Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke

Not Applicable

Completed

• Conditions: Ischaemic stroke, transient ischaemic attack (TIA); Circulatory System; Transient cerebral ischaemic attacks and related syndromes

• Registration Number: ISRCTN47823388
• Lead Sponsor: niversity of Nottingham (UK)

Brief Summary

2015 Protocol article in http://www.ncbi.nlm.nih.gov/pubmed/26079743 protocol 2018 Results article in https://www.ncbi.nlm.nih.gov/pubmed/29274727 results 2018 Results article in https://www.ncbi.nlm.nih.gov/pubmed/30179153 results 2023 Results article in https://pubmed.ncbi.nlm.nih.gov/37474599/ (added 21/07/2023) 2023 Results article in https://doi.org/10.1016/j.conctc.2023.101186 Re-Assessment of the TARDIS trial (added 25/09/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2009-01-23
• Study Completion: 2017-09-30
• Last Update Posted: 9 October 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 5000

Inclusion Criteria

Current inclusion criteria as of 19/06/2014:
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 <24 hours with no residual symptoms and presenting with any of the following:
3.1. ABCD2 score >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 participant. If the participant is unable to give meaningful consent e.g. due to dysphasia, confusion, or reduced conscious level, proxy consent may be obtained from a relative, carer or legal representative.

Inclusion criteria from 25/03/2010 to 19/06/2014:
Adults at high risk of recurrent ischaemic stroke:
1. Acute non-cardioembolic ischaemic stroke (<48 hours of onset). All strokes must have motor weakness or dysphasia at the time of randomisation.
2. Acute TIA (<48 hours of onset) with one or more of: crescendo TIA (>1 TIA within 1 week), and/or admitted on dual antiplatelet t

Exclusion Criteria

Current exclusion criteria as of 19/06/2014:
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. 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
10. Definite need for glycoprotein IIb-IIIa inhibitors
11. Patients who have received thrombolysis within 24 hours
12. No enteral access
13. Pre-morbid dependency (mRS>2).
14. Severe high BP (BP >185/110 mmHg).
15. Haemoglobin less than 10 g/dL
16. Platelet count more than 600 x 109 /L or less than 100 x 109 /L
17. White cell count more than 30 x 109 /L or less than 3.5 x 109 /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. Concomitant STEMI or NSTEMI.
21. Stroke secondary to a procedure (e.g. carotid or coronary intervention)
22. Coma (GCS<8)
23. Non-stroke life expectancy <6 months
24. Dementia
25. 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)
26. 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.
27. Females of childbearing potential, pregnancy or breastfeeding
28. Patients who have not had post-thrombolysis neuroimaging.
29. Patients on aspirin and clopidogrel prior to the underlying event.

Exclusion criteria from 25/03/2010 to 19/06/2014:
1. Age <50
2. Motor weakness or dysphasia lasting <10 minutes
3. Pure sensory, vertigo or dizziness, speech or visual disturbance symptoms without weakness or dysphasia
4. Patients with contraindications to, or intolerance of, aspirin, clopidogrel or dipyridamole
5. Patients with definite need for treatment with clopidogrel (e.g. recent MI)
6. Pre-morbid dependency (mRS>2)
7. No enteral access
8. Parenchymal haemorrhagic transformation (PH I/II), subarachnoid haemorrhage or other non ischaemic cause for weakness
9. TIA not fulfilling inclusion criteria
10. Definite need for full dose or

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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.