Clinical trial NCT06763744: Genotype-Guided Abbreviated DAPT Versus Un-Guided De-escalation Therapy in Patients With ACS and HBR
Official title: SMart Angioplasty Research Team- Genotype-Guided Abbreviated DUal AntIplatelet Therapy Versus Un-Guided De-escalation Therapy in Patients With Acute Coronary SyndromE and High Bleeding Risk (SMART-GUIDE-HBR)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI)
High Bleeding Risk
Keywords: CYP2C19 Genotype
Acute coronary syndrome
De-escalation therapy
P2Y12 inhibitor monotherapy
High bleeding risk
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2025-01-08
Enrollment: 3000
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, open-label, two-arm, randomized controlled trial
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Major or clinically relevant non-major bleeding
timeFrame: 6 months after PCI
Secondary outcomes:
measure: Major bleeding
timeFrame: 6 months after PCI
measure: Clinically relevant non-major bleeding
timeFrame: 6 months after PCI
measure: Net adverse clinical event
timeFrame: 6 months after PCI
measure: Major adverse cardiac and cerebrovascular event
timeFrame: 6 months after PCI
measure: All-cause death
timeFrame: 6 months after PCI
measure: Cardiovascular death
timeFrame: 6 months after PCI
measure: MI
timeFrame: 6 months after PCI
measure: Stent thrombosis
timeFrame: 6 months after PCI
measure: Stroke
timeFrame: 6 months after PCI
measure: Repeat revascularization
timeFrame: 6 months after PCI
measure: Target vessel revascularization
timeFrame: 6 months after PCI
measure: Target lesion revascularization
timeFrame: 6 months after PCI
measure: A composite of cardiovascular death, MI, stent thrombosis, or stroke
timeFrame: 6 months after PCI
measure: A composite of cardiovascular death, MI, stent thrombosis, stroke, or repeat revascularization
timeFrame: 6 months after PCI
measure: Total medical cost
timeFrame: 1 year after PCI
measure: Major or clinically relevant non-major bleeding
timeFrame: 1 year after PCI
measure: Major bleeding
timeFrame: 1 year after PCI
measure: Clinically relevant non-major bleeding
timeFrame: 1 year after PCI
measure: Net adverse clinical event
timeFrame: 1 year after PCI
measure: Major adverse cardiac and cerebrovascular event
timeFrame: 1 year after PCI
measure: All-cause death
timeFrame: 1 year after PCI
measure: Cardiovascular death
timeFrame: 1 year after PCI
measure: MI
timeFrame: 1 year after PCI
measure: Stent thrombosis
timeFrame: 1 year after PCI
measure: Stroke
timeFrame: 1 year after PCI
measure: Repeat revascularization
timeFrame: 1 year after PCI
measure: Target vessel revascularization
timeFrame: 1 year after PCI
measure: Target lesion revascularization
timeFrame: 1 year after PCI
measure: A composite of cardiovascular death, MI, stent thrombosis, or stroke
timeFrame: 1 year after PCI
measure: A composite of cardiovascular death, MI, stent thrombosis, stroke, or repeat revascularization
timeFrame: 1 year after PCI
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Samsung Medical Center
name: Joo-Yong Hahn, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: