TARDIS
Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke
|
Status:
Ongoing. The planned start date is March 2009. The start-up phase will recruit patients from 20 hospitals in the
Trent and South-East Stroke Local Research Networks of the UK Stroke Research Network.
Purpose:
To perform a randomised trial assessing the efficacy, safety and tolerability of adding clopidogrel to aspirin and dipyridamole in patients with recent ischaemic stroke or transient ischaemic attack (TIA) and who are at high risk of recurrence.
Interventions:
Aspirin
Antiplatelet agent; inhibits thromboxane A2; antipyretic
|
Clopidogrel
Antiplatelet agent
|
Dipyridamole
Platelet aggregation inhibitor
|
Location(s):
United Kingdom
Year Started:
2009
Design:
Multicentre parallel group prospective randomised open-label blinded-endpoint controlled trial.
Inclusion Criteria
Adults of either sex at high risk of recurrent ischaemic stroke:
1. Acute non-cardioembolic ischaemic stroke (less than 48 hours of onset)
2. Acute TIA (less than 48 hours of onset) with one or more of: crescendo TIA (greater than one TIA within 1 week), and/or admitted on dual antiplatelet therapy (aspirin/dipyridamole, aspirin/clopidogrel, clopidogrel/dipyridamole), and/or with an ABCD2 score greater than 5 (stroke rate at 13 weeks greater than 10%)
Exclusion Criteria
Motor weakness lasting less than 30 minutes (pure sensory, vertigo or dizziness, speech or visual disturbance symptoms without weakness are excluded); patients with contraindications to, or intolerance of, aspirin, clopidogrel or dipyridamole; pre-morbid dependency (modified Rankin Scale [mRS] greater than 3); no enteral access;
parenchymal haemorrhagic transformation (PH I/II), subarachnoid haemorrhage or other non-ischaemic cause for weakness; TIA not fulfilling inclusion criteria; definite need for, or currently on triple antiplatelet therapy or anticoagulation; indication for, or received (in last week), thrombolysis; presumed cardioembolic stroke (e.g. atrial fibrillation [AF], recent MI, or other conditions need for anticoagulation); severe high blood pressure (BP) (greater than 185/110 mmHg); bleeding within 1 year (e.g. peptic ulcer, intracerebral haemorrhage); planned surgery during 3 month follow-up (e.g. carotid endarterectomy); concomitant acute coronary syndrome; stroke secondary to a procedure (e.g. carotid or coronary intervention); planned surgery during first month post stroke (e.g. carotid endarterectomy); Coma (Glasgow Coma Scale [GCS] less than 8); non-stroke life expectancy less than 6 months; Dementia;
participation in another drug trial concurrently or within 30 days (patients may be randomised into observational studies or non-drug trials); not available for follow-up, e.g. no fixed address, overseas visitor; females of childbearing potential, pregnancy or breastfeeding.
Patient Involvement:
Patients will be randomized to triple (ACD) vs dural (AD) therapy for stroke prophylaxis given for 1 month. Patients will have: 1. Transcranial Doppler: TCD recordings will be performed from the middle cerebral artery (MCA) at baseline and day 3 ± 1 and 2. Platelet function: Platelet expression of P-selectin will be used to monitor platelet effects in patients. Blood will be taken from all patients at baseline and day 7 ± 1.
Primary Outcome:
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 Outcome:
Secondary outcomes at 35 and 90 days: Binary stroke, Ordinal stroke (fatal stroke/non-fatal stroke/no stroke), Binary myocardial infarction; Ordinal myocardial infarction (fatal MI/non-fatal MI/no MI); Binary composite vascular outcome (non fatal MI and stroke, vascular death); Ordinal composite vascular outcome; Composite stroke, TIA, acute coronary syndromes and all cause death
Secondary outcomes at 90 days: Function (modified Rankin Scale [mRS], Barthel Index); Cognition (Telephone Interview for Cognitive Status [TICS]/animal naming); Quality of life (EuroQoL/EQ-5D instrument); Mood (Zung), disposition (home, institution, dead), days at home, economic activity.
Tolerability: Proportion of patients completing 28 days of randomised treatment; feasibility: Recruitment rate per week; Safety measures at 35 and 90 days: death, binary major bleeding (fatal, symptomatic, causing fall in haemoglobin of greater than 2 g/l, or leading to transfusion of greater than 2 units of blood/red cells), binary minor bleeding (e.g. bruising), binary all bleeding, symptomatic intracerebral haemorrhage, major extracranial bleeding, binary serious adverse events, ordinal adverse events (fatal/serious/other/none), full blood count (at 35 days)
thrombotic thrombocytopenic purpura, Granulocytopenia.
|
Source of Information:
Presented at the 2009 International Stroke Conference (February 2009).
Current Controlled Trials
|
Web Links and Publications:
|
|
This information last updated on: 10/14/2009
Reviewed on: 10/14/2009.
|
Trials
Directories