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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Reintervention, Above Ankle Amputation and Restenosis (RAS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •History of intracranial, intraocular, spinal, or atraumatic intra-articular bleeding
- •Chronic hemorrhagic disorder
- •Known intracranial neoplasm, arteriovenous malformation, or aneurysm
- •Sustained uncontrolled hypertension: systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg
- •Severe, disabling stroke (modified Rankin score of 4 to 5, inclusive) within 3 months or any stroke within 14 days before the randomization visit
- •Aspirin in combination with thienopyridines within 5 days before randomization
- •Intravenous antiplatelets within 5 days before randomization
- •Fibrinolytics within 10 days before randomization
- •Known HIV infection at time of screening
- •Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis or ALT >3ULN)
- •Childbearing potential without proper contraceptive measures, pregnancy or breast feeding
- •Drug addiction or alcohol abuse within 12 months before the randomization visit
- •Systemic treatment with strong CYP 3A4 and P-glycoprotein inhibitors : such as ketoconazole, itraconazole, posaconazole, or ritonavir
- •Known allergy or hypersensitivity to any component of rivaroxaban, ASA or clopidogrel
- •Need for long term anticoagulation or double antiplatelet agents other than PAD such as atrial fibrillation, heart valve replacement, acute coronary syndrome, stroke or venous thromboembolism
- •Anticipated need for chronic (> 4 weeks) therapy with non-steroidal anti-inflammatory drugs.
- •Concomitant treatment with any other anticoagulant, including oral anticoagulants, such as warfarin, dabigatran, apixaban, except under circumstances of switching therapy to or from study treatment.
- •Inability to adhere to protocol.
- •Severe concomitant condition or disease (e.g. life expectancy <6 months secondary to cancer, advanced liver disease or dementia)
研究组 & 干预措施
clopidogrel plus aspirin
Clopidogrel 75 mg daily X 90 days plus ASA 81 mg daily
干预措施: clopidogrel plus aspirin (Drug)
rivaroxaban plus aspirin
Rivaroxaban 2.5 mg BID X 90 days plus ASA 81 mg daily
干预措施: rivaroxaban plus aspirin (Drug)
结局指标
主要结局
Reintervention, Above Ankle Amputation and Restenosis (RAS)
时间窗: 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
次要结局
- 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)