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

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Primary Purpose

Status

Terminated

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Apixaban

Placebo

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Apixaban 2.5 mg

Apixaban 5.0 mg

Placebo

Arm Description

Outcomes

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.

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.

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.

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.

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.

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.

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]).

Full Information

NCT ID

NCT00852397

First Posted

February 26, 2009

Last Updated

August 27, 2013

Sponsor

Pfizer

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00852397

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

August 2013

Overall Recruitment Status

Terminated

Why Stopped

See termination reason in detailed description.

Study Start Date

April 2009 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

December 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

Collaborators

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Coronary Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

151 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Apixaban 2.5 mg

Arm Type

Experimental

Arm Title

Apixaban 5.0 mg

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

Apixaban

Intervention Description

Apixaban 2.5 mg tablet BID for 24 weeks

Intervention Type

Drug

Intervention Name(s)

Apixaban

Intervention Description

Apixaban 5.0 mg tablet BID for 24 weeks

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Placebo tablet for 24 weeks

Primary Outcome Measure Information:

Title

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.

Description

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.

Time Frame

Week 0 to Week 24

Secondary Outcome Measure Information:

Title

Percentage of Participants Who Had One or More All Bleeding Occurring During the Treatment Period.

Description

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.

Time Frame

Week 0 to Week 24

Title

Percentage of Participants Who Had Major Bleeding Occurring During the Treatment Period Per International Society on Thrombosis and Haemostasis (ISTH) Definitions.

Description

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.

Time Frame

Week 0 to Week 24

Title

Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI)-Defined Major Bleeding Occurring During the Treatment Period.

Description

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).

Time Frame

Week 0 to Week 24

Title

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

Title

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.

Description

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]).

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])

Other Pre-specified Outcome Measures:

Title

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.

Description

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.

Time Frame

Week 0 to Week 24

Title

Percentage of Participants Who Had Thrombolysis in Myocardial Infarction (TIMI) Defined-individual Bleeding Endpoints (Minor or Minimal Bleeding) During the Treatment Period.

Description

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.

Time Frame

Week 0 to Week 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Accepts Healthy Volunteers

No

Eligibility 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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Pfizer CT.gov Call Center

Organizational Affiliation

Pfizer

Official's Role

Study Director

Facility Information:

Facility Name

Pfizer Investigational Site

City

Kasuga

State/Province

Fukuoka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Kitakyusyu

State/Province

Fukuoka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Kure

State/Province

Hiroshima

Country

Japan

Facility Name

Pfizer Investigational Site

City

Sapporo

State/Province

Hokkaido

Country

Japan

Facility Name

Pfizer Investigational Site

City

Uji

State/Province

Kyoto

Country

Japan

Facility Name

Pfizer Investigational Site

City

Ikoma

State/Province

Nara

Country

Japan

Facility Name

Pfizer Investigational Site

City

Hirakata

State/Province

Osaka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Kawachinagano

State/Province

Osaka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Matsubara

State/Province

Osaka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Yao

State/Province

Osaka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Wako

State/Province

Saitama

Country

Japan

Facility Name

Pfizer Investigational Site

City

Sunto

State/Province

Shizuoka

Country

Japan

Facility Name

Pfizer Investigational Site

City

Minato-Ku

State/Province

Tokyo

Country

Japan

Facility Name

Pfizer Investigational Site

City

Shinagawa

State/Province

Tokyo

Country

Japan

Facility Name

Pfizer Investigational Site

City

Gifu

Country

Japan

Facility Name

Pfizer Investigational Site

City

Hiroshima

Country

Japan

Facility Name

Pfizer Investigational Site

City

Kumamoto

Country

Japan

Facility Name

Pfizer Investigational Site

City

Osaka

Country

Japan

12. IPD Sharing Statement

Citations:

PubMed Identifier

23748920

Citation

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. doi: 10.1253/circj.cj-13-0209. Epub 2013 Jun 7.

Results Reference

derived

Links:

URL

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B0661004&StudyName=A%20study%20to%20evaluate%20the%20safety%20of%20Apixaban%20in%20Acute%20Coronary%20Syndrome%20%28ACS%29%20Japanese%20patients

Description

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

Acute Coronary Syndrome

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial