Clopidogrel with aspirin in High-risk patients with Acute Non-disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial

Abstract

Background: In patients with a minor ischaemic stroke or transient ischaemic attack (TIA), separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin (clopidogrel-aspirin) or ticagrelor plus aspirin (ticagrelor-aspirin) are more effective than aspirin alone in stroke secondary prevention. However, these two sets of combination have not been directly compared. Since clopidogrel was less effective in stroke patients who were CYP2C19 loss-of-function (LOF) allele carriers, whether ticagrelor-aspirin is clinically superior to clopidogrel-aspirin in this subgroup of patients with stroke is unclear.

Aim: To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE-2) trial.

Design: CHANCE-2 is a randomised, double-blind, double-dummy, placebo-controlled, multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers: ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily on days 2-90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg daily on days 2-90), plus open-label aspirin with a dose of 75-300 mg on day 1 followed by 75 mg daily on day 2-21. All will be followed for 1 year.

Study outcomes: The primary efficacy outcome is any stroke (ischaemic or haemorrhagic) within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 months.

Discussion: The CHANCE-2 trial will evaluate whether ticagrelor-aspirin is superior to clopidogrel-aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers.

Trial registration number: NCT04078737.

Keywords: stroke.

Figure 1

CHANCE-2 study design. CHANCE-2, Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events; NIHSS, National Institutes of Health Stroke Scale; TIA, transient ischaemic attack；ASA，aspirin; ULN, upper limit of normal; ALT, alanine aminotransferase; AST，aspartate transaminase；AV, atrioventricular.

Figure 2

Summary of inclusion and exclusion criteria. HR-NICE, high-risk patients with acute non-disabling cerebrovascular events (TIA or acute minor stroke); LOF, loss-of-function.