POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy (POPular GUILTY)

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Coronary Syndrome; CYP2C19 Polymorphism
• Intervention / Treatment: Drug: Clopidogrel

Detailed Description

Rationale: Dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitor is the cornerstone of treatment in patients receiving coronary stent implantation, reducing the risk of stent thrombosis (ST), myocardial infarction (MI) and stroke. However, the need for aspirin is currently challenged as both technical and pharmaceutical advancements reduced atherothrombotic complications such as ST and MI after percutaneous coronary intervention (PCI) and DAPT is associated with bleeding complications. Single antiplatelet therapy (SAPT) after a 1-3 month period of DAPT demonstrated fewer bleeding complications with a similar level of ischemic complications. In addition, potent P2Y12 inhibitor monotherapy was deemed safe without any ST in a pilot study and is currently being investigated in a randomized controlled clinical trial. Since clopidogrel is equally effective in prevention of ischemic complications to ticagrelor and prasugrel in CYP2C19 extensive or ultra-rapid metabolizers, while causing less bleeding complications, this pilot study will explore the safety of genotype-guided clopidogrel monotherapy in CYP2C19 extensive or ultra-rapid metabolizers presenting with Non-ST-Segment Elevation Acute Coronary Syndrome (NSTE-ACS) undergoing successful PCI.

Hypothesis:

Genotype-guided clopidogrel monotherapy is safe in regards to bleeding and ischemic endpoints in NSTE-ACS patients undergoing successful PCI.

Objective:

1. To assess ischemic risk (i.e. efficacy) of genotype-guided clopidogrel monotherapy during the first 6 months following successful PCI in NSTE-ACS patients.
2. To assess bleeding risk (i.e. safety) of genotype-guided clopidogrel monotherapy during the first 6 months following successful PCI in NSTE-ACS patients.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jaouad Azzahhafi, MD; Phone Number: +31883201321; Email: j.azzahhafi@antoniusziekenhuis.nl
• Study Contact Backup: Name: Jurrien ten Berg, MD PhD; Phone Number: +31883201321; Email: j.ten.berg@antoniusziekenhuis.nl

Study Locations

• Netherlands
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands
      • Recruiting
      • St. Antonius Hospital
      • Contact: Prof. J.M. ten Berg, MD, PhD, MSc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Patients aged 18 years or older are eligible for inclusion if all of the following criteria are met:

• 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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Genotype guided arm; 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; See arm description earlier.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	all-cause mortality	3 and 6 months
Myocardial infarction	Myocardial infarction	3 and 6 months
Stent thrombosis	Probable and definite Stent Thrombosis	3 and 6 months
Ischemic stroke	ischemic stroke	3 and 6 months
Major bleeding	BARC 3 or 5 bleeding	3 and 6 months
Major bleeding	BARC 3 bleeding	3 and 6 months
Clinically relevant non-major bleeding	BARC 2 bleeding	3 and 6 months

Collaborators and Investigators

• Sponsor: St. Antonius Hospital
• Investigators: Study Director: Ashley Verburg, MD, St. Antonius Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2023
• Primary Completion (Estimated): June 15, 2026
• Study Completion (Estimated): January 15, 2027

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): December 3, 2024
• Last Update Submitted That Met QC Criteria: November 28, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; Monotherapy; P2Y12 inhibitor; Aspirin free strategy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Myocardial Ischemia; Acute Coronary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel
• Other Study ID Numbers: NL82555.100.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No