E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
the acute treatment of patients with TIA or minor stroke |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10008192 |
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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 assess the effects of a 3-month regimen of clopidogrel initiated with a loading dose (LD) of 300mg followed by 75mg/day combined with ASA 75mg/day during the first month versus a 3-month regimen of ASA 75mg/day alone on reducing the occurrence of new ischemic vascular events (clinical ischemic stroke, new ischemic infarction on brain MRI, myocardial infarction, or vascular death) in patients with acute TIA/minor stroke |
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E.2.2 | Secondary objectives of the trial |
To assess separately the effects of this clopidogrel regimen versus ASA alone on the incidence of: - New clinical ischemic vascular events (ischemic stroke/MI/vascular death) as a cluster and evaluated individually - New cerebral infarction(s) assessed by MRI To evaluate change in modified Rankin scale (continuous) and percentage with score 0-2 at last follow-up. To compare the safety of the two treatment regimens in terms of: - Severe or moderate bleeding (GUSTO definition) - Cerebral bleeding - Total mortality - AEs/SAEs To compare efficacy and safety by qualifying event, TIA vs. stroke. To compare efficacy and safety by time to randomization, <12 h vs. >12 h.
In further exploratory analysis, to evaluate change in NIHSS score and cognitive function among survivors.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female > or = 40 years 2) TIA (> or = 10 minutes) or minor acute ischemic stroke (NIHSS < or = 3 at time of randomization) that can be treated with study drug within 24 hours of symptoms onset 3) Informed consent signed 4) Brain MRI scan performed within 24 hours of symptoms onset and prior to randomization
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E.4 | Principal exclusion criteria |
Related to absolute contraindications to the use of clopidogrel and/or ASA: 1) History of drug allergy to thienopyridine derivatives or ASA 2) Severe uncontrolled hypertension despite treatment at the time of randomization 3) History of clinically significant or persistent thrompocytopenia 4) History of clinically significant or persistent neutropenia 5) Women of child-bearing potential who are not following an effective method of contraception 6) Women who are breast-feeding 7) Other contra-indication to the use of ASA (severe renal or hepatic insufficiency, severe cardiac failure, asthma) Related to concomitant or planned medication(s) / treatment(s): 8) Absolute indication for the use of open-label clopidogrel, ticlopidine, GPIIb IIIa receptor antagonists, thrombolytics, heparin therapy or oral anticoagulation. 9) Use of thrombolysis within 24 hours prior to randomization. 10) Current treatment (last dose given within 10 days before randomization) with GPIIb IIIa receptor antagonists, , heparin therapy or oral anticoagulation. 11) Absolute indication for higher dose of ASA (>75 mg/day) or ASA + dipyridamole 12) Current or planned daily treatment with NSAIDs 13) Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months (if clinically indicated, vascular imaging should be performed prior to randomization whenever possible.) Related to TIA/Stroke characteristics: 14) Diagnosis of hemorrhage, vascular malformation, tumor, abscess, or other major non-ischemic brain disease (e.g., multiple sclerosis plaque, major developmental anomaly) on baseline brain MRI 15) Pure sensory symptoms, pure vertigo or dizziness, or pure visual loss without evidence of acute infarction on MRI 16) Modified Rankin Score >2 at randomization 17) NIH Stroke Scale Score >3 at randomization 18) Presumed cardiac source of embolus (e.g. atrial fibrillation, prosthetic cardiac valves known or suspected endocarditis) Related to the presence of other medical problems that would either interfere with participation in the trial or lead to inability to complete the trial: 19) 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, symptomatic hemorrhagic stroke, or intracranial hemorrhage), or other history of bleeding diathesis or coagulopathy 20) Concomitant (or within previous month) myocardial infarction or unstable angina 21) Presence of a severe co-morbid condition such that the patient is not expected to survive 1 year or which could interfere with the assessment of outcomes 22) Scheduled for surgery requiring study drug cessation 23) Receipt of any investigational treatment (drug or device) within the previous 30 days 24) Geographic or social factors making study participation impractical 25) Patient unable to understand the full meaning of the informed consent
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoint: - Percentage of patients with a new ischemic vascular event, defined as any event of the following cluster: o New cerebral infarction on brain MRI o New clinical ischemic stroke o MI o Vascular death
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 161 |
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 | Yes |
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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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 | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |