POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy

Acute Coronary Syndrome Clinical Trial

— POPular GUILTY  

Official title:

POPular GUILTY PILOT: Genotype-guided Clopidogrel Monotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05926271
• Other study ID #: NL82555.100.22
• Status: Recruiting
• Phase: Phase 2
• Start date: July 15, 2023
• Est. completion date: January 15, 2025

Study information

• Verified date: June 2023
• Source: St. Antonius Hospital
• Contact: Jaouad Azzahhafi, MD
• Phone: +31883201321
• Email: j.azzahhafi[@]antoniusziekenhuis.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: January 15, 2025
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• CYP2C19 Polymorphism

Intervention

Drug:
• Clopidogrel
See arm description earlier.

Locations

Country	Name	City	State
Netherlands	St. Antonius Hospital	Nieuwegein	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
St. Antonius Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Primary safety endpoint	Composite endpint consisting of major or clinically relevant non-major bleeding (BARC type 2, 3 or 5 bleeding)	6 months
Secondary	Mortality	all-cause mortality	3 and 6 months
Secondary	Myocardial infarction	Myocardial infarction	3 and 6 months
Secondary	Stent thrombosis	Probable and definite Stent Thrombosis	3 and 6 months
Secondary	Ischemic stroke	ischemic stroke	3 and 6 months
Secondary	Major bleeding	BARC 3 or 5 bleeding	3 and 6 months
Secondary	Major bleeding	BARC 3 bleeding	3 and 6 months
Secondary	Clinically relevant non-major bleeding	BARC 2 bleeding	3 and 6 months