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

February 26, 2009
August 27, 2013
April 2009
December 2010   (final data collection date for primary outcome measure)
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.
Incidence of major bleeding and clinically relevant non-major bleeding evaluated by ISTH criteria during the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00852397 on ClinicalTrials.gov Archive Site
  • 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]).
  • Incidence of all bleeding (major bleeding evaluated by ISTH criteria, clinically relevant non-major bleeding, and minor bleeding) occurring through Week 4 and during the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of all bleeding (major bleeding and minor bleeding evaluated by TIMI criteria) during the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of major bleeding during the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Composite of all-cause death, non-fatal myocardial infarction, severe unstable angina and stroke during 30 days after discontinuation of therapy [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Other safety outcome measures will also be assessed, including serious and non-serious AEs and changes in standard clinical laboratory test results [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Composite of all-cause death, non-fatal myocardial infarction, severe unstable angina, and non-hemorrhagic stroke occurring during the treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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.

Not Provided
 
A Study to Evaluate the Safety of Apixaban in Acute Coronary Syndrome (ACS) Japanese Patients
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)

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Acute Coronary Syndrome
  • Drug: Apixaban
    Apixaban 2.5 mg tablet BID for 24 weeks
  • Drug: Apixaban
    Apixaban 5.0 mg tablet BID for 24 weeks
  • Other: Placebo
    Placebo tablet for 24 weeks
  • Experimental: Apixaban 2.5 mg
    Intervention: Drug: Apixaban
  • Experimental: Apixaban 5.0 mg
    Intervention: Drug: Apixaban
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
151
December 2010
December 2010   (final data collection date for primary outcome measure)

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).
Both
20 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Japan
 
NCT00852397
B0661004
Yes
Pfizer
Pfizer
Bristol-Myers Squibb
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP