Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke "TARDIS"

Terminated

Phase 3 Results N/A

Trial Description

The risk of recurrence is greatest immediately after stroke or Transient Ischaemic Attack (TIA). Existing prevention strategies (antithrombotic, lipid/blood pressure lowering, endarterectomy) reduce, not abolish, further events. Dual antiplatelet therapy - aspirin & clopidogrel (AC) for IHD, aspirin & dipyridamole (AD) for stroke, is superior to aspirin monotherapy. The investigators hypothesise that triple antiplatelet therapy (ACD) will be superior to AD in patients at high-risk of recurrence, providing bleeding does not become excessive.
Design: TARDIS is a multicentre, parallel-group, prospective, randomised, open-label, blinded-endpoint, controlled trial. In the start-up phase, the investigators will assess over 3 years the safety, tolerability and feasibility of intensive therapy (ACD) versus guideline therapy (AD) given for 1 month in 750 patients with acute stroke/TIA. The main phase will then assess the safety and efficacy of ACD in up to 3500 patients. The primary outcome is ordinal stroke (fatal/severe non-fatal/mild/TIA/none) at 90 days. Secondary outcomes include death, MI, vascular events, function, bleeding, serious adverse events; sub-studies will assess cerebral emboli and platelet function.

Detailed Description

2.1 Purpose To perform a randomised trial assessing the efficacy, safety and tolerability of intensive antiplatelet therapy (Asp+Dip+Clop) versus guideline antiplatelet therapy (Asp+Dip or Clop) in patients with recent ischaemic stroke or TIA and who are at high risk of recurrence.
2.2 Primary Objective To assess ordinal stroke severity at 90 days after short-term administration (1 month) of intensive antiplatelet therapy versus guideline therapy in patients with very recent ischaemic stroke or TIA.
2.3 Secondary Objectives
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

Trial Stopped: Trial reached a definitive answer ahead of full recruitment.

Conditions

Interventions

  • Aspirin, Dipyradimole, Clopidogrel Drug
    Other Names: Aspirin; Dipyradimole; Clopidogrel
    Intervention Desc: Participants in the intensive antiplatelet group will receive Asp+Dip+Clop triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days.
    ARM 1: Kind: Experimental
    Label: Intensive antiplatelet therapy
    Description: Participants in the intensive antiplatelet group will receive Aspirin+Dipyridamole+Clopidogrel triple therapy for 28-30 days (to cover the period of maximum risk of recurrence) along with standard 'best care' (including lifestyle advice, BP and lipid lowering). Clop will be given as a loading dose of 300 mg,12 then 75 mg daily, Asp as a loading dose of 300 mg,22 then 75 mg daily, and Dip modified release 200 mg twice daily 9 for 28-30 days.

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Subject)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary outcome is ordinal stroke severity at 90 days 90 days Yes
Secondary Safety 90 days Yes
Secondary Serious adverse events 90 Days Yes
Secondary Death 90 days Yes
Secondary Platelet function. 90 Days Yes

Sponsors