Clinical trial NCT00174759: CASPAR : Clopidogrel and Acetyl Salicylic Acid in Bypass Surgery for Peripheral ARterial Disease
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Arterial Occlusive Diseases
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Bristol-Myers Squibb
First posted: 2005-09-15
Enrollment: 1460
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: 1st occurrence over the duration of follow-up of : index bypass graft occlusion based on imaging procedure, or graft replacement or endovascular intervention, or amputation above the ankle of the affected limb or death
Secondary outcomes:
measure: 1st occurrence of any component of following cluster of events : index bypass graft occlusion,any revascularization procedure or amputation. Change in ABPI.
Other outcomes:
Locations:
city: North Ryde
country: Australia
facility: Sanofi-Aventis
city: Vienna
country: Austria
facility: Sanofi-Aventis
city: Brussels
country: Belgium
facility: Sanofi-Aventis
city: Helsinki
country: Finland
facility: Sanofi-Aventis
city: Paris
country: France
facility: Sanofi-Aventis
city: Berlin
country: Germany
facility: Sanofi-Aventis
city: Budapest
country: Hungary
facility: Sanofi-Aventis
city: Milan
country: Italy
facility: Sanofi-Aventis
city: Gouda
country: Netherlands
facility: Sanofi-Aventis
city: Warsaw
country: Poland
facility: Sanofi-Aventis
city: Barcelona
country: Spain
facility: Sanofi-Aventis
city: Stockholm
country: Sweden
facility: Sanofi-Aventis
city: Meyrin
country: Switzerland
facility: Sanofi-Aventis
city: Guildford
country: United Kingdom
facility: Sanofi-Aventis
Study officials:
affiliation: Sanofi
name: Luc Sagnard
role: STUDY_DIRECTOR
References:
citation: Belch JJ, Dormandy J; CASPAR Writing Committee; Biasi GM, Cairols M, Diehm C, Eikelboom B, Golledge J, Jawien A, Lepantalo M, Norgren L, Hiatt WR, Becquemin JP, Bergqvist D, Clement D, Baumgartner I, Minar E, Stonebridge P, Vermassen F, Matyas L, Leizorovicz A. Results of the randomized, placebo-controlled clopidogrel and acetylsalicylic acid in bypass surgery for peripheral arterial disease (CASPAR) trial. J Vasc Surg. 2010 Oct;52(4):825-33, 833.e1-2. doi: 10.1016/j.jvs.2010.04.027. Epub 2010 Aug 1.