Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

Stroke Clinical Trial

— WARCEF  

Official title:

Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00041938
• Other study ID #: AAAC1093
• Secondary ID: U01NS039143-01R0
• Status: Completed
• Phase: Phase 3
• First received: July 19, 2002
• Last updated: August 29, 2014
• Start date: October 2002
• Est. completion date: July 2014

Study information

• Verified date: August 2014
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine which of two treatments, Warfarin or aspirin, is better for preventing death and stroke in patients with poor heart function.

We are now transitioning into the sub-analysis part of the WARCEF patient data.

The study has recently completed data analysis for its Primary Aim. All randomized patients have completed their follow up. All study related procedure as per the protocol has been completed. We are now in the extension phase of the study to obtain more patient data to address further aims of the study. No new procedures are performed and data already in place at the sites will be collected (EKG and echocardiograms).

The aims for this study extension are:

• To assess progression of cardiac dysfunction over time among heart failure patients

• To correlate prognosis with cardiac dysfunction

Description:

Warfarin has proven effective in patients with ischemic heart disease, especially in the reduction of stroke, death and re-infarction following myocardial infarction, and in the reduction of stroke in atrial fibrillation. Warfarin is the most promising unstudied intervention in patients with cardiac failure. This randomized, double-blind, multi-center study will define optimal antithrombotic therapy for patients with cardiac (heart) failure and patients with low ejection fraction (EF). EF is the proportion of left ventricular volume emptied during systole. It reliably measures left ventricular systolic function.

With the rapidly increasing numbers of elderly patients with heart failure, this study has important public health implications. The study will determine which of two commonly used treatments Warfarin, an anticoagulant, or aspirin, a drug which affects platelet function is better for preventing death and stroke in patients with low ejection fraction.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2305
• Est. completion date: July 2014
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Cardiac EF <=35% by radionuclide ventriculography, left ventriculography or quantitive echocardiographic measurement or an echocardiographic Wall Motion Index of <=1.2, within three months of enrollment. The patient's clinical cardiac state at enrollment should be similar to their state at the time of the qualifying echocardiogram. The qualifying left ventricular function measurement must be obtained at least three months after an MI, coronary bypass grafting, PTCA, and at least one month after pacemaker insertion. Patients scheduled for mitral valve repair should have qualifying echo after surgery.

• Modified Rankin score <=4.

• Patient must be taking ACE inhibitors. If intolerant of ACE inhibitor, patient must be on angiotensin II receptor blockers or hydralazine and nitrates.

• Patient is able to follow an outpatient protocol (requiring monthly blood tests and clinic visits every four months for the duration of the study) and is available by telephone.

• Patient understands the purpose and requirements of the study, can make him/herself understood, and has provided informed consent.

• Patients with recent stroke or TIA within twelve (12) months will be eligible to be included in the recent stroke (RS) subgroup.

• Chronic CHF patients (NYHA I * IV) admitted to the hospital can be randomized prior to discharge if the patient is stable, taking oral medications for 24 hours and ambulatory at the time of discharge. Stable New York Heart Association Class IV patients will be eligible for randomization.

Exclusion Criteria

• The presence of any of the following unequivocal cardiac sources of embolism: chronic or paroxysmal AF, mechanical valve, endocarditis, intracardiac mobile or pedunculated thrombus, and valvular vegetation.

• Cyanotic congenital heart disease, Eisenmenger's syndrome.

• Decompensated heart failure.

• Cardiac surgery, angioplasty, or MI within the past 3 months prior to randomization.

• A contraindication to the use of either warfarin or aspirin, e.g. active peptic ulcer disease, active bleeding diathesis, platelets <100,000*, hematocrit <30, INR >1.3 (if not on warfarin), clotting factor abnormality that increases the risk of bleeding, alcohol or substance abuse, severe gait instability, cerebral hemorrhage, systemic hemorrhage within the past year, severe liver impairment (AST >3x normal*, cirrhosis), any condition requiring regular use of non-steroidal anti-inflammatory agents, allergy to aspirin or warfarin, uncontrolled severe hypertension (systolic pressure >180 mm Hg or diastolic pressure > 110 mm Hg), positive stool guaiac not attributable to hemorrhoids, creatinine >3.0*. *on most recent test done within 30 days prior to randomization

• Patient needs continuing therapy with intravenous heparin or low molecular weight heparin or a specific antiplatelet agent.

• Dementia or psychiatric or physical problem that prevents the patient from following an outpatient program reliably.

• Comorbid conditions that may limit survival to less than five years.

• Pregnancy, or female of childbearing potential who is not sterilized or is not using a medically accepted form of contraception* (see procedure manual). *A pregnancy test is required for all women of childbearing age.

• Enrollment in another study that would conflict with WARCEF.

• Hospitalization for new diagnosis of onset CHF within the past one month or carotid endarterectomy or pacemaker insertion within the past one month prior to randomization .

• Person under 18 years of age.

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Heart Disease
• Heart Diseases
• Infarction
• Ischemic Heart Disease
• Myocardial Infarction
• Myocardial Ischemia
• Stroke

Intervention

Drug:
• aspirin
325 mg per day
• Warfarin
INR 2.5-3.0; target INR 2.75

Locations

Country	Name	City	State
Canada	QE II Health Sciences Centre	Halifax	Nova Scotia
Canada	Center for Neurologic Research	Lethbridge	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Montreal Heart Institute	Montreal	Quebec
Canada	Ottawa Heart Institute	Ottawa	Ontario
Canada	Etobicoke Cardiac Research Centre	Rexdale	Ontario
Canada	Saint John Regional Hospital	Saint John	New Brunswick
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	St. Boniface General Hospital	Winnipeg	Manitoba
United States	Albany Medical College	Albany	New York
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Morehouse School of Medicine	Atlanta	Georgia
United States	Tri-State Medical Group Cardiology	Beaver	Pennsylvania
United States	Buffalo General Hospital	Buffalo	New York
United States	Kaleida Health Millard Fillmore Hospital	Buffalo	New York
United States	Lahey Clinic	Burlington	Massachusetts
United States	Five Towns Neuroscience Research	Cedarhurst	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Illinois at Chicago	Chicago	Illinois
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Concord Hospital	Concord	New Hampshire
United States	Denver Health Medical Center	Denver	Colorado
United States	Denver Veterans Affairs Medical Center	Denver	Colorado
United States	Veterans Affairs Medical Center	Detroit	Michigan
United States	Black Hills Health Care System	Fort Meade	South Dakota
United States	Brooke Army Medical Center MCHE - MDC Cardiology Service	Ft. Sam Houston	Texas
United States	Northeast Georgia Heart Center	Gainesville	Georgia
United States	Michael E. DeBakey Veterans Affairs Medical Center-MEDVAMC	Houston	Texas
United States	Huntington Veterans Affairs Medical Center	Huntington	West Virginia
United States	Mayo Clinic Transplant Center	Jacksonville	Florida
United States	Sewickley Valley Medical Group, Cardiology	Leetsdale	Pennsylvania
United States	University of Kentucky	Lexington	Kentucky
United States	Louisville Veterans Affairs Medical Center	Louisville	Kentucky
United States	University of Louisville	Louisville	Kentucky
United States	William S. Middleton Memorial Veterans Hospital	Madison	Wisconsin
United States	Melbourne Internal Medicine Associates	Melbourne	Florida
United States	Gulf Regional Research, LLC	Metairie	Louisiana
United States	Jackson Memorial Hospital/U. of Miami	Miami	Florida
United States	Mercy Research Institute	Miami	Florida
United States	Mercy Health Partners	Muskegon	Michigan
United States	UMDNJ - New Brunswick	New Brunswick	New Jersey
United States	Long Island Jewish Medical Center	New Hyde Park	New York
United States	Columbia University Medical Center	New York	New York
United States	Columbia University, New York Presbyterian Hospital PH 3-342	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	University of Medicine and Dentistry of New Jersey	Newark	New Jersey
United States	Northport Veterans Affairs Medical Center	Northport	New York
United States	Oklahoma City Veterans Affairs Medical Center	Oklahoma City	Oklahoma
United States	Methodist Heart, Lung and Vascular Institute	Peoria	Illinois
United States	Albert Einstein Medical Center	Philadelphia	Pennsylvania
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Reno Veterans Affairs Medical Center	Reno	Nevada
United States	University of Rochester Medical Center	Rochester	New York
United States	Salem VAMC	Salem	Virginia
United States	Santa Clara Medical Center	Santa Clara	California
United States	LSU Health Sciences Center	Shreveport	Louisiana
United States	Cardiovascular Consultants of South Florida	Tamarac	Florida
United States	Southern Arizona Veterans Affairs Medical Center	Tucson	Arizona
United States	University of Arizona Health Sciences Center	Tucson	Arizona
United States	George Washington University	Washington	District of Columbia
United States	West Los Angeles Veterans Affairs Medical Center	West Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Columbia University	National Institute of Neurological Disorders and Stroke (NINDS)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Event Rate Per 100 Patient-years for Ischemic Stroke	Time, in years, from date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient-years for Intracerebral Hemorrhage	Time, in years, from date of randomization to date of intracerebral hemorrhage component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient-years for Death	Time, in years, from date of randomization to date of death component of primary composite outcome. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of death component of primary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome	Time, in years, from date of randomization to date of myocardial infarction, up to 6 years. Includes only myocardial infarctions that occurred during follow-up, before any heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with myocardial infarction)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome.	Time, in years, from date of randomization to date of heart failure hospitalization, up to 6 years. Includes hospitalizations for heart failure during follow-up that were not preceded by myocardial infarction. Event rate per 100 patient years = 100*(number of subjects with heart failure hospitalization)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome	Ischemic stroke component of secondary composite endpoint. Includes only ischemic strokes that were not preceded by a myocardial infarction or heart failure hospitalization. The number of ischemic strokes that are components of the secondary outcome does not therefore match the number of ischemic strokes that are components of the primary outcome. Event rate per 100 patient years = 100*(number of subjects with ischemic stroke)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.	From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome	Time, in years, from date of randomization to date of intracerebral hemorrhage component of secondary composite outcome. Includes only intracerebral hemorrhages not preceded by myocardial infarction or heart failure hospitalization. Event rate per 100 patient years = 100*(number of subjects with intracerebral hemorrhage)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years	Yes
Other	Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome	Time, in years, from randomization to death component of secondary composite outcome. This measure counts only deaths that were not preceded by heart failure hospitalization, myocardial infarction, ischemic stroke, or intracerebral hemorrhage. Event rate per 100 patient years = 100*(number of subjects who died)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization to date of death component of secondary composite outcome, up to 6 years	Yes
Other	Rate Per 100 Patient Years of Major Hemorrhage	Rate/100 patient-years of major hemorrhage. Includes all major hemorrhages in any patient. Major hemorrhage was defined as intracerebral, epidural, subdural, subarachnoid, spinal intramedullary, or retinal hemorrhage; any other bleeding causing a decline in the hemoglobin level of more than 2 g per deciliter in 48 hours; or bleeding requiring transfusion of 2 or more units of whole blood, hospitalization, or surgical intervention. Event rate per 100 patient years = 100*(number of major hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization until end of scheduled follow-up, up to 6 years	Yes
Other	Rate Per 100 Patient-years of Minor Hemorrhage.	Rate per 100 patient years of minor hemorrhage. Includes all minor hemorrhages. Minor hemorrhage was defined as any non-major hemorrhage. Event rate per 100 patient years = 100*(number of minor hemorrhage events)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1)of all randomized patients / 365.25.	From date of randomization until the end of scheduled follow-up, up to 6 years	Yes
Primary	Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death	The time, in years, from randomization to the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years. Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years	Yes
Secondary	Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death.	The time, in years, from date of randomization to the date of the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to 6 years.; Event rate per 100 patient years = 100*(number of subjects with event)/patient-years of follow-up. Patient years of follow-up = sum(date of conclusion of follow-up - date of randomization + 1) of all randomized patients / 365.25.	From randomization to the first to occur of hospitalization for heart failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, or death, up to a maximum of 6 years.	Yes