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

Primary Purpose

Acute Coronary Syndrome, CYP2C19 Polymorphism

Status
Recruiting
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Clopidogrel
Sponsored by
St. Antonius Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Coronary Syndrome focused on measuring Acute coronary syndrome, Monotherapy, P2Y12 inhibitor, Aspirin free strategy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • St. Antonius HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Genotype guided arm

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Mortality
all-cause mortality
Myocardial infarction
Myocardial infarction
Stent thrombosis
Probable and definite Stent Thrombosis
Ischemic stroke
ischemic stroke
Major bleeding
BARC 3 or 5 bleeding
Major bleeding
BARC 3 bleeding
Clinically relevant non-major bleeding
BARC 2 bleeding

Full Information

First Posted
June 7, 2023
Last Updated
June 27, 2023
Sponsor
St. Antonius Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05926271
Brief Title
POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy
Acronym
POPular GUILTY
Official Title
POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 15, 2023 (Anticipated)
Primary Completion Date
June 15, 2024 (Anticipated)
Study Completion Date
January 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Antonius Hospital

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Coronary Syndrome, CYP2C19 Polymorphism
Keywords
Acute coronary syndrome, Monotherapy, P2Y12 inhibitor, Aspirin free strategy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Genotype guided arm
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Intervention Description
See arm description earlier.
Primary Outcome Measure Information:
Title
Primary efficacy endpoint
Description
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)
Time Frame
6 months
Title
Primary safety endpoint
Description
Composite endpint consisting of major or clinically relevant non-major bleeding (BARC type 2, 3 or 5 bleeding)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Mortality
Description
all-cause mortality
Time Frame
3 and 6 months
Title
Myocardial infarction
Description
Myocardial infarction
Time Frame
3 and 6 months
Title
Stent thrombosis
Description
Probable and definite Stent Thrombosis
Time Frame
3 and 6 months
Title
Ischemic stroke
Description
ischemic stroke
Time Frame
3 and 6 months
Title
Major bleeding
Description
BARC 3 or 5 bleeding
Time Frame
3 and 6 months
Title
Major bleeding
Description
BARC 3 bleeding
Time Frame
3 and 6 months
Title
Clinically relevant non-major bleeding
Description
BARC 2 bleeding
Time Frame
3 and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jaouad Azzahhafi, MD
Phone
+31883201321
Email
j.azzahhafi@antoniusziekenhuis.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Jurrien ten Berg, MD PhD
Phone
+31883201321
Email
j.ten.berg@antoniusziekenhuis.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashley Verburg, MD
Organizational Affiliation
St. Antonius Hospital
Official's Role
Study Director
Facility Information:
Facility Name
St. Antonius Hospital
City
Nieuwegein
State/Province
Utrecht
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Prof. J.M. ten Berg, MD, PhD, MSc

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy

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