Safety Study of Apixaban in Recent Acute Coronary Syndrome

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.

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome (ACS)
• Intervention / Treatment: Drug: Apixaban; Drug: Apixaban; Drug: Apixaban; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1741
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Feldkirch, Austria, 6800
    • Local Institution
  • Wien, Austria, 1090
    • Local Institution
  • Wien, Austria, 1160
    • Local Institution
• Belgium
  • Aalst, Belgium, 9300
    • Local Institution
  • Antwerpen, Belgium, 2020
    • Local Institution
  • Brasschaat, Belgium, 2930
    • Local Institution
  • Brugge, Belgium, 8000
    • Local Institution
  • Brussels, Belgium, 1090
    • Local Institution
  • Genk, Belgium, 3600
    • Local Institution
  • Luik
    • Huy, Luik, Belgium, 4500
      • Local Institution
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • Local Institution
    • Edmonton, Alberta, Canada, T5H 3V9
      • Local Institution
    • Edmonton, Alberta, Canada, T6K 4C1
      • Local Institution
  • British Columbia
    • Victoria, British Columbia, Canada, V8R 4R2
      • Local Institution
  • Newfoundland and Labrador
    • St. John'S, Newfoundland and Labrador, Canada, A1B 3V6
      • Local Institution
  • Ontario
    • Belleville, Ontario, Canada, K8N1E6
      • Local Institution
    • Chatham, Ontario, Canada, N7L 1B9
      • Local Institution
    • Hamilton, Ontario, Canada, L8L 2X2
      • Local Institution
    • London, Ontario, Canada, N6A 5A5
      • Local Institution
    • Oshawa, Ontario, Canada, L1H 1B9
      • Local Institution
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • Local Institution
    • Montreal, Quebec, Canada, H1T 2M4
      • Local Institution
    • Montreal, Quebec, Canada, H1T 1C8
      • Local Institution
    • St. Charles-Borromee, Quebec, Canada, J6E 6J2
      • Local Institution
    • Terrebonne, Quebec, Canada, J6V 2H2
      • Local Institution
• Denmark
  • Arhus C, Denmark, 8000
    • Local Institution
  • Copenhagen, Denmark, 2100
    • Local Institution
  • Esbjerg, Denmark, 6700
    • Local Institution
  • Frederiksberg, Denmark, 2000
    • Local Institution
  • Glostrup, Denmark, 2600
    • Local Institution
  • Hellerup, Denmark, 2900
    • Local Institution
  • Herning, Denmark, 7400
    • Local Institution
  • Randers, Denmark, DK-8900
    • Local Institution
• France
  • Amiens Cedex 1, France, 80054
    • Local Institution
  • Cholet, France, 49300
    • Local Institution
  • Dijon, France, 21079
    • Local Institution
  • Nantes Cedex 01, France, 44093
    • Local Institution
  • Paris Cedex 13, France, 75651
    • Local Institution
  • Pessac Cedex, France, 33604
    • Local Institution
  • Roubaix Cedex 1, France, 59056
    • Local Institution
  • Toulouse, France, 31403
    • Local Institution
• Germany
  • Berlin, Germany, 12351
    • Local Institution
  • Berlin, Germany, 12559
    • Local Institution
  • Duren, Germany, 52351
    • Local Institution
  • Halle / Saale, Germany, 06120
    • Local Institution
  • Hannover, Germany, 30625
    • Local Institution
  • Krefeld, Germany, 47805
    • Local Institution
  • Langen, Germany, 63225
    • Local Institution
  • Ludwigshafen, Germany, 67063
    • Local Institution
  • Witten, Germany, 58455
    • Local Institution
• Israel
  • Afula, Israel, 18101
    • Local Institution
  • Hadera, Israel, 38100
    • Local Institution
  • Haifa, Israel, 31096
    • Local Institution
  • Haifa, Israel, 34362
    • Local Institution
  • Jerusalem, Israel, 91120
    • Local Institution
  • Jerusalem, Israel, 91031
    • Local Institution
  • Jerusalem, Israel, 91240
    • Local Institution
  • Kfar-Saba, Israel, 44281
    • Local Institution
  • Nazareth, Israel, 16100
    • Local Institution
  • Petach Tikva, Israel, 49100
    • Local Institution
  • Rehovot, Israel, 76100
    • Local Institution
  • Safed, Israel, 13100
    • Local Institution
  • Tel Aviv, Israel, 64239
    • Local Institution
• Italy
  • Roma, Italy, 00168
    • Local Institution
• Poland
  • Bialystok, Poland, 15-276
    • Local Institution
  • Bydgoszcz, Poland, 85-168
    • Local Institution
  • Bydgoszcz, Poland, 85-094
    • Local Institution
  • Bydgoszcz, Poland, 85-826
    • Local Institution
  • Cracow, Poland, 31-202
    • Local Institution
  • Gdansk, Poland, 80-952
    • Local Institution
  • Katowice, Poland, 40-635
    • Local Institution
  • Krakow, Poland, 31-501
    • Local Institution
  • Lodz, Poland, 91-347
    • Local Institution
  • Opole, Poland, 45-418
    • Local Institution
  • Torun, Poland, 87-100
    • Local Institution
  • Warszawa, Poland, 04-628
    • Local Institution
  • Zielona Gora, Poland, 65-046
    • Local Institution
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • Local Institution
  • Moscow, Russian Federation, 129327
    • Local Institution
  • Moscow, Russian Federation, 105229
    • Local Institution
  • Moscow, Russian Federation, 127473
    • Local Institution
  • Moscow, Russian Federation, 115487
    • Local Institution
  • Moscow, Russian Federation, 121552
    • Local Institution
  • Moscow, Russian Federation, 111020
    • Local Institution
  • Moscow, Russian Federation, 119620
    • Local Institution
  • Saint Petersburg, Russian Federation, 191104
    • Local Institution
  • Saint Petersburg, Russian Federation, 193312
    • Local Institution
  • Saint Petersburg, Russian Federation, 195067
    • Local Institution
  • Saint Petersburg, Russian Federation, 197110
    • Local Institution
  • Saratov, Russian Federation, 410028
    • Local Institution
  • St. Petersburg, Russian Federation, 194156
    • Local Institution
  • St.Petersburg, Russian Federation, 192242
    • Local Institution
  • Yaroslav, Russian Federation, 150062
    • Local Institution
  • Yaroslavl, Russian Federation, 150003
    • Local Institution
• Spain
  • Baracaldo (Vizcaya), Spain, 48903
    • Local Institution
  • Barcelona, Spain, 08035
    • Local Institution
  • Hospitalet Llobregat Barcelona, Spain, 08907
    • Local Institution
  • Leon, Spain, 24071
    • Local Institution
  • Madrid, Spain, 28046
    • Local Institution
  • Malaga, Spain, 29010
    • Local Institution
  • Oviedo, Spain, 33006
    • Local Institution
  • Santiago De Compostela, Spain, 15706
    • Local Institution
  • Sevilla, Spain, 41071
    • Local Institution
  • Tarragona, Spain, 43007
    • Local Institution
  • Valladolid, Spain, 47010
    • Local Institution
  • Villajoyosa, Spain, 03570
    • Local Institution
• Sweden
  • Goteborg, Sweden, 413 45
    • Local Institution
  • Goteborg, Sweden, SE-416 85
    • Local Institution
  • Malmo, Sweden, 205 02
    • Local Institution
  • Orebro, Sweden, 701 85
    • Local Institution
  • Stockholm, Sweden, 141 86
    • Local Institution
  • Sundsvall, Sweden, 851 86
    • Local Institution
  • Uppsala, Sweden, 751 85
    • Local Institution
• United Kingdom
  • Croydon, United Kingdom, CR7 7YE
    • Local Institution
  • Leicester, United Kingdom, LE3 9QP
    • Local Institution
  • Cheshire
    • Stockport, Cheshire, United Kingdom, SK2 7JE
      • Local Institution
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • Local Institution
  • Midlothian
    • Edinburgh, Midlothian, United Kingdom, EH16 4SB
      • Local Institution
  • N. Ireland
    • Portadown, N. Ireland, United Kingdom, BT63 5QQ
      • Local Institution
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Local Institution
  • Yorkshire
    • York, Yorkshire, United Kingdom, YO31 8HE
      • Local Institution
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Scottsdale Cardiovasular Research Institute
  • California
    • Los Angeles, California, United States, 90033
      • Los Angeles County & University Of Southern Ca. Medical Cen.
    • Santa Rosa, California, United States, 95405
      • Radiant Research,Santa Rosa
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology Associates
  • Florida
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Center for Research
    • Safety Harbor, Florida, United States, 34695
      • Heart & Vasc Inst Of Fl
    • Vero Beach, Florida, United States, 32960
      • Indian River Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Cardiac Disease Specialists, P.C.
    • Covington, Georgia, United States, 30014
      • Georgia Heart Specialists
  • Illinois
    • Peoria, Illinois, United States, 61614
      • HeartCare Midwest
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • The Care Group, Llc.
  • Iowa
    • Des Moines, Iowa, United States, 50314
      • Iowa Heart Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Michigan
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital-Troy
  • New York
    • New York, New York, United States, 10001
      • New York Cardiovascular Associates
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Unc Hospitals, Department Of Medicine
    • Durham, North Carolina, United States, 27705
      • DUMC
    • Gastonia, North Carolina, United States, 28054
      • Carolina Heart Specialists
    • Hickory, North Carolina, United States, 28602
      • Piedmont Cardiology Associates
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Univ Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43214
      • MidWest Cardiology Research Foundation
    • Dayton, Ohio, United States, 45414
      • The Dayton Heart Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Oklahoma Cardiovascular Research Group
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Clinic - Cardiology
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Cardiovascular Associates, P.C
  • Texas
    • San Antonio, Texas, United States, 78229
      • University Of Texas Medical School - San Antonio
    • Tyler, Texas, United States, 75701
      • Tyler Cardiovascular Consultants
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: A1	Drug: Apixaban; Tablets, Oral, 2.5 mg, twice daily, 26 weeks; Drug: Apixaban; Tablets, Oral, 10 mg, once daily, 26 weeks; Drug: Apixaban; Tablets, Oral 10 mg, twice daily, 26 weeks
EXPERIMENTAL: A2	Drug: Apixaban; Tablets, Oral, 2.5 mg, twice daily, 26 weeks; Drug: Apixaban; Tablets, Oral, 10 mg, once daily, 26 weeks; Drug: Apixaban; Tablets, Oral 10 mg, twice daily, 26 weeks
PLACEBO_COMPARATOR: A3	Drug: Placebo; Tablets, Oral, 0, twice daily, 26 weeks
EXPERIMENTAL: A4	Drug: Apixaban; Tablets, Oral, 2.5 mg, twice daily, 26 weeks; Drug: Apixaban; Tablets, Oral, 10 mg, once daily, 26 weeks; Drug: Apixaban; Tablets, Oral 10 mg, twice daily, 26 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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
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)
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• APPRAISE Steering Committee and Investigators; Alexander JH, Becker RC, Bhatt DL, Cools F, Crea F, Dellborg M, Fox KA, Goodman SG, Harrington RA, Huber K, Husted S, Lewis BS, Lopez-Sendon J, Mohan P, Montalescot G, Ruda M, Ruzyllo W, Verheugt F, Wallentin L. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the Apixaban for Prevention of Acute Ischemic and Safety Events (APPRAISE) trial. Circulation. 2009 Jun 9;119(22):2877-85. doi: 10.1161/CIRCULATIONAHA.108.832139. Epub 2009 May 26.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (ACTUAL): May 1, 2008
• Study Completion (ACTUAL): May 1, 2008

Study Registration Dates

• First Submitted: April 10, 2006
• First Submitted That Met QC Criteria: April 11, 2006
• First Posted (ESTIMATE): April 12, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): December 30, 2015
• Last Update Submitted That Met QC Criteria: November 25, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Apixaban
• Other Study ID Numbers: CV185-023