A Phase III Study of Apixaban in Patients With Atrial Fibrillation
- Registration Number
- NCT00496769
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this clinical research study is to determine whether apixaban is more effective than acetylsalicylic acid in the prevention of strokes associated with patients with atrial fibrillation. The safety of this treatment will also be studied.
- Detailed Description
An optional Long-term Open-label Extension Phase of treatment with apixaban will be provided for qualifying participants following the conclusion of the double-blind phase
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 6421
-
Male and female
-
Age of 50 years or older
-
Permanent, paroxysmal, or persistent atrial fibrillation (at screening or within 6 months prior to enrollment) documented by 12-lead electrocardiogram)
-
At least 1 of the following risk factors for stroke:
- Prior stroke or transient ischemic attack
- Age of 75 years or older
- Arterial hypertension on treatment
- Diabetes mellitus
- Heart failure (New York Health Authority Class 2 or greater at time of enrollment)
- Left ventricular ejection fraction of 35% or less, documented within 6 months of enrollment
- Peripheral arterial disease (previous arterial revascularization, limb or foot amputation, or current intermittent claudication with ankle-arm systolic blood pressure ratio <0.9)
-
Not currently receiving vitamin K antagonist therapy for 1 of the following reasons:
- Previous vitamin K antagonist therapy demonstrated as unsuitable and discontinued
- Vitamin K antagonist therapy not previously used but expected unsuitable
Key
-
Women who are pregnant or breast feeding
-
Women of child bearing potential who are unwilling to meet the study requirements for pregnancy testing or are unwilling or unable to use an acceptable method to avoid pregnancy
-
Atrial fibrillation due to reversible causes, such as thyrotoxicosis or pericarditis
-
Valvular disease requiring surgery
-
Planned ablation procedure for atrial fibrillation to be performed within 3 months
-
Conditions other than atrial fibrillation that require chronic anticoagulation (such as, prosthetic mechanical heart valve, venous thromboembolism)
-
Patients with serious bleeding in the last 6 months or at high risk for bleeding, including but not limited to those with:
- Active peptic ulcer disease
- Platelet count <100,000/mm^3 or hemoglobin <10g/dL
- Recent stroke (within 10 days)
- Documented hemorrhagic tendencies or blood dyscrasias
-
Current alcohol or drug abuse or psychosocial reasons that make study participation impractical
-
Severe comorbid condition with life expectancy <1 year
-
Severe renal insufficiency; any patient with a serum creatinine level >2.5 mg/dL or a calculated creatinine clearance <25 mL/min is excluded
-
Alanine transaminase or aspartate aminotransferase levels >2 times upper limit of normal (ULN) or a total bilirubin level >1.5 times ULN (unless an alternative causative factor [such as Gilbert's syndrome] is identified)
-
Allergy or adverse reaction to acetylsalicylic acid
-
Required treatment with a thienopyridine (clopidogrel or ticlopidine)
-
Prisoners or participants who are compulsory detained (involuntarily incarcerated)
-
Use of an investigational drug or device within the past 30 days or prior randomization into an apixaban clinical study
-
Patients who are compulsorily detained for treatment for a psychiatric or physical illness
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Apixaban Apixaban - Acetylasalicylic acid Acetylsalicylic acid -
- Primary Outcome Measures
Name Time Method Event Rate of Stroke/Systemic Embolism During the Intended-treatment Period Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) Event rate=percent of participants with an event divided by the total participants in the arm. Intended-treatment period=date of randomization to the efficacy cutoff date, which was to be the date on which at least 226 unrefuted original primary efficacy events occurred (date revised to May 28, 2010 following cessation of study for superior efficacy.)
- Secondary Outcome Measures
Name Time Method Event Rates for Major Bleeding, Major or Clinically Relevant Nonmajor (CNRM) Bleeding, and All Bleeding in the Double-blind Period First dose of study drug (Day 1) to the earlier of a patient's discontinuation of double-blind study drug or the attainment of at least 226 primary efficacy events up to May 28, 2010 Event rate=percent of participants with an event divided by the total participants in the arm.
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality First dose of study drug (Day 1) to 30 days after last dose of blinded study drug BL=baseline, LLN=lower limit of normal, ULN=upper limit of normal. Hemoglobin (g/dL), low: BL\>2 or value ≤8; hematocrit(%), low: \<0.75\*BL; erythrocytes (\*10\^6 cells/μL), low: \<0.75\*BL; platelet count (\*10\^9 cells/L),low: \<100\*10\^9 cells/L; leukocytes (\*10\^3 cells/μL), low if \<0.8\*BL and BL\<LLN or \<LLN and BL \>ULN or \<0.75\*LLN when BL is missing or LLN ≤BL≤ ULN, high if \>1.2\*BL and BL\>ULN or \>ULN when BL and BL\<LLN or \>1.25\*ULN when BL is missing or LLN≤BL≤ULN; neutrophils (absolute), low: \<1.0\*10\^3 cells/μL; eosinophils (absolute), high: \>0.750\*10\^3 cells/μL; basophils (absolute), high: \>0.4\*10\^3 cells/μL; monocytes (absolute), high: 2\*10\^3 cells/μL; lymphocytes (absolute), low if \<0.75\*10\^3 cells/μL, high if \>7.50\*10\^3 cells/μL; ALP (U/L), high: 2\*ULN; AST (U/L), high: 3\*ULN; AST (U/L), high: 3\*ULN; bilirubin, total (mg/dL), high: \>2\*ULN; bilirubin, direct (mg/dL), high: 1.5\*ULN; BUN (mg/dL), high:\>2\*ULN; creatinine (mg/dL), high: \>1.5\*ULN.
Event Rate for the Composite of Stroke of Any Type, Systemic Embolism, Myocardial Infarction, or Vascular Death During the Double-blind Treatment Period Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) Event rate=percent of participants with an event divided by the total participants in the arm.
Event Rate of All-cause Death; Net Clinical Benefit-Composite of Stroke, Systemic Embolism, Myocardial Infarction, Vascular Death, and Major Bleeding; and Vascular Death Randomization to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) Event rate=percent of participants with an event divided by the total participants in the arm.
Rate of Unrefuted Bleeding From First Dose of Double-blind Study Drug to First Occurence of Unrefuted Bleeding During the Double-blind Treatment Period Day 1 to first bleeding event up to efficacy cutoff date of May 28, 2010 (date revised following cessation of study for superior efficacy) Event rate=percent of participants with an event divided by the total participants in the arm.
Number of Participants With Serious Adverse Events (SAEs), Adverse Events (AEs), Bleeding AEs, Discontinuations Due to AEs, and Death as Outcome First dose of study drug (Day 1) to 30 days after last dose of blinded study drug AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Abnormality (Continued) First dose of study drug (Day 1) to 30 days after last dose of blinded study drug ULN=upper limit of normal; LLN=lower limit of normal; BL=baseline. Creatine kinase (U/L), high:\>5\*ULN; protein, total(g/L):low if \<0.90\*BL when BL\<LLN or \<LLN when B \>ULN or \<0.90\*LLN when BL is missing or LLN≤BL≤ULN, high if \>1.10\*BL if BL\>ULN or \>ULN when BL\<LLN or \>1.10\*ULN if BL missing or LLN≤BL≤ULN.Protein,total(g/L): low if \<0.90\*BL if BL\<LLN or \<LLN if BL\>ULN or \<0.90\*LLN if BL missing or LLN≤BL≤ULN, high if \>1.10\*BL if BL\>ULN or \>ULN if BL\<LLN or \>1.10\*ULN if BL or LLN≤BL≤ULN; glucose, serum fasting (mg/dL): low if \<0.8\*BL if BL\<LLN or \<LLN when BL\>ULN or \<0.8\*LLN when BL missing or LLN≤BL≤ULN, high if \>2\*BL when BL\>ULN or \>ULN when BL\<LLN or \>1.5\*ULN if BL missing or LLN≤BL≤ULN; uric acid (mg/dL), high: \>2\*BL and BL\>ULN or\>1.5\*ULN when BL missing or BL≤ULN; glucose, urine, high; protein, urine, high; blood, urine, high; leukocyte esterase, urine, high; RBC count, urine (Hpf), high; WBC count, urine (Hpf), high: ≥2 if BL=missing,=0 or =0.5 or if ≥3 if BL=1, or if ≥4 and BL≥2.
Trial Locations
- Locations (68)
Stamford Therapeutics Consortium
🇺🇸Stamford, Connecticut, United States
Kaiser Permanente Medical Center, West Los Angeles
🇺🇸Los Angeles, California, United States
Southwest Heart
🇺🇸Tucson, Arizona, United States
Yogesh K. Paliwal Md
🇺🇸Pomona, California, United States
Bay Pines Va Healthcare System
🇺🇸Bay Pines, Florida, United States
Desert Med Grp Inc, Dba Desert Oasis Healthcare Med Group
🇺🇸Palm Springs, California, United States
Mobile Heart Specialists, Pc
🇺🇸Mobile, Alabama, United States
Michigan Heart And Vascular Specialists
🇺🇸Petoskey, Michigan, United States
Ira R. Friedlander, M.D.
🇺🇸Canton, Ohio, United States
St. Vincent'S Ambulatory Care, Inc
🇺🇸Jacksonville, Florida, United States
Dr William Kufs
🇺🇸Saratoga Springs, New York, United States
Terry V. Arnold, Md
🇺🇸Lexington, North Carolina, United States
Grand View - Lehigh Valley Health Services
🇺🇸Sellersville, Pennsylvania, United States
Cardiology Consultants Of Orange County Med. Group Inc
🇺🇸Anaheim, California, United States
The Broward Heart Group, Pa
🇺🇸Tamarac, Florida, United States
Great Lakes Heart Center Of Alpena
🇺🇸Alpena, Michigan, United States
Hillsboro Cardiology Pc
🇺🇸Hillsboro, Oregon, United States
Missouri Cardiovascular Specialists
🇺🇸Columbia, Missouri, United States
Capital Cardiology Associates
🇺🇸Troy, New York, United States
Baptist Heart Specialists
🇺🇸Jacksonville Beach, Florida, United States
Southeast Regional Research Group
🇺🇸Savannah, Georgia, United States
Santa Rosa Cardiology
🇺🇸Santa Rosa, California, United States
The Heart & Vascular Institute Of Florida
🇺🇸Clearwater, Florida, United States
Kim A. Klancke, Md
🇺🇸Daytona Beach, Florida, United States
Michael F. Lesser, Md, Facc Osler Medical Inc.
🇺🇸Melbourne, Florida, United States
North County Internal Medicine
🇺🇸Vista, California, United States
Academic Cardiology Associates
🇺🇸Rochester Hills, Michigan, United States
Long Island Heart Associates
🇺🇸Mineola, New York, United States
Oregon Medical Group - Clinical Research
🇺🇸Eugene, Oregon, United States
Internal Medicine Of Greer
🇺🇸Greer, South Carolina, United States
Lowcountry Medical Group, Llc
🇺🇸Beaufort, South Carolina, United States
Davis Heart & Lung Research Institute
🇺🇸Columbus, Ohio, United States
Hunterdon Cardiovascular Associates
🇺🇸Flemington, New Jersey, United States
West Chester Cardiology
🇺🇸West Chester, Pennsylvania, United States
Pinehurst Medical Clinic, Inc
🇺🇸Pinehurst, North Carolina, United States
Knoxville Heart Group
🇺🇸Knoxville, Tennessee, United States
Comprehensive Cardiology Consultants
🇺🇸Langhorne, Pennsylvania, United States
Marshfield Clinic
🇺🇸Marshfield, Wisconsin, United States
Local Institution
🇬🇧Chichester, West Sussex, United Kingdom
Indiana Heart Physicians, Inc.
🇺🇸Indianapolis, Indiana, United States
The Care Group, Llc
🇺🇸Indianapolis, Indiana, United States
University Of California, San Diego
🇺🇸San Diego, California, United States
Integris Cardiovascular Physicians
🇺🇸Oklahoma City, Oklahoma, United States
South Oklahoma Heart Research
🇺🇸Oklahoma City, Oklahoma, United States
The Portland Clinic, Llp
🇺🇸Portland, Oregon, United States
San Diego Managed Care Group
🇺🇸Poway, California, United States
Cardiology Associates Of New Haven,Pc
🇺🇸Guilford, Connecticut, United States
Research Alliance, Inc.
🇺🇸Clearwater, Florida, United States
The Heart Group Pl
🇺🇸Fort Myers, Florida, United States
Cardiovascular Center Of Sarasota
🇺🇸Sarasota, Florida, United States
Fox Valley Clinical Research Center, Llc
🇺🇸Aurora, Illinois, United States
North Chicago Va Medical Center
🇺🇸North Chicago, Illinois, United States
Hutchinson Clinic, Pa
🇺🇸Hutchinson, Kansas, United States
Peninsula Cardiology Associates, P.A.
🇺🇸Salisbury, Maryland, United States
Dr. Jeffrey Chen
🇺🇸Lafayette, Louisiana, United States
Tupelo Neurology Clinic, Pa
🇺🇸Tupelo, Mississippi, United States
Glacier View Cardiology, Pc
🇺🇸Kalispell, Montana, United States
Nyu Hudson Valley Cardiology
🇺🇸Cortlandt Manor, New York, United States
Medical University Of South Carolina
🇺🇸Charleston, South Carolina, United States
Cardiology Consultants Of Philadelphia
🇺🇸Yardley, Pennsylvania, United States
Sentara York Clinical Research
🇺🇸Norfolk, Virginia, United States
Roanoke Heart Institute, Plc
🇺🇸Roanoke, Virginia, United States
Walla Walla Clinic
🇺🇸Walla Walla, Washington, United States
Henry Ford Hospital K-15
🇺🇸Detroit, Michigan, United States
Salem Veterans Administration Medical Center
🇺🇸Salem, Virginia, United States
Sanford Cardiology
🇺🇸Sanford, North Carolina, United States
University Of Missouri
🇺🇸Columbia, Missouri, United States
Pentucket Medical Associates
🇺🇸Haverhill, Massachusetts, United States