E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Secondary prevention of small subcortical strokes |
Prevención secundaria de infartos subcorticales de pequeño tamaño |
|
E.1.1.1 | Medical condition in easily understood language |
Prevention of one sort of cerebral vascular stroke (small subcortical strokes) in patients who already suffered one before |
prevención de un tipo de infarto vascular cerebral (infarto subcortical de pequeño tamaño) en pacientes que han padecido uno anteriormente |
|
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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10063751 |
E.1.2 | Term | Ministroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
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 determine whether combination antiplatelet therapy consisting of aspirin (325 mg/d, enteric coated) plus clopidogrel (75 mg/d) is superior to aspirin (325 mg/d, enteric coated) for reducing recurrent stroke (the primary endpoint), cognitive decline and major vascular events. |
na |
|
E.2.2 | Secondary objectives of the trial |
To determine whether ?intensive? blood pressure lowering to a specific target range is superior to ?usual? hypertension management for reducing recurrent stroke, cognitive decline and major vascular events. |
na |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Limits: Levels of Inflammatory Markers in the treatment of stroke (an SPS3 sub-study)? versión 2.0 de fecha 25/08/04.
genetic substudy genético (versión en castellano) versión 1.0 de 1 de abril de 2011 |
Limits: Levels of Inflammatory Markers in the treatment of stroke (an SPS3 sub-study)? versión 2.0 de fecha 25/08/04.
genetic substudy genético (versión en castellano) versión 1.0 de 1 de abril de 2011 |
|
E.3 | Principal inclusion criteria |
One of the following lacunar stroke clinical syndromes (adapted from Fisher) lasting > 24 hrs: a. Pure motor hemiparesis (PMH) b. Pure sensory stroke c. Sensorimotor stroke d. Ataxic hemiparesis e. Dysarthria-clumsy hand syndrome f. Hemiballism g. PMH with facial sparing h. PMH with horizontal gaze palsy i. PMH with contralateral III palsy j. PMH with contralateral VI palsy k. Cerebellar ataxia with contralateral III palsy l. Pure dysarthria 2. Absence of signs or symptoms of cortical dysfunction such as aphasia, apraxia, agnosia, agraphia, homonymous visual field defect, etc. 3. No ipsilateral cervical carotid stenosis (?50%) by a reliable imaging modality done in an approved laboratory within 6 months of the qualifying S3, if hemispheric. 4. No major-risk cardioembolic sources requiring anticoagulation or other specific therapy. Minor-risk cardioembolic sources will be permitted if anticoagulation is not prescribed by the patient?s primary care physician. Major risk sourcesa: Minor risk sourcesc: ? Atrial fibrillation ? Mitral valve prolapse + myxomatous changes ? Mitral stenosis ? Mitral annular calcification ? Prosthetic cardiac valves ? Patent foramen ovaled ? Recent (< 3 mos transmural MI) ? Atrial septal aneurysm ? LV thrombus, especially if mobile or protruding ? LV wall abnormalities (without thrombus) ? Atrial myxomas ? Calcific aortic stenosis ? Infective endocarditis ? Non-ischemic dilating cardiomyopathiesb ? Marantic endocarditis aAssociated with a substantial absolute risk of stroke, firmly linked to an embolic mechanism bRisk varies with the type and severity cAssociated with a low or uncertain absolute risk of initial or recurrent stroke or are incompletely established as direct embolic source dIf associated with pulmonary hypertension with sustained right-to-left shunting and venous source of emboli, it is a major risk. |
na |
|
E.4 | Principal exclusion criteria |
Disabling stroke (Modified Rankin Scale ?4) 2. Previous intracranial hemorrhage (excluding traumatic) or hemorrhagic stroke 3. Age under 40 years 4. High risk of bleeding (e.g. recurrent GI or GU bleeding, active peptic ulcer disease, etc) 5. Anticipated requirement for long-term use of anticoagulants (e.g. recurrent DVT) or other antiplatelets 6. Prior cortical stroke (diagnosed either clinically or by neuroimaging), or prior cortical or retinal TIA 7. Prior ipsilateral carotid endarterectomy 8. Impaired renal function: characterized by estimated GFR < 40 9. Intolerance or contraindications to aspirin or clopidogrel (including thrombocytopenia, prolonged INR) 10. A score < 24 (adjusted for age and education; adapted from Crum et al, 1993; n = 18,056) |
na |
|
E.5 End points |
E.5.1 | Primary end point(s) |
First occurrence during follow-up of any stroke, including ischemic and hemorrhagic |
na |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
The impact of antiplatelet therapy on the rate of cognitive decline. The null hypothesis is that there will be no difference in the rate of cognitive decline among SPS3 participants assigned to receive aspirin alone vs. the combination of aspirin with clopidogrel. Analysis for the effects of therapy on cognitive function will be through assessing changes on repeated neuropsychological tests. The primary measure of cognitive function will be the Cognitive Assessment Screening Instrument. |
na |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | 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 | Yes |
E.8.1.7.1 | Other trial design description |
na |
2x2 factorial design, second intervention is open with PROBE assessment |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 9 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 |
Argentina |
Ecuador |
Spain |
United States |
|
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
|
|
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |