Trial record 1 of 1 for:    WARCEF
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Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Shunichi Homma, Columbia University
ClinicalTrials.gov Identifier:
NCT00041938
First received: July 19, 2002
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

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

Condition Intervention Phase
Heart Disease
Stroke
Ischemic Heart Disease
Myocardial Infarction
Drug: aspirin
Drug: Warfarin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Warfarin Versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) Trial

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Event Rate Per 100 Patient Years for Composite Endpoint of Ischemic Stroke, Intracerebral Hemorrhage, or Death [ Time Frame: From date of randomization until the date of the first to occur of ischemic stroke, intracerebral hemorrhage, or death, up to 6 years ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Event Rate Per 100 Patient-years for Composite Endpoint of Hospitalization for Heart Failure, Myocardial Infarction, Ischemic Stroke, Intracerebral Hemorrhage, or Death. [ Time Frame: 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. ] [ Designated as safety issue: Yes ]

    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.



Other Outcome Measures:
  • Event Rate Per 100 Patient-years for Ischemic Stroke [ Time Frame: From date of randomization to date of ischemic stroke component of primary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient-years for Intracerebral Hemorrhage [ Time Frame: From date of randomization to date of intracerebral hemorrhage component of primary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient-years for Death [ Time Frame: From date of randomization to date of death component of primary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient Years of Myocardial Infarction Component of Secondary Composite Outcome [ Time Frame: From date of randomization to date of myocardial infarction component of secondary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient Years of Heart Failure Hospitalization Component of Secondary Composite Outcome. [ Time Frame: From date of randomization to date of heart failure hospitalization component of secondary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient Years of Ischemic Stroke Component of Secondary Composite Outcome [ Time Frame: From date of randomization to date of ischemic stroke component of secondary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient Years of Intracerebral Hemorrhage Component of Secondary Composite Outcome [ Time Frame: From date of randomization to date of intracerebral hemorrhage component of secondary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Event Rate Per 100 Patient Years of Death Component of Secondary Composite Outcome [ Time Frame: From date of randomization to date of death component of secondary composite outcome, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Rate Per 100 Patient Years of Major Hemorrhage [ Time Frame: From date of randomization until end of scheduled follow-up, up to 6 years ] [ Designated as safety issue: Yes ]
    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.

  • Rate Per 100 Patient-years of Minor Hemorrhage. [ Time Frame: From date of randomization until the end of scheduled follow-up, up to 6 years ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 2305
Study Start Date: October 2002
Study Completion Date: July 2014
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: aspirin
Aspirin: 325 mg per day
Drug: aspirin
325 mg per day
Active Comparator: warfarin
Warfarin: International Normalized Ratio (INR) 2.5-3.0; target INR 2.75
Drug: Warfarin
INR 2.5-3.0; target INR 2.75

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00041938

  Show 64 Study Locations
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Shunichi Homma, M.D. Principal Cardiologist, Associate Chief, Division of Cardiology, and Director, Echocardiography Laboratories Professor of Medicine
Principal Investigator: Seamus Thompson, PhD Statistical PI: Clinical Professor of Biostatistics and Neurology
  More Information

No publications provided by Columbia University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Shunichi Homma, Margaret Milliken Hatch Professor of Medicine at the New York-Presbyterian Hospital at the Columbia University Medical Center (In Biomedical Engineering), Columbia University
ClinicalTrials.gov Identifier: NCT00041938     History of Changes
Other Study ID Numbers: AAAC1093, U01NS039143-01, R01NS39154, CRC
Study First Received: July 19, 2002
Results First Received: January 3, 2013
Last Updated: August 29, 2014
Health Authority: United States: Federal Government

Keywords provided by Columbia University:
heart disease
stroke
ischemic heart disease
myocardial infarction
atrial fibrillation
low ejection fraction
cardiac failure
aspirin
Warfarin
anticoagulant

Additional relevant MeSH terms:
Infarction
Heart Diseases
Myocardial Infarction
Coronary Artery Disease
Myocardial Ischemia
Ischemia
Pathologic Processes
Necrosis
Cardiovascular Diseases
Vascular Diseases
Coronary Disease
Arteriosclerosis
Arterial Occlusive Diseases
Aspirin
Warfarin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents

ClinicalTrials.gov processed this record on September 16, 2014