Genotype-Guided Abbreviated DAPT Versus Un-Guided De-escalation Therapy in Patients With ACS and HBR

NCT ID: NCT06763744

Last Updated: 2025-05-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 3000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2029-12-31

Brief Summary

The aim of this study is to assess the safety and efficacy of the CYP2C19 genotype-guided abbreviated dual antiplatelet therapy (DAPT) strategy versus the un-guided stepwise intensity de-escalation of DAPT strategy in patients with acute coronary syndrome (ACS) and high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI).

Detailed Description

Current guidelines recommend reducing the duration of dual antiplatelet therapy (abbreviated DAPT) or de-escalating P2Y12 inhibitor intensity (de-escalation therapy) in patients at risk of major bleeding, even in patients with acute coronary syndromes. A network meta-analysis that indirectly compared these two strategies found that abbreviated dual antiplatelet therapy reduced major bleeding compared with de-escalated dual antiplatelet therapy.

Unlike prasugrel and ticagrelor, which are potent P2Y12 inhibitors, clopidogrel is activated in the liver via the cytochrome P450 2C19 (CYP2C19) metabolic pathway to exert its antiplatelet effects. Its use as monotherapy requires caution, given that CYP2C19 genotypes that may be resistant to clopidogrel are more prevalent in Asian populations than in Western populations.

Therefore, this study aimed to compare the clinical outcomes and confirm the efficacy and safety of an abbreviated dual antiplatelet therapy (Abbreviated DAPT, P2Y12 inhibitor monotherapy) strategy based on CYP2C19 genetic testing and a step-down DAPT strategy (De-escalation therapy) after 1 month of maintenance potent P2Y12 inhibitor-based dual antiplatelet therapy in patients at HBR who underwent PCI for ACS.

Conditions

Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI); High Bleeding Risk

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Genotype-guided abbreviated DAPT

Rapid (CYP2C19\*1/\*17 or \*17/\*17) or normal metabolizers (CYP2C19\*1/\*1) for clopidogrel will receive clopidogrel monotherapy and intermediate or poor metabolizers will receive potent P2Y12 inhibitor (prasugrel or ticagrelor) monotherapy (patients carrying a CYP2C19\*2 or \*3 alleles) after 1 month of potent P2Y12 inhibitor based DAPT.

Group Type: ACTIVE_COMPARATOR

P2Y12 antagonist monotherapy

Intervention Type: DRUG

CYP2C19 genetic testing is performed before discharge after stent insertion. Depending on the test results, rapid (CYP2C19\*1/\*17 or \*17/\*17) or normal (CYP2C19\*1/\*1) metabolizers are treated with clopidogrel monotherapy, and intermediate or poor metabolizers (with CYP2C19\*2 or \*3 alleles) are treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) monotherapy.

Un-guided de-escalation of DAPT

A potent P2Y12 inhibitor is changed to clopidogrel 1 month after PCI, and aspirin is maintained.

Group Type: ACTIVE_COMPARATOR

clopidogrel + aspirin

Intervention Type: DRUG

In this group, a potent P2Y12 inhibitor was changed to clopidogrel (un-guided) 1 month after PCI with maintenance of co-prescription of aspirin (DAPT).

Interventions

P2Y12 antagonist monotherapy

CYP2C19 genetic testing is performed before discharge after stent insertion. Depending on the test results, rapid (CYP2C19\*1/\*17 or \*17/\*17) or normal (CYP2C19\*1/\*1) metabolizers are treated with clopidogrel monotherapy, and intermediate or poor metabolizers (with CYP2C19\*2 or \*3 alleles) are treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) monotherapy.

Intervention Type: DRUG

clopidogrel + aspirin

In this group, a potent P2Y12 inhibitor was changed to clopidogrel (un-guided) 1 month after PCI with maintenance of co-prescription of aspirin (DAPT).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients must be at least 19 years of age
• Patients who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.
• Patients presenting with ACS (ST-elevation myocardial infarction [STEMI] or non-ST-elevation [NSTE] ACS).
• Patients with at least one lesion with equal or greater than 50% diameter stenosis requiring treatment with drug-eluting stents in native coronary artery or graft.
• Patients with high bleeding risk (by ARC-HBR definition or PRECISE-DAPT score 25 or more)

Exclusion Criteria

• Patients unable to provide consent.
• Patients who need chronic anti-coagulation therapy.
• Patients suffering from cardiogenic shock or cardiac arrest
• Patients with known intolerance to aspirin, all P2Y12 inhibitors, or components of drug-eluting stents.
• Clinically significant out of range values for platelet count (< 50,000/mm3) or hemoglobin (<8 g/dL) at screening
• Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
• Pregnant or lactating women.

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Joo-Yong Hahn

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joo-Yong Hahn, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

Samsung Medical Center

Seoul, , South Korea

Countries

South Korea

Central Contacts

Joo-Yong Hahn, MD, PhD

Role: CONTACT

jyhahn@skku.edu

82-2-3410-3419

Ki Hong Choi, MD, PhD

Role: CONTACT

cardiokh@gmail.com

82-2-3410-6653

Facility Contacts

Joo-Yong Hahn, MD, PhD

Role: primary

jyhahn@skku.edu

82-2-3410-3419

Ki Hong Choi

Role: backup

cardiokh@gmail.com

82-2-3410-6653

Other Identifiers

GUIDE-HBR

Identifier Type: -

Identifier Source: org_study_id