Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388)

Beridze, M.; Christensen, H.; Dineen, Robert A.; Duley, Lelia; Heptinstall, Stan; James, M.; Markus, H.S.; Pocock, S; Ranta, A.; Robinson, T.; Nikola, N.; Venables, G.; Bath, Philip M.W.

Abstract

RATIONALE:

The risk of recurrence following a stroke or transient ischemic attack is high, especially immediately after the event.
HYPOTHESIS:

Because two antiplatelet agents are superior to one in patients with non-cardioembolic events, more intensive treatment might be even more effective.
SAMPLE SIZE ESTIMATES:

The sample size of 4100 patients will allow a shift to less recurrence, and less severe recurrence, to be detected (odds ratio 0·68) with 90% power at 5% significance.
METHODS AND DESIGN:

Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (ISRCTN47823388) is comparing the safety and efficacy of intensive (combined aspirin, clopidogrel, and dipyridamole) vs. guideline antiplatelet therapy, both given for one-month. This international collaborative parallel-group prospective randomized open-label blinded-end-point phase III trial plans to recruit 4100 patients with acute ischemic stroke or transient ischemic attack. Randomization and data collection are performed over a secure Internet site with real-time data validation and concealment of allocation. Outcomes, serious adverse events, and neuroimaging are adjudicated centrally with blinding to treatment allocation.
STUDY OUTCOME:

The primary outcome is stroke recurrence and its severity ('ordinal recurrence' based on modified Rankin Scale) at 90 days, with masked assessment centrally by telephone. Secondary outcomes include vascular events, functional measures (disability, mood, cognition, quality of life), and safety (bleeding, death, serious adverse events).
DISCUSSION:

The trial has recruited more than 50% of its target sample size (latest number: 2399) and is running in 104 sites in 4 countries. One-third of patients presented with a transient ischemic attack.

Citation

Beridze, M., Christensen, H., Dineen, R. A., Duley, L., Heptinstall, S., James, M., …Bath, P. M. (2015). Safety and efficacy of intensive vs. guideline antiplatelet therapy in high-risk patients with recent ischemic stroke or transient ischemic attack: rationale and design of the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial (ISRCTN47823388). International Journal of Stroke, 10(7), https://doi.org/10.1111/ijs.12538

• Journal Article Type: Article
• Acceptance Date: Mar 8, 2015
• Online Publication Date: Jun 16, 2015
• Publication Date: Oct 1, 2015
• Deposit Date: Oct 19, 2016
• Publicly Available Date: Oct 19, 2016
• Journal: International Journal of Stroke
• Print ISSN: 1747-4930
• Electronic ISSN: 1747-4949
• Publisher: SAGE Publications
• Peer Reviewed: Peer Reviewed
• Volume: 10
• Issue: 7
• DOI: https://doi.org/10.1111/ijs.12538
• Keywords: acute stroke, aspirin, clopidogrel, dipyridamole, randomized controlled trial, transient ischemic attack
• Public URL: https://nottingham-repository.worktribe.com/output/981730
• Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/26079743