E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Peripheral arterial disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | 1 |
E.1.2 | Classification code | 10062585 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal 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; - Patient aged > 40 years and < 80 years; - Chronic background treatment with daily ASA or Triflusal, whatever the dose, started at least 4 weeks before surgery. A window of a few days without ASA or Triflusal before surgery is acceptable, according to local practice. - 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. |
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E.4 | Principal exclusion criteria |
Patients having any of the following at randomization will not be included in the study:
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) - Patients undergoing, along with the below knee bypass any other surgical intervention (or who has undergone one within the last four weeks before surgery), except endovascular procedures of the opposite leg at the femoral level or below (cf note below). - Any aneurysm in or near the operated segment
Medical history related to bleeding risk - Current active bleeding at surgical site - Withdrawal of an epidural catheter less than 12 hours before randomization - Increased risk of bleeding, such as severe hepatic insufficiency, current peptic ulceration, proliferative diabetic retinopathy, history of severe systemic bleeding (e.g. gastrointestinal bleeding, gross hematuria, intraocular bleeding, hemorrhagic stroke or intracranial hemorrhage) or other history of bleeding diathesis or coagulopathy.
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 - High probability of death of non-cardiovascular cause, within the next 12 months. - History of clinically significant or persistent thrombocytopenia or current platelet count less than 120 G/L - History of clinically significant or persistent neutropenia or current neutrophil count less than 1.8 G/L - Pregnant women , or women of childbearing potential who are not following an effective method of contraception.
Recent or planned medical therapy - Thrombolytic therapy within 24 hours prior to randomization, or use of GPIIb/IIIa receptor antagonist within 4 days prior to randomization - Hypersensitivity to the drug substance or any component of the product - Associated condition requiring chronic use of oral anticoagulants (e.g. warfarin, ximelagatran) or antiplatelet agents (including dipyridamole, cilostazol, GPIIb/IIIa antagonists, ticlopidine, clopidogrel or ASA>100mg/d)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is defined as the first occurrence, over the duration of follow-up (randomization to month 24 (728 days)/study end date), of: - Occlusion of the index bypass graft documented by any imaging procedure (e.g. angiography, Duplex scanning) or - Any revascularization procedure on the index bypass graft or para-anastomotic region, defined as 2 cm proximal or distal to the bypass graft anastomosis (graft replacement or endovascular intervention), OR - Amputation above the ankle of the affected limb or - Death This primary outcome will be assessed using the ITT ( Intent-to-treat) population and per protocol population.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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event-driven trial (193 expected events) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 24 |