E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ischaemic stroke and TIA (transient ischaemic attack) |
Iskæmisk apopleksi og TCI(transient cerebral iskæmi) |
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E.1.1.1 | Medical condition in easily understood language |
Stroke due to blood clot. |
Blodprop i hjernen |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042244 |
E.1.2 | Term | Stroke |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10044390 |
E.1.2 | Term | Transient ischaemic attack |
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 |
To assess the safety of short-term administration (1 month) of intensive antiplatelet therapy (aspirin, dipyridamole and clopidogrel) versus current guideline therapy (dual aspirin and dipyridamole, or clopidogrel monotherapy) in patients with very recent ischaemic stroke or TIA. |
At undersøge sikkerhed ved kort-tids administration (30 dage) af intensiv pladehæmmerbehandling (ASA, dipyridamol og clopidogrel) versus aktuelt anbefalet behandling (ASA + dipyridamol eller clopidogrel) hos patienter med iskæmsik apopleksi eller TCI indenfor 48 timer. |
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E.2.2 | Secondary objectives of the trial |
1. To assess the safety of short-term administration (1 month) of intensive antiplatelet therapy versus guideline therapy in patients with very recent ischaemic stroke or TIA.
2. To further assess, in high risk patients with stroke/TIA, whether: ii. it is feasible to administer intensive therapy acutely and is tolerable to take for 1 month, iii. intensive therapy is superior in respect of surrogate markers such as platelet function. iv. intensive therapy improves functional outcome
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1. at undersøge sikkerhed ved korttidsadministration (30 dage) af intensiv pladehæmmer behandling versus vanlig anbefalet behandling hos patienter med iskæmisk apopleksi eller TCI indenfor 48 timer |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Adults at high risk of recurrent ischaemic stroke: 1. Acute high risk TIAs <48 hours of onset All TIAs must have limb weakness and/or dysphasia lasting at least 10 minutes. 2. Ischaemic, non cardioembolic stroke with limb weakness, dysphasia or hemianopia ≤48 hours of onset with neuroimaging to rule out alternative causes. 3. Meaningful consent, or consent from a relative, carer or legal representative if the patient is unable to give consent (e.g. in cases of dysphasia, confusion, or reduced conscious level).
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Voksne med høj risiko for fornyet apopleksi: 1. Akut høj-risiko TCI < 48 timer efter debut; der skal have været mindst 10 min varende kraftnedsættelse og/eller afasi. 2. Iskæmisk, ikke kardio-embolisk apopleksi med kraftnedsættelse, afasi, eller hemianopsi med debut indenfor 48 timer og billediagnostik i overensstemmelse hermed. 3. Informeret samtykke fra patient eller stedfortrædende samtykke, hvis patienten ikke selv på grund af apopleksi-symptomer kan afgive samtykke..
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E.4 | Principal exclusion criteria |
1. Age<50 2. Isolated sensory symptoms or vertigo/dizziness or facial weakness 3. Isolated hemianopia without positive neuroimaging evidence 4. Intracranial haemorrhage 5. Baseline neuroimaging showing parenchymal haemorrhagic transformation (PH I/II) of infarct, subarachnoid haemorrhage or other non ischaemic cause for symptoms 6. Presumed cardioembolic stroke (e.g. history or current AF, myocardial infarction within 3 months) 7. Participants with contraindications to, or intolerance of, aspirin, clopidogrel or dipyridamole. 8. Participants with definite need for treatment with aspirin, clopidogrel or dipyridamole individually or in combination (e.g. aspirin and clopidogrel for recent MI/acute coronary syndrome) 9. Participant has taken clopidogrel or dipyridamole after the index event but prior to randomisation (aspirin is allowed between ictus onset and randomisation) 10. Definite need for full dose oral (e.g. warfarin, dabigatran) or medium to high dose parenteral (e.g. heparin) anti-coagulation. NB Low dose heparin for DVT prophylaxis is allowed 11. Definite need for glycoprotein IIb-IIIa inhibitors 12. Received thrombolysis within the last 24 hours 13. No enteral access 14. Pre-morbid dependency (mRS>2). 15. Severe high BP (BP>185/110 mmHg). 16. Haemoglobin less than 10g/dL 17. Platelet count more than 600 x 109 /L or less than 100 x 109 /L 18. White cell count more than 30 x 109 /L or less than 3.5 x 109 /L 19. Major bleeding within 1 year (e.g. peptic ulcer, intracerebral haemorrhage). 20. Planned surgery during 3 month follow-up (e.g. carotid endarterectomy) 21. Concomitant STEMI or NSTEMI. 22. Stroke secondary to a procedure (e.g. carotid or coronary intervention) 23. Coma (GCS<8) 24. Non-stroke life expectancy<6 months 25. Dementia 26. Participation in another drug or devices trial concurrently or within 30 days. (participants may take part in observational studies or non-drug or devices trials) 27. Geographical or other factors that may interfere with follow-up e.g. no fixed address or telephone contact number, not registered with a GP, or overseas visitor. 28. Females of childbearing potential, pregnancy or breastfeeding
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1. Alder < 50 år 2. Isolerede sensoriske symptomer, vertigo/svimmelhed eller ansigtslammelse 3. Isoleret hemianopsi uden tegn til infarkt på billediagnostik 4. Intrakraniel blødning. 5. Baseline billediagnostil visende parenkymatøs hæmoragisk transformation (PHI/PHII) af infarkt, SAH eller anden ikke iskæmisk årsag til symptomerne. 6. Antaget kardio-embolisk apopleksi (fx kendt AF eller AMI indenfor 3 måneder) 7. Patienter med kontraindikation mod ASA, clopidogrel eller dipyridamol. 8. Patienter med absolut indikation for behandling med specifikt ASA, dipyridamol eller clopidogrel (fx ASA og clopidogrel pga nyeligt AMI/AKS) 9. Patienten har fået clopidogrel eller dipyridamol efter index event men før randomisering (ASA er tilladt mellem debut og randomisering) 10. Indikation for oral AK-behandling (fx warfarin, Pradaxa, Xarelto) eller meduim eller højdosis parenteral AK-behandling (fx heparin). Lav-dosis heparin til DVT profylaxe er tilladt.
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E.5 End points |
E.5.1 | Primary end point(s) |
The trial will assess ordinal stroke severity: 5-level ordinal stroke and TIA scale with stroke ordered by its severity using the modified Rankin Scale (mRS): fatal stroke / severe non-fatal stroke (mRS 2-5) / mild stroke (mRS 0,1) / TIA / no stroke-TIA, measured at 90 days. |
Dette studie vil bedømme sværhedsgrad efter apopleksi som ordinalskala-data ved hjælp af modified Rankin Scale (mRS): død/svær apopleksi (mRS 2-5)/mild apopleksi (mRS 0-1)/TCI/ingen apopleksi/TCI opgjort efter 90 dage. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
3 months after stroke - is analysed at end of trial |
3 måneder efter debut af apopleksi/TCI - analyseres ved end of trial |
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E.5.2 | Secondary end point(s) |
1. Safety outcome - bleeding at 35 days (end of treatment). 2. Functioning, cognition and quality of life. |
1. Sikkerhed: enhver blødning indenfor 35 dage. 2. funktions-niveau, kognition og livskvalitet. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Safety outcome - bleeding. Interim analysis at 4 years and end of trial at 8 years and 3 months. 2. Functional cognition, QUOL outcomes - 8 years 3 months. |
1.Sikkerhed - blødning. Interim analyse planlægges efter 4 år, og ved end of trial efter 8 år og 3 måneder. 2. Funktionsniveau, kognition og livskvalitet - efter 8 år og 3 måneder. |
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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 | 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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 |
blindet outcome evaluering |
Outcome assessment blinded |
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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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 200 |
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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As per protocol |
Som beskrevet i protokollen |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |