POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy

NCT05926271 | Recruiting Phase 2 DMC

• 1 other identifier: NL82555.100.22
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this pilot clinical trial is to test the safety and effectiveness of genotype-guided clopidogrel monotherapy in patients presenting with Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) who have undergone successful Percutaneous Coronary Intervention (PCI). The main questions it aims to answer are:

• Is genotype-guided clopidogrel monotherapy effective in reducing ischemic risk during the first six months following successful PCI?
• Is genotype-guided clopidogrel monotherapy safe in terms of reducing bleeding risk during the first six months following successful PCI? Participants will be given genotype-guided clopidogrel monotherapy after their successful PCI procedure and will be monitored for any bleeding or ischemic complications over the next six months. Researchers will compare these results to the typical outcomes associated with traditional Dual antiplatelet therapy (DAPT) to see if genotype-guided clopidogrel monotherapy provides similar or improved protection from ischemic events, but with fewer bleeding complications.

Conditions

Acute Coronary Syndrome; CYP2C19 Polymorphism

Keywords

Acute coronary syndrome; Monotherapy; P2Y12 inhibitor; Aspirin free strategy

Outcome Measures

Primary Outcomes (2)

• Primary efficacy endpoint

  A composite endpoint consisting of all-cause mortality, myocardial infarction, probable and definite Stent Thrombosis and ischemic stroke (the first event that occurs will be counted for this composite endpoint)

  6 months

• Primary safety endpoint

  Composite endpint consisting of major or clinically relevant non-major bleeding (BARC type 2, 3 or 5 bleeding)

  6 months

Secondary Outcomes (7)

• Mortality

  3 and 6 months

• Myocardial infarction

  3 and 6 months

• Stent thrombosis

  3 and 6 months

• Ischemic stroke

  3 and 6 months

• Major bleeding

  3 and 6 months

Study Arms (1)

Genotype guided arm

EXPERIMENTAL

In this study arm, patients with Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) who are extensive or ultra-rapid metabolizers as per their CYP2C19 genotype and have undergone successful percutaneous coronary intervention (PCI) will receive a genotype-guided monotherapy. The intervention will be clopidogrel, a potent P2Y12 inhibitor, administered in accordance with the patient's specific genotype. Clopidogrel following PCI will be given with an initial loading dose (300-600mg orally), followed by a maintenance dose of 75mg daily for a defined period, at least 6 months.

Drug: Clopidogrel

Interventions

Clopidogrel DRUG

See arm description earlier.

Genotype guided arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of NSTE-ACS (i.e. NSTEMI or unstable angina)
• Successful PCI (according to the treating physician) with implantation of new generation drug eluting stents.
• CYP2C19 extensive or ultra-rapid metabolizer

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• CYP2C19 poor or intermediate metabolizer
• Known allergy or contraindication for aspirin or clopidogrel.
• Concurrent use of oral anticoagulants (e.g. because of atrial fibrillation)
• Ongoing indication for DAPT at admission (e.g. due to recent PCI or ACS)
• High-risk features for PCI including left main disease, chronic total occlusion, bifurcation lesion requiring 2-stent treatment, saphenous or arterial graft lesion, severely calcified lesion requiring the use of the Rotablator system, ≥3 treated vessels, ≥ 3 stents implanted and total stent length \>60 mm
• Recent stroke, transient ischemic attack (TIA) or intracranial bleeding
• Severe hepatic impairment (Child Pugh class C)
• Planned surgical intervention within 6 months of PCI
• Patients requiring staged procedure (to avoid heterogeneity in the duration of pharmacological treatment between index and staged procedures)
• Pregnant or breastfeeding women at time of enrolment
• Participation in another trial with an investigational drug or device

Sponsors & Collaborators

• St. Antonius Hospital: lead

Study Sites (1)

St. Antonius Hospital

Nieuwegein, Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Acute Coronary Syndrome

Interventions

Clopidogrel

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ashley Verburg, MD

  St. Antonius Hospital

  STUDY DIRECTOR

Central Study Contacts

Jaouad Azzahhafi, MD

CONTACT

+31883201321; j.azzahhafi@antoniusziekenhuis.nl

Jurrien ten Berg, MD PhD

CONTACT

+31883201321; j.ten.berg@antoniusziekenhuis.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. J.M. ten Berg

Model Details: This pilot, genotype-guided clinical trial aims to assess the safety and efficacy of clopidogrel monotherapy in Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) patients post-successful percutaneous coronary intervention (PCI). Participants, identified as extensive or ultra-rapid metabolizers by CYP2C19 genotype, will receive clopidogrel monotherapy. The primary outcomes include the ischemic risk (efficacy) and bleeding risk (safety) during the first six months post-PCI. The trial hypothesizes that genotype-guided clopidogrel monotherapy is safe and efficacious in mitigating bleeding and ischemic complications.

Study Record Dates

• First Submitted: June 7, 2023
• First Posted: July 3, 2023
• Study Start: July 15, 2023
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): January 15, 2027
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)