Safety Study of Apixaban in Recent Acute Coronary Syndrome

Acute Coronary Syndrome (ACS) Clinical Trial

Official title:

A Phase 2, Placebo-Controlled, Randomized, Double Blind, Parallel Arm, Dose Ranging Study to Evaluate Safety and Efficacy of Apixaban in Patients With a Recent Acute Coronary Syndrome.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00313300
• Other study ID #: CV185-023
• Status: Completed
• Phase: Phase 2
• First received: April 10, 2006
• Last updated: November 25, 2015
• Start date: May 2006
• Est. completion date: May 2008

Study information

• Verified date: November 2015
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to determine whether apixaban will be safe in people who have recently had unstable angina or a heart attack.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1741
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

Key Inclusion Criteria:

• Recent (< = 7 days) Acute Coronary Syndrome (ACS).

• Clinically stable on optimal treatment

Key Exclusion Criteria:

• High bleeding risk.

• Ongoing anticoagulant use.

• Need for chronic (>3 months) daily nonsteroidal anti-inflammatory drug (NSAID) or chronic high dose acetylsalicylic acid (ASA) use (>325 mg/day

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndrome (ACS)
• Syndrome

Intervention

Drug:
• Apixaban
Tablets, Oral, 2.5 mg, twice daily, 26 weeks
• Apixaban
Tablets, Oral, 10 mg, once daily, 26 weeks
• Placebo
Tablets, Oral, 0, twice daily, 26 weeks
• Apixaban
Tablets, Oral 10 mg, twice daily, 26 weeks

Locations

Country	Name	City	State
Austria	Local Institution	Feldkirch
Austria	Local Institution	Wien
Austria	Local Institution	Wien
Belgium	Local Institution	Aalst
Belgium	Local Institution	Antwerpen
Belgium	Local Institution	Brasschaat
Belgium	Local Institution	Brugge
Belgium	Local Institution	Brussels
Belgium	Local Institution	Genk
Belgium	Local Institution	Huy	Luik
Canada	Local Institution	Belleville	Ontario
Canada	Local Institution	Chatham	Ontario
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Edmonton	Alberta
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	London	Ontario
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Oshawa	Ontario
Canada	Local Institution	St. Charles-Borromee	Quebec
Canada	Local Institution	St. John'S	Newfoundland and Labrador
Canada	Local Institution	Terrebonne	Quebec
Canada	Local Institution	Victoria	British Columbia
Denmark	Local Institution	Arhus C
Denmark	Local Institution	Copenhagen
Denmark	Local Institution	Esbjerg
Denmark	Local Institution	Frederiksberg
Denmark	Local Institution	Glostrup
Denmark	Local Institution	Hellerup
Denmark	Local Institution	Herning
Denmark	Local Institution	Randers
France	Local Institution	Amiens Cedex 1
France	Local Institution	Cholet
France	Local Institution	Dijon
France	Local Institution	Nantes Cedex 01
France	Local Institution	Paris Cedex 13
France	Local Institution	Pessac Cedex
France	Local Institution	Roubaix Cedex 1
France	Local Institution	Toulouse
Germany	Local Institution	Berlin
Germany	Local Institution	Berlin
Germany	Local Institution	Duren
Germany	Local Institution	Halle / Saale
Germany	Local Institution	Hannover
Germany	Local Institution	Krefeld
Germany	Local Institution	Langen
Germany	Local Institution	Ludwigshafen
Germany	Local Institution	Witten
Israel	Local Institution	Afula
Israel	Local Institution	Hadera
Israel	Local Institution	Haifa
Israel	Local Institution	Haifa
Israel	Local Institution	Jerusalem
Israel	Local Institution	Jerusalem
Israel	Local Institution	Jerusalem
Israel	Local Institution	Kfar-Saba
Israel	Local Institution	Nazareth
Israel	Local Institution	Petach Tikva
Israel	Local Institution	Rehovot
Israel	Local Institution	Safed
Israel	Local Institution	Tel Aviv
Italy	Local Institution	Roma
Poland	Local Institution	Bialystok
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Bydgoszcz
Poland	Local Institution	Cracow
Poland	Local Institution	Gdansk
Poland	Local Institution	Katowice
Poland	Local Institution	Krakow
Poland	Local Institution	Lodz
Poland	Local Institution	Opole
Poland	Local Institution	Torun
Poland	Local Institution	Warszawa
Poland	Local Institution	Zielona Gora
Russian Federation	Local Institution	Kemerovo
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Moscow
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saint Petersburg
Russian Federation	Local Institution	Saratov
Russian Federation	Local Institution	St. Petersburg
Russian Federation	Local Institution	St.Petersburg
Russian Federation	Local Institution	Yaroslav
Russian Federation	Local Institution	Yaroslavl
Spain	Local Institution	Baracaldo (Vizcaya)
Spain	Local Institution	Barcelona
Spain	Local Institution	Hospitalet Llobregat Barcelona
Spain	Local Institution	Leon
Spain	Local Institution	Madrid
Spain	Local Institution	Malaga
Spain	Local Institution	Oviedo
Spain	Local Institution	Santiago De Compostela
Spain	Local Institution	Sevilla
Spain	Local Institution	Tarragona
Spain	Local Institution	Valladolid
Spain	Local Institution	Villajoyosa
Sweden	Local Institution	Goteborg
Sweden	Local Institution	Goteborg
Sweden	Local Institution	Malmo
Sweden	Local Institution	Orebro
Sweden	Local Institution	Stockholm
Sweden	Local Institution	Sundsvall
Sweden	Local Institution	Uppsala
United Kingdom	Local Institution	Croydon
United Kingdom	Local Institution	Edinburgh	Midlothian
United Kingdom	Local Institution	Harrow	Middlesex
United Kingdom	Local Institution	Leicester
United Kingdom	Local Institution	Portadown	N. Ireland
United Kingdom	Local Institution	Sheffield	South Yorkshire
United Kingdom	Local Institution	Stockport	Cheshire
United Kingdom	Local Institution	York	Yorkshire
United States	Cardiac Disease Specialists, P.C.	Atlanta	Georgia
United States	Unc Hospitals, Department Of Medicine	Chapel Hill	North Carolina
United States	Midwest Cardiology Research Foundation	Columbus	Ohio
United States	Georgia Heart Specialists	Covington	Georgia
United States	Geisinger Clinic - Cardiology	Danville	Pennsylvania
United States	The Dayton Heart Center	Dayton	Ohio
United States	Iowa Heart Center	Des Moines	Iowa
United States	Dumc	Durham	North Carolina
United States	Carolina Heart Specialists	Gastonia	North Carolina
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Piedmont Cardiology Associates	Hickory	North Carolina
United States	The Care Group, Llc.	Indianapolis	Indiana
United States	Cardiovascular Associates, P.C	Kingsport	Tennessee
United States	Watson Clinic Center For Research	Lakeland	Florida
United States	University Of Kentucky	Lexington	Kentucky
United States	South Denver Cardiology Associates	Littleton	Colorado
United States	Los Angeles County & University Of Southern Ca. Medical Cen.	Los Angeles	California
United States	New York Cardiovascular Associates	New York	New York
United States	Oklahoma Cardiovascular Research Group	Oklahoma City	Oklahoma
United States	Heartcare Midwest	Peoria	Illinois
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Heart & Vasc Inst Of Fl	Safety Harbor	Florida
United States	University Of Texas Medical School - San Antonio	San Antonio	Texas
United States	Radiant Research,Santa Rosa	Santa Rosa	California
United States	Scottsdale Cardiovasular Research Institute	Scottsdale	Arizona
United States	William Beaumont Hospital-Troy	Troy	Michigan
United States	Tyler Cardiovascular Consultants	Tyler	Texas
United States	Indian River Medical Center	Vero Beach	Florida
United States	Wake Forest Univ Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Denmark,  France,  Germany,  Israel,  Italy,  Poland,  Russian Federation,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses	Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The primary outcome is based on data for the placebo and 2 apixaban low-dose groups (2.5 mg BID and 10 mg QD) combined across Phase A and Phase B. The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups (10mg BID, 20mg QD) and the resulting lower duration of exposure for these groups.	From first dose of study drug (Day 1) to last dose plus 2 days, up to Year 2 of the Study	Yes
Secondary	Number of Participants With a Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants	Events were adjudicated by the Clinical Events Committee (CEC). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B.	Randomization to 182 days after randomization (183 days)	No
Secondary	Event Rate for Adjudicated All Bleeding Events During the Treatment Period - Treated Participants With Placebo or Apixaban Low Doses	Bleeding was assessed using the International Society on Thrombosis and Hemostasis (ISTH) guidelines. Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events includes major bleeding, clinically relevant non-major bleeding and minor bleeding. Treatment Period refers to the period from first dose through 2 days, or through 30 days for Serious Adverse Event (SAE) tabulations, after discontinuation of study drug. Data in this outcome are combined across Phase A and Phase B.	first dose (Day 1) to last dose plus 2 days (or for SAEs, plus 30 days), up to Year 2 of the Study	Yes
Secondary	Number of Participants With a Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, and Non-Hemorrhagic Stroke During the Intended Treatment Period - Randomized Participants	Events were adjudicated by the Clinical Events Committee (CEC). Event rate was number of participants with events divided by the number of participants treated (%). Intended Treatment Period refers to the period starting on the day of randomization and ending 182 days after the day of randomization (for a total period duration of 183 days). Data in this outcome are combined across Phase A and Phase B	Day of randomization to 182 days after day of randomization (183 days)	No
Secondary	Event Rate of Confirmed Adjudicated Major Bleeding During the Treatment Period- Treated Participants With Placebo or Apixaban Low Doses	Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the Clinical Events Committee. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%).	from first dose (Day 1) to last dose plus 2 days, up to Year 2 of the Study	Yes
Secondary	Number of Participants With Composite of Adjudicated All-Cause Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B	Phase B Adjusted Intended Treatment Period=day of randomization and ends on termination date of high dose apixaban, 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.	Day of randomization and ends on high dose termination date, 1-Oct-2007	No
Secondary	Event Rate of Composite of Adjudicated Major Bleeding and Clinically Relevant Non-Major Bleeding During the Phase B Adjusted Treatment Period- Treated Participants Randomized in Phase B	Bleeding was assessed using ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated, measured as a percentage (%). The analyses of Phase B data across all doses of apixaban are secondary because of the premature termination of the apixaban high-dose groups and the lower duration of exposure. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).	From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007	Yes
Secondary	Event Rate for Adjudicated All Bleeding Events During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B	Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%). All bleeding events included major bleeding, clinically relevant non-major bleeding and minor bleeding. Phase B Adjusted Treatment Period=safety events occurring in the period from first dose through 2 days (or through 30 days for SAE tabulations) after the earliest of last dose date or 1-Oct-2007 (termination date for the 10 mg BID group).	From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007	Yes
Secondary	Number of Participants With Composite of Adjudicated Cardiovascular Death, Non-Fatal Myocardial Infarction, Severe Recurrent Ischemia, Non-Hemorrhagic Stroke During the Phase B Adjusted Intended Treatment Period - Participants Randomized in Phase B	Phase B Adjusted Intended Treatment Period=day of randomization and ends on 1-Oct-2007. The analyses of Phase B data across all doses of apixaban are secondary due to the premature termination of the apixaban high dose groups and the lower duration of exposure.	Day of randomization up to high dose termination, 1-Oct-2007	No
Secondary	Event Rate of Confirmed Adjudicated Major Bleeding During the Phase B Adjusted Treatment Period - Treated Participants Randomized in Phase B	Bleeding was assessed using the ISTH guidelines. Events were adjudicated by the CEC. Event rate was number of participants with events divided by the number of participants treated (%).	From first dose (Day 1) to last dose, plus 2 days (plus 30 days for SAEs), up to high dose termination, 1 October 2007	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm