Highest Efficacy of Dual Antiplatelet Therapy After Carotid Artery Stenting in High Bleeding Risk Patients

Official title

Clinical Trial to Obtain the Highest Efficacy of Dual Antiplatelet Therapy After Carotid Artery Stenting in High Bleeding Risk Patients

Overview

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%).

Interventions

• Drug Intervention 1(DAPT): Drug: Aspirin 100mg + Clopidogrel 75mg. Intervention 2(SAPT): Drug: Asprin 100mg or Clopidogrel 75mg
  * Arm A : Single antiplatelet therapy (SAPT) with aspirin or clopidogrel \- 1 month of dual antiplatelet therapy(100mg aspirin q.d. and 75mg clopidogrel q.d.)→ Randomization → 11 months of single antiplatelet therapy (100mg aspirin q.d. or 75mg clopidogrel q.d.) * Arm B : Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel - 1 month of dual antiplatelet therapy(100mg aspirin q.d. and 75mg clopidogrel q.d.) → Randomization → 11 months of dual antiplatelet therapy (100mg aspirin q.d.

Primary outcome measures

• Clinically significant bleeding [Time frame: From 30 days after carotid artery stenting until 12 months]

Secondary outcome measures (1)

• Combined cardiovascular and cerebrovascular accidents [Time frame: From 30 days after carotid artery stenting until 12 months]

Eligibility criteria

Inclusion criteria

• Patients ≥19 years
• Symptomatic patients with carotid artery stenosis\* greater than 50% and asymptomatic patients with carotid artery stenosis\* greater than 70% who are scheduled to undergo or who have undergone carotid artery stenting
• High bleeding risk is defined as a Bleeding Academic Research Consortium type 3 or 5 bleeding risk of ≥4% at 1 year or a risk of an intracranial hemorrhage (ICH) of ≥1% at 1 year, Patients who meet at least one of the criteria for high bleeding risk\*\* below

• The degree of stenosis is determined using the method performed in the North American Symptomatic Carotid Endarterectomy Trial.

• Criteria for high bleeding risk (≥ 1)

• Incidence of non-access site bleeding within 12 months prior to stenting (gastrointestinal tract or hematuria)
• Presence of BARC type 3 or 5 bleeding regardless of the onset time, but the cause has not been completely cured.
• Adults aged ≥75 years
• Thrombocytopenia < 100,000/mm3 (based on the screening test)
• Blood clotting disorders that increase bleeding (Von Willebrand disease, factor VII, VIII, IX, and XI deficiency)
• Patients with anemia defined as hemoglobin <12g/dL in men and <11g/dL in women or patients who donated blood within 4 weeks (based on the screening test)
• Patients received steroids or NSAIDs for ≥4 weeks
• Patients with active malignancy (except for nonmelanoma skin cancer)
• Renal disease (dialysis, transplantation, Estimated Glomerular Filtration Rate < 60ml/min per 1.73m2)
• Liver disease (cirrhosis with portal hypertension)
• Cerebral microbleeds ≥ 5
• Stroke or transient ischemic attacks within 6 months or Transient amaurosis fugax
• Incidence of nontraumatic intracerebral hemorrhage regardless of duration or incidence of traumatic intracerebral hemorrhage within 12 months

Exclusion criteria

• Incidence of net clinical events, including cardiovascular and cerebrovascular accidents or major bleeding events, within 30 days following carotid artery stenting
• Discontinuation of dual antiplatelet therapy within 30 days after carotid stent implantation (However, use of a single antiplatelet therapy within 7 days due to acute infection and trauma is allowed, but dual antiplatelet therapy must be administered at 28 to 30 days after carotid stent implantation)
• Coronary artery stenting or other vascular stenting or vascular recanalization within 1 year (Revascularization surgery that requires CABG(Coronary Artery Bypass Graft) and other dual antiplatelet therapy)
• Aspirin or clopidogrel hypersensitivity
• Pregnant or breastfeeding women (Women of childbearing need to check for pregnancy using urine or blood tests before enrollment, and use appropriate contraception methods during the clinical trial period)
• Patients requiring anticoagulation for ≥12 months
• Patients requiring administration of other antiplatelet therapies
• Patients who are participating in another intervention clinical trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Samsung Medical Center — Seoul

Publications

• Kim HJ, Song TJ, Park MS, Baek JH, Kim YW, Eun MY, Woo HG, Jeong D, Park H, Jung JM, Kim JY, Kim BJ, Kim YD, Park HK, Choi KH, Kim JG, Cho HJ, Joon An S, Lee SY, Lee SJ, Lee SJ, Lee J, Yoo J, Shin DW, Kang HG, Seo JH, Bang OY, Seo WK; CHET Investigators. Design and rationale of the clinical trial to obtain the highest efficacy of dual antiplatelet therapy after carotid artery stenting in high blee PMID 41802529

Identifiers

NCT: NCT06276374 · SMC 2023-12-107

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗