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

• ClinicalTrials.gov Identifier: NCT00852397
• Recruitment Status: Terminated
• First Posted: February 27, 2009
• Results First Posted: August 29, 2013
• Last Update Posted: August 29, 2013
• Sponsor: Pfizer
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Acute Coronary Syndrome	Drug: Apixaban; Other: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 151 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, 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)
• Study Start Date: April 2009
• Actual Primary Completion Date: December 2010
• Actual Study Completion Date: December 2010

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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 :

1. Percentage of Participants Who Had One or More All Bleeding Occurring During the Treatment Period. [ Time Frame: Week 0 to Week 24 ]
   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.
2. 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 ]
   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.
3. 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 ]
   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).
4. 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 ]
5. 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]) ]
   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:

1. 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 ]

   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.

2. 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 ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ogawa H, Goto S, Matsuzaki M, Hiro S, Shima D; APPRAISE-J investigators. Randomized, double-blind trial to evaluate the safety of apixaban with antiplatelet therapy after acute coronary syndrome in Japanese patients (APPRAISE-J). Circ J. 2013;77(9):2341-8. Epub 2013 Jun 7.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00852397
• Other Study ID Numbers: B0661004
• First Posted: February 27, 2009
• Results First Posted: August 29, 2013
• Last Update Posted: August 29, 2013
• Last Verified: August 2013

Additional relevant MeSH terms:

Acute Coronary Syndrome; Syndrome; Disease; Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Apixaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants