Triple Antiplatelets for Reducing Dependency After Ischaemic Stroke

NCT01661322 | Terminated Phase 3 DMC

• 2 other identifiers: 080932007-006749-42
• Study Type: interventional
• Target: 3,096
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke

Keywords

Acute ischaemic stroke; TIA

Outcome Measures

Primary Outcomes (1)

• The primary outcome is ordinal stroke severity at 90 days

  5-level ordinal stroke and TIA scale with stroke ordered by its severity using the modified Rankin Scale (mRS): fatal stroke / severe non-fatal stroke (mRS 2-5) / mild stroke (mRS 0,1) / TIA / no stroke-TIA, measured at 90 days.; this approach allows for smaller sample sizes compared to binary outcomes such as stroke/no stroke

  90 days

Secondary Outcomes (4)

• Safety

  90 days

• Serious adverse events

  90 Days

• Death

  90 days

• Platelet function.

  90 Days

Study Arms (2)

Intensive antiplatelet therapy

ACTIVE COMPARATOR

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.

Drug: Aspirin, Dipyradimole, Clopidogrel

Guideline antiplatelet therapy

NO INTERVENTION

This may be one or two antiplatelet drugs, as per standard treatment. Clopidogrel or aspirin and dipyridamole.

Interventions

Aspirin, Dipyradimole, Clopidogrel DRUG

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.

Also known as: Aspirin, Dipyradimole, Clopidogrel

Intensive antiplatelet therapy

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults at high risk of recurrent ischaemic stroke:
• Age ≥ 50 years
• Within 48 hours of ictus (24-48 hours if thrombolysed)
• 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
• ABCD2 score \> 4, or
• Crescendo TIA or
• Already on dual antiplatelet therapy
• Note: Neuroimaging is not necessary for transient ischaemic attack. Crescendo TIA is \> 1 TIA in one week and the onset time of last TIA is taken as time of ictus.
• Ischaemic non cardioembolic stroke presenting with any of the following
• Ongoing limb weakness and/or dysphasia of more than one hour duration
• Resolved limb weakness of more than one hour duration with ongoing facial weakness
• Ongoing isolated hemianopia of more than 1 hour duration with positive neuroimaging evidence to support the index event (e.g. ischaemic stroke in occipital lobe)
• Resolved limb weakness and/or dysphasia between 24-48 hours after index event onset
• Note: Neuroimaging is essential for ischaemic stroke to exclude intracranial haemorrhage and/or non stroke diagnosis
• 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.

You may not qualify if:

• Age \< 50
• Isolated sensory symptoms or vertigo/dizziness or facial weakness
• Isolated hemianopia without positive neuroimaging evidence
• Intracranial haemorrhage
• Baseline neuroimaging showing parenchymal haemorrhagic transformation (PH I/II) of infarct, subarachnoid haemorrhage or other non ischaemic cause for symptoms
• Presumed cardioembolic stroke (e.g. history or current AF, myocardial infarction within 3 months)
• Participants with contraindications to, or intolerance of, aspirin, clopidogrel or dipyridamole.
• 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)
• Participant has taken clopidogrel or dipyridamole after the index event but prior to randomisation (aspirin is allowed between ictus onset and randomisation)
• 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
• Definite need for glycoprotein IIb-IIIa inhibitors
• Received thrombolysis within the last 24 hours
• No enteral access
• Pre-morbid dependency (mRS \> 2).
• Severe high BP (BP \> 185/110 mmHg).

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

Nottingham University Hospitals NHS Trust

Nottingham, United Kingdom

Location

Related Links

• TARDIS Trial Website

MeSH Terms

Conditions

Stroke

Interventions

Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Philip Bath

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2012
• First Posted: August 9, 2012
• Study Start: April 1, 2009
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: June 11, 2018

Record last verified: 2018-06

Locations

GB (1)