A Phase 2, Open Label, Pilot Study to Examine the Use of Rivaroxaban Plus Aspirin vs. Clopidogrel Plus Aspirin for the Prevention of Restenosis After Infrainguinal Percutaneous Transluminal Angioplasty for Critical Limb Ischemia
Overview
- Phase
- Phase 2
- Intervention
- clopidogrel plus aspirin
- Conditions
- Critical Limb Ischemia
- Sponsor
- Ottawa Hospital Research Institute
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Reintervention, Above Ankle Amputation and Restenosis (RAS)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
Background: Up to 10% of patients with peripheral arterial disease (PAD) will develop critical limb ischemia (CLI) which is a decrease of blood flow in the arteries of the limb. CLI results in resting pain, ulcers, gangrene, and limb loss. The outcome for patients with CLI is poor. Within 3 months of onset, 12% of patients will require an amputation (removal of part of the limb) and 9% will die of major cardiovascular events (heart attack or stroke). Percutaneous angioplasty (PTA), a procedure used to open the blockages in blood flow, has become the first-line treatment for CLI given its effectiveness, lower cost, and lower risk of complications. However, 40% of patients will have re-narrowing of the arteries (restenosis) following the PTA procedure. This is thought to happen in part due to build up of blood cells called platelets which can also lead to the formation of blood clots. In order to try to avoid this problem, most patients are prescribed a combination of two blood thinning medications, acetylsalicylic acid (ASA or aspirin) and clopidogrel (the brand name is Plavix).
The purpose of this study is to determine if a new blood thinner called rivaroxaban, given in combination with aspirin, would be more effective in preventing re-narrowing of the arteries than the current standard of care (aspirin and clopidogrel).
Rivaroxaban is a pill and does not require blood test monitoring. It has been approved by Health Canada for use in prevention of blood clots in patients undergoing hip or knee surgery and to treat patients with blood clots in their legs and lungs. Low dose aspirin has been approved for reducing the risk of heart attacks and strokes. These medications have not been tested together in patients for prevention of re-narrowing of their arteries
This is a pilot study conducted at one center, The Ottawa Hospital.
It is a Phase 2 open label randomized controlled trial.
Following the PTA procedure, once all inclusion/exclusion criteria are met, the participant will be randomized into one of two groups:
- Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily OR
- Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
Visits will occur at 7 days, 30 days, 90 days, 6 months and 12 months. Participants will be followed for 12 months (± 14 days) in total. All adverse events will be collected for the duration of the study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent.
- •Infra-inguinal PAD presenting as CLI defined as a Rutherford category of 3, 4, or 5
- •More than 50% stenosis in the target infrainguinal vessel
- •Good candidates for PTA using POBA (plain old balloon angioplasty) with or without stenting defined as TASC a and b lesions.
Exclusion Criteria
- •Rutherford scale of 0,1,2 or 6
- •Acute limb-threatening ischemia (e.g. embolic disease)
- •Previous infrainguinal bypass or PTA procedures of the affected leg
- •Hybrid procedures
- •Creatinine clearance \<30 mL/min
- •Platelet count \<100x109/L
- •INR \>1.5; Hbg \<100 g/L
- •History of or condition associated with increased bleeding risk including, but not limited to:
- •Major surgical procedure or trauma within 30 days before the randomization visit
- •Clinically significant gastrointestinal bleeding within 6 months before the randomization visit
Arms & Interventions
clopidogrel plus aspirin
Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
Intervention: clopidogrel plus aspirin
rivaroxaban plus aspirin
Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily
Intervention: rivaroxaban plus aspirin
Outcomes
Primary Outcomes
Reintervention, Above Ankle Amputation and Restenosis (RAS)
Time Frame: 1 year
The primary outcome is a combined endpoint consisting of any Reintervention (surgical procedures to revascularize), Above ankle amputation and restenosis(recurrence of blockage in the vein) (RAS) at one year
Secondary Outcomes
- Number of Participants With 2 Class Improvement on the Rutherford Scale(1 year)
- Event-free Survival(1 year)
- Overall Survival(1 year)
- The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR)(1 year)
- TVR(1 year)
- Peri-procedure Death(30 days)
- MACE(1 year)
- Major Bleeding(90 days)
- Minor Bleeding(90 days)
- Biomarkers(90 days)