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.
- Clopidogrel (Plavix®)Drug
Other Names: Plavix Intervention Desc: Antiplatelet agent
- Dipyridamole (Persantine®)Drug
Intervention Desc: Platelet aggregation inhibitor
- Aspirin Drug
Other Names: Aspirin at bedtime Intervention Desc: Antiplatelet agent; inhibits thromboxane A2; antipyretic
Multicentre parallel group prospective randomised open-label blinded-endpoint controlled trial.
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.
|Type||Measure||Time Frame||Safety Issue|
|Primary||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||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.|