Highest Efficacy of Dual Antiplatelet Therapy After Carotid Artery Stenting in High Bleeding Risk Patients
brief summary
The optimal duration of dual antiplatelet therapy (DAPT) after carotid artery stenting (CAS) in patients at high bleeding risk (HBR) has not been established in randomized controlled trials. Current practice largely extrapolates from percutaneous coronary intervention (PCI) trials, but anatomical and procedural differences between coronary and carotid arteries limit the validity of this approach. The CHET trial is a multicenter, randomized, open-label, superiority trial designed to compare two DAPT durations after CAS in patients at HBR. After CAS, all eligible patients receive aspirin (100 mg daily) and clopidogrel (75 mg daily) for a 30-day enrichment period. Patients who remain free of net clinical events at day 30 are randomized 1:1 to either single antiplatelet therapy (SAPT; aspirin 100 mg or clopidogrel 75 mg daily, at the treating physician's discretion) for 11 months, or continued DAPT for 11 months. The primary hypothesis is that abbreviated DAPT followed by SAPT is superior to prolonged DAPT in reducing clinically significant bleeding (Bleeding Academic Research Consortium \[BARC\] type 2, 3, or 5) from 30 days to 12 months after CAS, while maintaining noninferiority in net clinical outcomes (composite of nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and major bleeding \[BARC type 3 or 5\]). A total of 1,556 participants (778 per group) will be enrolled across multiple comprehensive stroke centers in the Republic of Korea. Patients will be followed at 5 and 11 months after randomization, with subsequent annual follow-up (in-person or by telephone) until study completion to capture long-term clinical events.
detailed description
1. Study Design CHET is a prospective, multicenter, randomized, open-label, superiority trial conducted at comprehensive stroke centers in the Republic of Korea. Endpoint adjudication is performed by an independent Clinical Event Assessment Committee (CEAC) blinded to treatment allocation, and safety is overseen by an independent Data Safety Monitoring Board (DSMB). 2. Randomization Patients who complete the 30-day enrichment period without a net clinical event are randomized 1:1 via a centralized, secure web-based system using permuted blocks of variable size, stratified by participating center. The allocation sequence and block sizes are concealed from investigators to maintain allocation concealment. 3. Treatment Arms (11 months following randomization) Experimental arm (SAPT): Single antiplatelet therapy with either aspirin 100 mg once daily or clopidogrel 75 mg once daily, at the treating physician's discretion, for 11 months.
Active comparator arm (DAPT): Continued dual antiplatelet therapy with aspirin 100 mg once daily and clopidogrel 75 mg once daily for 11 months. 4. Follow-up Scheduled outpatient visits are performed at 5 months and 11 months after randomization (corresponding to approximately 6 and 12 months after CAS). Following the 11-month visit, participants are followed annually through outpatient visits or telephone contact until study completion in December 2029 to capture long-term clinical events. Antiplatelet therapy after the randomized 11-month treatment period is at the discretion of the treating physician and is not mandated by the protocol. 5. Endpoints 1) Primary safety endpoint: Clinically significant bleeding (BARC type 2, 3, or 5) occurring from 30 days to 12 months after CAS.
2\) Key secondary efficacy endpoint: Net clinical outcome, defined as the composite of nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and major bleeding (BARC type 3 or 5), occurring from 30 days to 12 months after CAS, evaluated under a noninferiority hypothesis (margin 5%, one-sided alpha 2.5%).
official title
Clinical Trial to Obtain the Highest Efficacy of Dual Antiplatelet Therapy After Carotid Artery Stenting in High Bleeding Risk Patients