CASPAR : Clopidogrel and Acetyl Salicylic Acid in Bypass Surgery for Peripheral ARterial Disease

A Double-blind, Randomized Study of Clopidogrel 75 mg/d vs Placebo, on a Background of ASA 75-100 mg/d,in Peripheral Arterial Disease (PAD) Patients Receiving a Unilateral Below Knee Bypass Graft.

Primary objective:

To evaluate whether clopidogrel 75 mg o.d. versus placebo (on a background of ASA 75-100 mg/d) will lead to an increased rate of primary patency, limb salvage and survival, in patients receiving a below knee bypass graft for the treatment of PAD.

Secondary objectives:

Comparison, between the two treatment groups, of :

• Primary patency,
• Assisted primary patency,
• Cardiovascular death / myocardial infarction / stroke / any amputation above the ankle.
• Ankle Brachial Pressure Index (ABPI) changes from baseline

Inclusion Criteria: A patient is eligible for inclusion in the study 2-4 days after surgery if all the following criteria are fulfilled:

• Informed consent obtained;
• Chronic background treatment with daily ASA, whatever the dose, started at least 4 weeks before surgery. A window of a few days without ASA before surgery is acceptable, according to local practice. Post-randomization use of ASA must be between 75 and 100 mg/day.
• Unilateral below knee bypass graft (i.e. the distal anastomosis is below the level of the knee joint) for atherosclerotic PAD within the previous 4 days;
• Demonstration of initial patency of the index graft by an objective measurement (e.g. intra-operative Doppler scanning, flow measurement, angiography, Duplex scanning) during bypass surgery, or between surgery and the time of randomization;
• No clinical evidence of graft occlusion at time of randomization.

Exclusion criteria :

PAD medical/surgical history

• Onset of PAD symptoms before the age of 40 years
• Non-atherosclerotic vascular disease (e.g. Buerger's disease, popliteal entrapment syndrome)
• Patient receiving aorto-bifemoral, iliac-femoral or crossover (femoral-femoral) grafts, or undergoing peripheral transcutaneous angioplasty (PTA), with or without stenting, during the same surgery.

Medical history related to bleeding risk

• Current active bleeding at surgical site
• Withdrawal of an epidural catheter less than 12 hours before randomization
• Current active bleeding or increased risk of bleeding, such as severe hepatic insufficiency, proliferative diabetic retinopathy, peptic ulceration, bleeding diathesis or coagulopathy
• Peptic ulceration within 12 months of randomization
• Previous or current intracranial hemorrhage or hemorrhagic stroke, or any previous stroke for which the diagnosis of hemorrhagic stroke cannot be excluded
• Any history of severe spontaneous bleeding such as gastrointestinal bleeding, gross hematuria, intraocular bleeding

Other medical conditions

• Previous disabling stroke (severe cerebral deficit such that the patient is bedridden or demented)
• NYHA Class IV heart failure
• Uncontrolled hypertension: Systolic Blood Pressure (SBP) > 180 mm Hg, or Diastolic Blood Pressure (DBP) > 100 mm Hg