Pharmacodynamic Outcomes in CCS Patients Treated With an Individualized Treatment Strategy

NCT05773989 | Unknown Phase 4

• 1 other identifier: 2023-504078-39
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with Chronic Coronary Syndrome (CCS) undergoing with elective percutaneous coronary intervention (PCI) are treated with dual antiplatelet therapy (DAPT), consisting of aspirin combined with clopidogrel for 6 months. The aim of DAPT is to prevent recurrent thrombotic events, i.e. death, stent thrombosis and/ or myocardial infarction (MI). However, the trade-off of thrombotic prevention by DAPT is an increased risk of bleeding. Multiple strategies to reduce bleeding risk and optimize outcomes have been proposed. On one hand the bleeding risk can be reduced by shortening the duration of DAPT and omitting aspirin. This has been proven effective in patients with acute coronary syndromes (ACS) compared to standard DAPT, without a significant difference in thrombotic events. On the other hand, personalized medicine by means of genotyping to ensure that a patient is treated with an, for them, effective drug, can be a strategy to optimize patients outcomes. In CCS patients the preferred P2Y12-inhibitor is clopidogrel. However, clopidogrel must first be activated by the CYP2C19 enzyme in the liver. Only then can clopidogrel inhibit the P2Y12-receptor and prevent platelet activation. Almost thirty percent of patients has a genetic variation of the gene encoding this CYP2C19 enzyme. In these patients, clopidogrel is not or hardly activated, putting them at a higher risk of thrombotic events than patients who do not have this gene variation. By determining the CYP2C19 genotype, it is possible to estimate whether clopidogrel will be effective or not. In this trial the investigators evaluate the pharmacodynamic effects of genotype guided P2Y12-inhibitor monotherapy in patients with CCS undergoing PCI. In the intervention arm the CYP2C19 genotype will be assessed using a point-of-care test device on the cardiology ward, which can be performed by (research) nurses. Patients with a CYP2C19 loss-of-function (LOF) allel will be treated with monotherapy ticagrelor or prasugrel. Patients who are non-carrier of a LOF allel will receive clopidogrel. The control arm will be treated with the current standard-of-care, which is DAPT, consisting of aspirin combined with clopidogrel for 6 months. The main goals is to assess the antithrombotic effects of individualized P2Y12 monotherapy strategy versus clopidogrel plus aspirin in elective PCI patients.

Conditions

Coronary Artery Disease; Platelet Reactivity

Keywords

Percutaneous Coronary Intervention; Antithrombotic therapy; CYP2C19; CYP2C19 guided treatment; Pharmacodynamics

Outcome Measures

Primary Outcomes (2)

• Platelet reactivity

  Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow

  Baseline and 30 days after PCI

• High on-treatment platelet reactivity (HTPR)

  Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU \>208

  30 days

Secondary Outcomes (6)

• Bleeding complications

  6 months

• Myocardial infarction

  6 months

• Stroke

  6 months

• Stent thrombosis

  6 months

• All-cause death

  6 months

Study Arms (2)

Genotype guided P2Y12 monotherapy

EXPERIMENTAL

Patients will be tested for the CYP2C19 genotype. Patients without a loss-of-function (LOF) allele will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months.

Drug: CYP2C19 genotype guided P2Y12 monotherapy

Standard DAPT

ACTIVE COMPARATOR

Patients will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months.

Drug: Clopidogrel

Interventions

CYP2C19 genotype guided P2Y12 monotherapy DRUG

Patients without a LOF-allel will receive clopidogrel monotherapy (tablet of 75mg once daily) for 6 months. Patients with a LOF-allel will receive ticagrelor (tablet of 90mg twice daily) or prasugrel (tablet of 10mg once daily) for 6 months.

Also known as: Ticagrelor, Prasugrel, Clopidogrel

Genotype guided P2Y12 monotherapy

Clopidogrel DRUG

Standard DAPT according to current guidelines with clopidogrel (tablet of 75mg once daily) for 6 months and acetylsalicylic acid (tablet 80mg one daily) for 6 months.

Also known as: Aspirin

Standard DAPT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 years of age
• Patients with CCS undergoing successful elective PCI
• Patients with written informed consent as approved by the ethics committee

You may not qualify if:

• Contraindication to aspirin, ticagrelor, prasugrel or clopidogrel
• Under the age of 18 years
• Planned cardiac valve surgery
• Need for chronic oral anticoagulation
• PCI when admitted for ACS
• Life expectancy \< 1 year
• Unable or unwilling to provide informed consent
• Pregnancy
• Suboptimal result of stenting as defined by the operator, preferably explained according the complex-PCI criteria
• Treatment with a strong CYP3A4 inhibitor or inducer
• Treatment with a strong CYP2C19 inhibitor or inducer
• History of definite stent thrombosis

Sponsors & Collaborators

• St. Antonius Hospital: lead

Study Sites (1)

St. Antonius Hospital

Nieuwegein, Utrecht, 3435CM, Netherlands

RECRUITING

MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Ticagrelor; Prasugrel Hydrochloride; Clopidogrel; Aspirin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Ticlopidine; Thienopyridines; Pyridines; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Jurriën ten Berg, MD, PhD

  St. Antonius Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wout van den Broek, MD

CONTACT

088 320 1337; w.van.den.broek2@antoniusziekenhuis.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prospective, parallel, randomized trial

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: March 17, 2023
• Study Start: January 23, 2024
• Primary Completion: December 1, 2024
• Study Completion: May 1, 2025
• Last Updated: January 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)