Ischaemic stroke, transient ischaemic attack (TIA) Circulatory System Transient cerebral ischaemic attacks and related syndromes
Conditions
Interventions
Current interventions as of 19/06/2014:
Intensive versus guideline antiplatelet therapy will be given for 28 to 30 days along with standard 'best care' (including lifestyle advice, BP and lipid loweri
Sponsors
University of Nottingham (UK)
Eligibility
Sex/Gender
All
Age
50 Years to 110 Years
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 25/06/2025: 1. Age =50 years 2. Event to randomization =48 h (24–48 h if thrombolysed) 3. Index event is a TIA with: 3.1. Resolved limb weakness and/or dysphasia 3.2. Duration 10 min to 24 h after onset (i.e. resolution between 24 h and randomization) 3.3. ABCD2 score =4; AND/OR crescendo TIA; AND/OR already on dual antiplatelet therapy 4. Index event is a non-cardioembolic ischemic stroke with: 4.1. Ongoing limb weakness OR ongoing facial weakness with resolved limb weakness; AND/OR dysphasia; AND/OR ongoing isolated hemianopia (with positive neuroimaging evidence showing ischemic stroke in occipital lobe); AND duration =1 hour 4.2. Resolved limb weakness; AND/OR dysphasia; AND duration >24 h after onset (i.e. resolution between 24 h and randomization) 5. Willing and able to provide written informed consent; proxy consent is acceptable if patients are dysphasic or confused, in accordance with the practice of the local site Previous inclusion criteria from 19/06/2014 to 25/06/2025: Adults at high risk of recurrent ischaemic stroke: 1. Age =50 years 2. Within 48 hours of ictus (24-48 hours if thrombolysed) 3. TIA with limb weakness and/or dysphasia lasting between 10 minutes and 4 3.2. Crescendo TIA 3.3. Already on dual antiplatelet therapy with aspirin and dipyridamole 3.4. Positive neuroimaging evidence to support the new event, ischaemic stroke on MR diffusion imaging Notes: 1. Patients who are on monotherapy e.g. aspirin alone, or clopidogrel alone, or dipyridamole alone, are eligible for recruitment. Similarly, patients who are on combined therapy aspirin + dipyridamole, are eligible for recruitment if they fulfil the above criteria. 2. Patients with posterior fossa events are eligible if they fulfil the above criteria. 3. Neuroimaging is not necessary for transient ischaemic attack. Crescendo TIA is >1 TIA in 1 week and the onset time of last TIA is taken as time of ictus. 4. Ischaemic non-cardioembolic stroke presenting with any of the following: 4.1. Ongoing limb weakness of more than 1 hour duration; and/or 4.2. Ongoing dysphasia of more than 1 hour duration; and/or 4.3. Resolved limb weakness of more than 1 hour duration with ongoing facial weakness; and/or 4.4. Ongoing isolated hemianopia of more than 1 hour duration with positive neuroimaging evidence to support the new event (e.g. ischaemic stroke in the occipital lobe) and/or 4.5. Limb weakness that resolves between 24-48 hours after onset; and/or 4.6. Dysphasia that resolves between 24-48 hours after onset; and/or 4.7. Positive neuroimaging to support the new ischaemic event with MR diffusion. 4.8. Already on combined dual antiplatelet therapy (aspirin + dipyridamole) Neuroimaging is essential for ischaemic stroke to exclude intracranial haemorrhage and a non-stroke diagnosis. If the patient received thrombolysis, a post-thrombolysis/pre-TARDIS scan needs to be done to exclude new thrombolysis-associated bleeding prior to enrolment. Typically, this is done routinely as 'standard of care', but if it is not done, then it must be done prior to enrolment. 5. Patients thrombolysed for stroke with full recovery in less than 24 hours from the onset of symptoms are eligible for inclusion providing neuroimaging post-thrombolysis excludes intracranial haemorrhage. 6. Informed consent from the participant. If the participant is unable to give mea
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 25/06/2025: 1. Isolated sensory symptoms, facial weakness, or vertigo/dizziness 2. Isolated hemianopia without positive neuroimaging evidence 3. Intracranial haemorrhage 4. Baseline neuroimaging shows intracranial haemorrhage or parenchymal haemorrhagic transformation (PH 1 or 2) of infarct, subarachnoid haemorrhage, or other non-ischemic cause for symptoms 5. Presumed cardioembolic stroke (e.g. history of current atrial fibrillation (AF), myocardial infarction 2) 12. Severe high BP (BP >185/110 mmHg) 13. Haemoglobin 600 x 10e9/L 15. White cell count 30 x 10e9/L 16. Major bleeding within 1 year (e.g. peptic ulcer, intracerebral haemorrhage) 17. Planned surgery in next 3 months (e.g. known need for carotid endarterectomy) 18. Concomitant acute coronary syndrome (e.g. ST segment elevation myocardial infarction [STEMI] or non-STEMI [NSTEMI]) 19. Stroke secondary to a procedure (e.g. carotid or coronary intervention) 20. Coma (Glasgow Coma Scale [GCS] 2) 14. Severe high BP (BP >185/110 mmHg) 15. Haemoglobin less than 10 g/dL 16. Platelet count more than 600 x 10e9 /L or less than 100 x 10e9 /L 17. White cell count more than 30 x 10e9 /L or less than 3.5 x 10e9 /L 18. Major bleeding within 1 year (e.g. peptic ulcer, intracerebral haemorrhage) 19. Planned surgery during 3-month follow-up (e.g. carotid endarterectomy) 20. Concomita
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measure as of 25/06/2025: 1. Frequency and severity of recurrent strokes and TIA using information from the follow-up call at Day 90 2. Severity of stroke measured using modified Rankin Scale (mRS) at Baseline and Day 90 Previous primary outcome measure: The trial will assess ordinal stroke severity at 90 days, assessed as a level ordinal outcome: mRS 6 = fatal-5-4-3-2-1-0-TIA-no stroke; this approach allows for smaller sample sizes than for binary outcomes such as stroke/no stroke. The start-up phase will also assess ordinal bleeding (fatal/major/minor/none) at 35 days (end of treatment) as adjudicated by an independent blinded panel. | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 25/06/2025: 1. Headache that required treatment or led to discontinuation, using information from the medical notes at Day 7 and Day 35 2. Recurrent stroke or TIA, using information from the medical notes at Day 7 and Day 35 3. Stroke impairment and neurological deterioration, measured using the National Institutes of Health Stroke Scale (NIHSS) at Baseline, Day 7 and Day 35 4. Composite vascular event, using information from the medical notes and follow-up call at Day 7, Day 35 and Day 90 5. Venous thromboembolism, using information from the medical notes and follow-up call at Day 7, Day 35 and Day 90 6. Haemoglobin, using information from the medical notes at Day 7 and Day 35 7. Bleeding, using information from the medical notes and follow-up call at Day 7, Day 35 and Day 90 8. Myocardial infarction, using information from the medical notes and follow-up call at Day 7, Day 35 and Day 90 9. SAEs, using information from the medical notes and follow-up call at Day 7, Day 35 and Day 90 10. Headache that required treatment or led to discontinuation, using information from the medical notes at Day 7 and Day 35 11. Length of stay in hospital, using information from the medical notes and at time of discharge letter at discharge/death and follow-up call at Day 90 12. Discharge disposition (death/institution/home), using information from the medical notes and discharge letter at time of discharge/death 13. Ability to perform activities of daily living, measured using the Barthel Index (BI) using information from the medical history at baseline and follow-up call at Day 90 14. Quality of life and health utility score, measured using European Quality of Life-5 Dimensions (EQ-5D) using information from the follow-up call at Day 90 15. Quality of life, measured using the European Quality of Life Visual Analog Scale (EQ-VAS) using information from the follow-up call at Day 90 16. Telephone Mini-Mental State Examination measured using the | — |
Countries
Denmark, England, Georgia, New Zealand, United Kingdom
Outcome results
None listed