POPular GUILTY PILOT: Genotype-guided Clopidogrel Monothe... | NCT05926271

Studies
POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy

NCT05926271

Sponsor

St. Antonius Hospital

Status

Recruiting

Last Update Posted

Dec 3, 2024Actual

Enrollment

200Estimated

Phase

Phase 2

Conditions

Acute Coronary Syndrome
CYP2C19 Polymorphism

Interventions

Clopidogrel

Countries

Netherlands

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Nov 2024

Overall Recruitment Status or Expanded Access Status

Recruiting

Last Known Status

Not provided

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Jul 15, 2023Actual

Primary Completion Date

Jun 15, 2026Estimated

Completion Date

Jan 15, 2027Estimated

First Submitted Date

Jun 7, 2023

First Submission Date that Met QC Criteria

Jun 27, 2023

First Posted Date

Jul 3, 2023Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Nov 28, 2024

Last Update Posted Date

Dec 3, 2024Actual

Description Module

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.

Design Module

Study Type

Interventional

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Not provided

Target Follow-Up Duration

Not provided

Phases

Phase 2

Interventional Study Design

Allocation

Biospecimen

No data available

No data is available for this block.

Enrollment

200Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
Clopidogrel	Drug	See arm description earlier.	Genotype guided arm

Outcomes Module

Primary Outcomes

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 Outcomes

Measure	Description	Time Frame
Mortality	all-cause mortality	3 and 6 months
Myocardial infarction	Myocardial infarction	3 and 6 months

Other Outcomes

Not provided

Eligibility Module

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

Accepts Healthy Volunteers

Yes

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

18 Years

Maximum Age

Not provided

Standard Ages

AdultOlder Adult

Study Population

Not provided

Sampling Method

Not provided

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
Jaouad Azzahhafi, MD	Contact	+31883201321		j.azzahhafi@antoniusziekenhuis.nl
Jurrien ten Berg, MD PhD	Contact	+31883201321		j.ten.berg@antoniusziekenhuis.nl

Overall Officials

Name	Affiliation	Role
Ashley Verburg, MD	St. Antonius Hospital	Study Director

Locations

Facility	Status	City	State	ZIP	Country	Contacts
St. Antonius Hospital	Recruiting	Nieuwegein	Utrecht		Netherlands

ID	Term
D054058	Acute Coronary Syndrome

ID	Term
D017202	Myocardial Ischemia
D006331	Heart Diseases
D002318	Cardiovascular Diseases
D014652	Vascular Diseases

ID	Term
D000077144	Clopidogrel

ID	Term
D013988	Ticlopidine
D058924	Thienopyridines
D013876	Thiophenes
D013457	Sulfur Compounds

Intervention 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.