Peripheral Vascular DiseasesPhase 3NCT00125671
Warfarin and Antiplatelet Vascular Evaluation
A Phase 3 study testing Warfarin in people with Peripheral Vascular Diseases and Cardiovascular Diseases, run by Anand, Sonia, M.D. at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 85 years
- Conditions the study is for
- Peripheral Vascular Diseases, Cardiovascular Diseases
- What is being tested?
- Warfarin
- How many people
- 2,400 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2000to Apr 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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:
Show all 19Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Population Health Research Institute, McMaster University
Hamilton, Ontario, L8L 2X2
About this study
Official title: A Phase III Randomized Trial of Warfarin Plus Antiplatelet Therapy Versus Antiplatelet Therapy Alone in Patients With Peripheral Vascular Disease
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.
Read the 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
- Being tested
- Warfarin
- 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]
- Medical subject headings
- Peripheral Vascular Diseases, Cardiovascular Diseases, Atherosclerosis, Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WarfarinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (3)
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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2005 (estimated)
- Study startJan 2000
- Study completionApr 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Peripheral Vascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2,400 participants
Sponsor and investigators
- Lead sponsor
- Anand, Sonia, M.D.
- Collaborators
- Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario
- Investigators
- Sonia Anand, MD PhD FRCPc, Principal investigator, Population Health Research Institute, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00125671
- Sponsor's protocol ID
- MCT-37413
- Other IDs
- T4913
- Status last verified
- Sep 2009
- First submitted
- 29 Jul 2005
- Last updated
- 29 Sep 2009
- Results posted
- No
Publications
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.
PubMed 16368284Warfarin 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.
PubMed 17634457
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III Randomized Trial of Warfarin Plus Antiplatelet Therapy Versus Antiplatelet Therapy Alone in Patients With Peripheral Vascular Disease
- ClinicalTrials.gov ID
- NCT00125671
- Acronym / sponsor ID
- MCT-37413
- Keywords
- Warfarin and Antiplatelet Vascular Evaluation, Peripheral vascular disease, Atherosclerosis, cardiovascular events, Ischemia, oral anticoagulants, low ankle-brachial index, moderate intensity warfarin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 2,400 participants
- Lead sponsor
- Anand, Sonia, M.D.
- Collaborators
- Canadian Institutes of Health Research (CIHR), Heart and Stroke Foundation of Ontario
- Study start
- Jan 2000
- Study completion
- Apr 2006
- First posted
- 1 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 35 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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)
Key exclusion criteria (19 listed)
- Potential subjects will be temporarily excluded if they need to undergo:
- Subjects will be excluded for the following:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Warfarin | Drug | – |
Primary outcome
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)
3 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2009.
- Background: PubMed 16368284WAVE 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.
- Derived from this study: PubMed 17634457Warfarin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sonia Anand, MD PhD FRCPc principal investigator
Population Health Research Institute, McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Warfarin in people with Peripheral Vascular Diseases and Cardiovascular Diseases, run by Anand, Sonia, M.D. at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Sep 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The composite of cardiovascular (CV) death, first occurrence of myocardial infarction (MI), or stroke. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00125671, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2009.