The Acute S t roke or Transient Isc h emic Attack Treated with Tic a gre l or and Aspirin for Pr e vention of S troke and Death (THALES) trial: Rationale and design

Abstract

Rationale: In patients with acute cerebral ischemia, the rate of stroke, myocardial infarction, or death during 90 days was reported to be non-significantly lower with ticagrelor compared with aspirin, with no increase in major hemorrhage. Dual antiplatelet therapy may be more effective in this setting.

Aim: To investigate whether ticagrelor combined with aspirin are superior to aspirin alone in preventing stroke or death in patients with non-severe, non-cardioembolic ischemic stroke or high-risk transient ischemic attack.

Design: The Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) trial is a randomized, placebo-controlled, double-blind, event-driven study. Patients will be randomized within 24 h of onset of acute ischemic symptoms. THALES is expected to randomize 13,000 at ∼450 sites worldwide, to collect 764 primary outcome events. Study treatments are ticagrelor 180 mg loading dose on day 1, then 90 mg twice daily on days 2-30, or matching placebo. All patients will also receive open-label aspirin 300-325 mg on day 1, then 75-100 mg once daily on days 2-30.

Study outcomes: The primary efficacy outcome is time to the composite endpoint of stroke or death through 30-day follow-up. The primary safety outcome is time to first severe bleeding event.

Discussion: The THALES trial will provide important information about the benefits and risks of dual antiplatelet therapy with ticagrelor and aspirin in patients with acute cerebral ischemia in a global setting (funding: AstraZeneca).

Clinical trial registration url: http://www.clinicaltrials.gov . Unique identifier: NCT03354429.

Keywords: Stroke; TIA; antiplatelet; aspirin; cerebral ischemia; ticagrelor.

Figure 1.

THALES study design. R: randomization. Ticagrelor 180 mg loading dose (day 1) then 90 mg twice daily (days 2–30). Aspirin 300–325 mg loading dose (day 1) then 75–100 mg daily (days 2–30).