigational Site
Hiroshima, Japan
Pfizer Investigational Site
Kumamoto, Japan
Pfizer Investigational Site
Osaka, Japan
Sponsors and Collaborators
Pfizer
Bristol-Myers Squibb
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00852397     History of Changes
Other Study ID Numbers: B0661004
Study First Received: February 26, 2009
Results First Received: June 4, 2013
Last Updated: August 27, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Additional relevant MeSH terms:
Acute Coronary Syndrome
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Angina Pectoris
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms

ClinicalTrials.gov processed this record on August 01, 2014