Pilot Study to Examine the Use of Rivaroxaban After Angioplasty for Critical Limb Ischemia (RIVAL-PAD)
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|ClinicalTrials.gov Identifier: NCT02260622|
Recruitment Status : Completed
First Posted : October 9, 2014
Results First Posted : November 22, 2019
Last Update Posted : December 4, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Critical Limb Ischemia||Drug: rivaroxaban plus aspirin Drug: clopidogrel plus aspirin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||October 2014|
|Actual Primary Completion Date :||June 2017|
|Actual Study Completion Date :||March 2019|
Active Comparator: clopidogrel plus aspirin
Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
Drug: clopidogrel plus aspirin
Clopidogrel 75 mg daily for 90 days (with a loading dose of 300 mg clopidogrel following PTA) and 81 mg of ASA daily for 90 days
Experimental: rivaroxaban plus aspirin
Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily
Drug: rivaroxaban plus aspirin
Rivaroxaban 2.5 mg twice daily for 90 days (rivaroxaban will be started 6 to 8 hours after the finalization of the procedure) and 81 mg of ASA daily for 90 days
Other Name: treatment arm
- 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
- Number of Participants With 2 Class Improvement on the Rutherford Scale [ Time Frame: 1 year ]
Clinical improvement defined as cumulative improvement of 2 classes of the Rutherford scale without the need for repeated TLR in surviving patients.
There are seven stages to consider. the lower the score the less severe the disease or condition.
Stage 0 - Asymptomatic Stage 1 - Mild claudication Stage 2 - Moderate claudication - The distance that delineates mild, moderate and severe claudication is not specified in the Rutherford classification, but is mentioned in the Fontaine classification as 200 meters.
Stage 3 - Severe claudication Stage 4 - Rest pain Stage 5 - Ischemic ulceration not exceeding ulcer of the digits of the foot Stage 6 - Severe ischemic ulcers or frank gangrene
- Event-free Survival [ Time Frame: 1 year ]Event-free survival How long a patient is alive without the need for any further intervention or vascular events.
- Overall Survival [ Time Frame: 1 year ]Overall survival. How long a patient is alive following the intervention.
- The Number of Patients Requiring Target Lesions Revascularization Between Day 1 and the Final Visit (TLR) [ Time Frame: 1 year ]Target lesion revascularization (TLR) between day 1 and final visit
- TVR [ Time Frame: 1 year ]Target vessel revascularization (TVR between day 1 and final visit)
- Peri-procedure Death [ Time Frame: 30 days ]The number of patients that die within 30 days of the revascularization procedure.
- MACE [ Time Frame: 1 year ]Cumulative rate of major adverse cardiovascular events between day 1 and final visit
- Major Bleeding [ Time Frame: 90 days ]Cumulative rate of major bleeding between day 1 and day 90
- Minor Bleeding [ Time Frame: 90 days ]Cumulative clinically relevant or minor bleeding between day 1 and day 90
- Biomarkers [ Time Frame: 90 days ]Biological plausibility by measuring coagulation changes and SMC proliferation markers within 7 and 90 days based on the following markers: D-dimer, soluble CD40/44 ligands, and ERK 1/2
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02260622
|The Ottawa Hospital|
|Ottawa, Ontario, Canada, K1Y4E9|
|Principal Investigator:||Esteban Gandara, MD||Ottawa Hospital Research Institute|
|Principal Investigator:||Prasad Jetty, MD||Ottawa Hospital Research Institute|