E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks, amaurosis fugax or stroke and who presenting with microembolic signals. |
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E.1.1.1 | Medical condition in easily understood language |
Patients suffering from symptomatic carotid artery stenosis, transient ischemic attacks, amaurosis fugax or stroke and who presenting with microembolic signals. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007687 |
E.1.2 | Term | Carotid artery stenosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 |
Efficacy objectives are: • Assessment of incidence of microembolic signals (MES) by transcranial Doppler (TCD) examination (before and after treatment) • Rate of MES per hour (before and after treatment) • Cerebral lesion analysis by DWI-NMR • Assessment of neurological status (NIH Stroke Scale) • Clinical endpoints will be summarised cumulatively i.e. before treatment, after treatment, at 3 months and at 12 months. The following endpoints will be recorded: o Rate of all cause death o Rate of stroke-related death o Any TIA, amaurosis fugax or stroke including haemorrhagic stroke • Assessment of cardiovascular outcome including myocardial infarction and re-intervention up to 3 and 12 months
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main inclusion criteria • Male and female patients aged >18 years • Extracranial carotid artery stenosis (diagnosed by vascular duplex ultrasound peak flow or angiography) Lesions with ≥ 50 % stenosis according to the European Carotid Surgery Trial (ECST) criteria • TIA, amaurosis fugax or stroke within the last 30 days
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E.4 | Principal exclusion criteria |
• NIHSS score > 18 • Recent intracerebral haemorrhage by X-ray computed tomography (CT) or nuclear magnetic resonance (NMR) • Cardiac cause of embolisation (atrial fibrillation or other cardiac source e.g. artificial heart valves) • History of hypersensitivity, contraindication or serious adverse reaction to inhibitors of platelet aggregation, hypersensitivity to related drugs (cross-allergy) or to any of the excipients in the study drug • History or evidence of thrombocytopenia (<30.000/µl), bleeding diathesis or coagulopathy (pathological international normalised ratio (INR) or activated partial thrompoplastin time (aPTT)) • Thrombolysis within the last 48 hours • Relevant haemorrhagic transformation as determined by CT, NMR or anamnesis • Oral anticoagulation or dual anti-platelet therapy with aspirin or clopidogrel and other P2Y inhibitors at screening (3 days for dipyridamole extended release; 8 hours for tirofiban/Aggrastat) • Sustained hypertension (systolic BP >179 mmHg or diastolic BP >109 mmHg) • History of severe systemic disease such as terminal carcinoma, renal failure (or current creatinine >200 µmol/l), cirrhosis, severe dementia, or psychosis • Current severe liver dysfunction (transaminase level greater than 5-fold over upper normal range limit) • Active autoimmune disorder such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis or glomerulonephritis • Known atrial fibrillation or other clinically significant ECG abnormalities (at present)
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E.5 End points |
E.5.1 | Primary end point(s) |
Exploratory endpoints are: • Assessment of incidence of microembolic signals (MES) by transcranial Doppler (TCD) examination (before and after treatment) • Rate of MES per hour (before and after treatment) • Cerebral lesion analysis by DWI-NMR • Assessment of neurological status (NIH Stroke Scale) • Clinical endpoints will be summarised cumulatively i.e. before treatment, after treatment, at 3 months and at 12 months. The following endpoints will be recorded: o Rate of all cause death o Rate of stroke-related death o Any TIA, amaurosis fugax or stroke including haemorrhagic stroke • Assessment of cardiovascular outcome including myocardial infarction and re-intervention up to 3 and 12 months
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline to 1-2 days after treatment. |
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E.5.2 | Secondary end point(s) |
•Rate of MES per hour (before and after treatment) •Assessment of neurological status (NIH Stroke Scale) •Cerebral lesion analysis by DWI-NMR and correlation to neurological status (before and after treatment) •Clinical endpoints will be summarised cumulatively i.e. before treatment, 1 and 3 days after treatment, at 3 months and at 12 months. The following endpoints will be recorded: oRate of all cause death oRate of stroke-related death oAny TIA, amaurosis fugax or stroke including haemorrhagic stroke •Assessment of cardiovascular outcome including myocardial infarction and re-intervention up to 3 and 12 months
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to 3 months / 12 months. |
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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 | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
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 | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |