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Warfarin and Antiplatelet Vascular Evaluation

Primary Purpose

Peripheral Vascular Diseases, Cardiovascular Diseases

Status
Unknown status
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Warfarin
Sponsored by
Anand, Sonia, M.D.
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Peripheral Vascular Diseases focused on measuring Warfarin and Antiplatelet Vascular Evaluation, Peripheral vascular disease, Atherosclerosis, cardiovascular events, Ischemia, oral anticoagulants, low ankle-brachial index, moderate intensity warfarin, International normalized ratio [INR]

Eligibility Criteria

35 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Intermittent claudication with objective evidence of PVD (e.g. ankle-brachial index [ABI] < 0.90) Ischemic rest pain of the lower limbs Ischemic non-healing ulcers or focal gangrene Amputation for vascular causes Previous peripheral vascular revascularization (angioplasty or bypass surgery) Blue toe syndrome Other significant peripheral arterial disease (e.g. carotid stenosis) Vascular disease and evidence of asymptomatic peripheral arterial disease [PAD] (i.e. ABI < 0.90) Exclusion Criteria: Temporary: Potential subjects will be temporarily excluded if they need to undergo: vascular diagnostic (angiography) or interventional procedures (arterial bypass graft surgery or angioplasty); or limb amputation for vascular insufficiency. Permanent: Subjects will be excluded for the following: active bleeding or high risk bleeding; clear indication for long-term warfarin use (i.e. atrial fibrillation); previous allergy or intolerance to warfarin; stroke in the last 6 months; renal failure requiring dialysis; known significant abdominal aortic or cerebral aneurysm; peripheral arterial aneurysms (iliac or femoral) without evidence of lower limb ischemia; significant liver disease (i.e. cirrhosis); cancer with a life expectancy < 6 months; anticipated non-adherence to warfarin; excessive alcohol use; pregnancy or planning to become pregnant; or failure to provide informed consent.

Sites / Locations

  • Population Health Research Institute, McMaster University

Outcomes

Primary Outcome Measures

The composite of cardiovascular (CV) death, first occurrence of myocardial infarction (MI), or stroke
The composite of CV death, first occurrence of MI, stroke, or severe ischemia requiring urgent intervention of the coronary (PTCA, CABG) or peripheral artery circulation (thrombolytic therapy, angioplasty, bypass surgery, limb amputation)

Secondary Outcome Measures

CV death, MI, stroke, amputation, revascularization of the coronary or peripheral arteries, or admission to hospital for unstable angina with electrocardiogram (ECG) changes
CV death, MI, stroke, transient ischemic attack (TIA), amputation or revascularization of the coronary, carotid, or leg arteries
All cause death, MI, TIA, stroke, amputation, or revascularization of the coronary or peripheral arteries

Full Information

First Posted
July 29, 2005
Last Updated
September 27, 2009
Sponsor
Anand, Sonia, M.D.
Collaborators
Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario
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1. Study Identification

Unique Protocol Identification Number
NCT00125671
Brief Title
Warfarin and Antiplatelet Vascular Evaluation
Official Title
A Phase III Randomized Trial of Warfarin Plus Antiplatelet Therapy Versus Antiplatelet Therapy Alone in Patients With Peripheral Vascular Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Unknown status
Study Start Date
January 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
April 2006 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Anand, Sonia, M.D.
Collaborators
Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario

4. Oversight

5. Study Description

Brief Summary
The purpose of this study is to evaluate whether the addition of warfarin (a blood-thinning medication) to an antiplatelet therapy like aspirin is better than antiplatelet therapy alone (i.e. usual treatment) for the prevention of leg surgery, heart attacks, stroke and death in people with peripheral vascular disease.
Detailed Description
Atherosclerosis is the underlying cause of peripheral vascular disease (PVD) of the lower extremities, and leads to intermittent claudication, leg ulceration and gangrene. More importantly, symptomatic PVD is an ominous sign that widespread atherosclerosis is present and patients with this condition suffer a threefold increase in myocardial infarction (MI), stroke, and CV death. These CV events are a consequence of rupture of an atherosclerotic plaque, which leads to platelet activation and thrombin generation, thrombus formation and occlusion of a critical blood vessel. Antiplatelet therapy has been clearly demonstrated to reduce major CV events. It is also reasonable to expect that this process may be further attenuated by the addition of an anti-thrombin agent (such as warfarin) in combination with antiplatelet agents. WAVE is a large, international, multicentre, randomized clinical trial in high-risk PVD patients to evaluate the additional benefit of moderate intensity warfarin (target INR of 2.4-3.0) to antiplatelet therapy compared to antiplatelet therapy alone in reducing serious cardiovascular events. There are currently 80 active centres following participants in Canada, Poland, Australia, Hungary, China, Ukraine, and the Netherlands. Following randomization to one of the two treatment groups, participants will require clinic or phone follow-up visits every 3 months for 2.5 or 3.5 years. For participants on warfarin, INRs will be measured monthly or more frequently if required. For participants who stop warfarin therapy prematurely, every attempt will be made to have them restart it

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral Vascular Diseases, Cardiovascular Diseases
Keywords
Warfarin and Antiplatelet Vascular Evaluation, Peripheral vascular disease, Atherosclerosis, cardiovascular events, Ischemia, oral anticoagulants, low ankle-brachial index, moderate intensity warfarin, International normalized ratio [INR]

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2400 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Warfarin
Primary Outcome Measure Information:
Title
The composite of cardiovascular (CV) death, first occurrence of myocardial infarction (MI), or stroke
Title
The composite of CV death, first occurrence of MI, stroke, or severe ischemia requiring urgent intervention of the coronary (PTCA, CABG) or peripheral artery circulation (thrombolytic therapy, angioplasty, bypass surgery, limb amputation)
Secondary Outcome Measure Information:
Title
CV death, MI, stroke, amputation, revascularization of the coronary or peripheral arteries, or admission to hospital for unstable angina with electrocardiogram (ECG) changes
Title
CV death, MI, stroke, transient ischemic attack (TIA), amputation or revascularization of the coronary, carotid, or leg arteries
Title
All cause death, MI, TIA, stroke, amputation, or revascularization of the coronary or peripheral arteries

10. Eligibility

Sex
All
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Intermittent claudication with objective evidence of PVD (e.g. ankle-brachial index [ABI] < 0.90) Ischemic rest pain of the lower limbs Ischemic non-healing ulcers or focal gangrene Amputation for vascular causes Previous peripheral vascular revascularization (angioplasty or bypass surgery) Blue toe syndrome Other significant peripheral arterial disease (e.g. carotid stenosis) Vascular disease and evidence of asymptomatic peripheral arterial disease [PAD] (i.e. ABI < 0.90) Exclusion Criteria: Temporary: Potential subjects will be temporarily excluded if they need to undergo: vascular diagnostic (angiography) or interventional procedures (arterial bypass graft surgery or angioplasty); or limb amputation for vascular insufficiency. Permanent: Subjects will be excluded for the following: active bleeding or high risk bleeding; clear indication for long-term warfarin use (i.e. atrial fibrillation); previous allergy or intolerance to warfarin; stroke in the last 6 months; renal failure requiring dialysis; known significant abdominal aortic or cerebral aneurysm; peripheral arterial aneurysms (iliac or femoral) without evidence of lower limb ischemia; significant liver disease (i.e. cirrhosis); cancer with a life expectancy < 6 months; anticipated non-adherence to warfarin; excessive alcohol use; pregnancy or planning to become pregnant; or failure to provide informed consent.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sonia Anand, MD PhD FRCPc
Organizational Affiliation
Population Health Research Institute, McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Population Health Research Institute, McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8L 2X2
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
16368284
Citation
WAVE Investigators. The effects of oral anticoagulants in patients with peripheral arterial disease: rationale, design, and baseline characteristics of the Warfarin and Antiplatelet Vascular Evaluation (WAVE) trial, including a meta-analysis of trials. Am Heart J. 2006 Jan;151(1):1-9. doi: 10.1016/j.ahj.2005.03.021.
Results Reference
background
PubMed Identifier
17634457
Citation
Warfarin Antiplatelet Vascular Evaluation Trial Investigators; Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj A, Sussex B, Liu L, Guzman R, Cina C, Crowell R, Keltai M, Gosselin G. Oral anticoagulant and antiplatelet therapy and peripheral arterial disease. N Engl J Med. 2007 Jul 19;357(3):217-27. doi: 10.1056/NEJMoa065959.
Results Reference
derived

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Warfarin and Antiplatelet Vascular Evaluation

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