Body Weight Adjusted Clopidogrel Treatment in Patients With CORonary Artery Disease (BW-ACCORD)

Body Weight Adjusted Clopidogrel Treatment in Patients With Coronary Artery Disease

Extreme body weights (BW) or body mass index (BMI) affect the pharmacokinetics of antithrombotic drugs and consequently may affect cardiovascular risk during treatment. The goal of this clinical trial is to establish if clopidogrel treatment can be optimized in patients with a low or high BW compared to patients with a normal BW by adjusting the dosage of clopidogrel and evaluating platelet reactivity.

Participants are stratified into three groups based on their BW (Low BW: BW <60kg; normal BW: 60-100kg; High BW: >100 kg)

Clopidogrel dosage will then be adjusted to the BW, as follows:

• Low BW: >10 days clopidogrel 50mg 1dd1, followed by >10 days clopidogrel 25mg 1dd1.
• Normal BW: Clopidogrel 75mg 1dd1.
• High BW: >10 days clopidogrel 150mg 1dd1 followed by >10 days prasugrel 10mg 1dd1.

The primary endpoint of the study is P2Y12 Reaction Units (PRU) and platelet inhibition measured using the VerifyNow measured before starting new treatment regimen (at the end of 10 days of treatment).

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease; Platelet Reactivity
• Intervention / Treatment: Drug: Clopidogrel

Detailed Description

Patients with a high BMI/BW have a higher cardiovascular risk and patients with a low BMI/BW seem to have a higher bleeding risk. A high BMI/BW affects the efficacy of clopidogrel. It is not yet known if this clopidogrel efficacy is altered in patients with a low BMI/BW and whether BW-adjusted treatment can optimise this efficacy. We hypothesize that a personalised treatment will eventually lead to a more optimal effect of clopidogrel, optimizing the balance between bleeding and thrombotic risk. This could benefit therapy compliance.

Primary Objective:

To determine if clopidogrel treatment can be optimized in patients with a low or high BW compared to patients with a normal BW by adjusting the dosage of clopidogrel and evaluating platelet reactivity measured using the VerifyNow.

Secondary Objective(s):

To determine if the CYP2C19 genotype has additional effect on the platelet reactivity in the different treatment groups.

This is a non-randomized single centre, prospective, experimental study in patients with CCS treated with clopidogrel 75mg (and aspirin). This study is designed to be pragmatic and is intended to be hypothesis generating. Patients have to be treated with clopidogrel for at least one month without the occurrence of a major bleeding event, an ischemic event (stroke, myocardial infarction, or coronary revascularization) and have to be free of angina complaints.

Participants are stratified into three groups based on their BW (Low BW: BW <60kg; normal BW: 60-100kg; High BW: >100 kg)

Clopidogrel dosage will then be adjusted to the BW, as follows:

• Low BW: >10 days clopidogrel 50mg 1dd1, followed by >10 days clopidogrel 25mg 1dd1.
• Normal BW: Clopidogrel 75mg 1dd1.
• High BW: >10 days clopidogrel 150mg 1dd1 followed by >10 days prasugrel 10mg 1dd1.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Nieuwegein, Netherlands
    • Recruiting
    • St. Antonius Hospital
    • Contact: Jurrien ten berg; Phone Number: 088 320 09 00; Email: j.ten.berg@antoniusziekenhuis.nl
  • Utrecht
    • Nieuwegein, Utrecht, Netherlands, 3435CM
      • Not yet recruiting
      • StAntoniusH
      • Contact: Wout van den Broek, MD; Phone Number: 088 320 13 37; Email: w.van.den.broek2@antoniusziekenhuis.nl
      • Principal Investigator: Jur ten Berg, MD, PhD
      • Sub-Investigator: Wout van den Broek, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients, male or female, ≥18 years of age
• Patients treated for CCS with clopidogrel 75mg QD (aspirin 100mg QD).
• Patients must be treated with clopidogrel 75mg for at least one month
• Patients must give consent by means of a signed informed consent

Exclusion Criteria:

• Contra-indication for aspirin
• Contra-indication for clopidogrel or prasugrel
• Occurrence of an ischemic event after PCI or ACS (stroke, myocardial infarction, or coronary revascularization)
• Presence of unstable angina complaints.
• Presence of two CYP2C19 Loss-of-function (LOF) alleles (*2 or *3)
• Scheduled for cardiac valve surgery
• Indication for chronic oral anticoagulants
• Expected life span of less than one year
• Pregnancy
• Suboptimal stent placement as determined by the cardiologist.
• Patients at increased risk of bleeding with two of the following characteristics: liver cirrhosis with portal hypertension, enhanced bleeding tendency, active malignancy in the past 12 months, thrombocytopenia, major surgery in the past month, spontaneous intracerebral haemorrhage, traumatic intracerebral haemorrhage in the past 12 months, major bleeding requiring hospitalisation or blood transfusion in the past month, ischaemic CVA in the past 5 months.
• Known with established stent thrombosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: body weight <60kg; Treatment with clopidogrel 50mg once daily for a minimum of 10 days (max. 14 days), followed by a minimum of 10 days treatment with clopidogrel 25mg once daily (max 14 days).	Drug: Clopidogrel; Body weight adjusted clopidogrel dosing; Other Names: Prasugrel; Body weight adjusted
No Intervention: Group 2: body weight 60-100kg; Treatment with clopidogrel 75mg once daily
Experimental: Group 3: body weight >100kg; Treatment with clopidogrel 150mg once daily for a minimum of 10 days (max. 14 days), followed by a minimum of 10 days treatment with prasugrel 10mg once daily (max 14 days).	Drug: Clopidogrel; Body weight adjusted clopidogrel dosing; Other Names: Prasugrel; Body weight adjusted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow	Baseline and 10 days after dose alteration
High on-treatment platelet reactivity (HTPR)	Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208	Baseline
High on-treatment platelet reactivity (HTPR)	Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208	10 days
High on-treatment platelet reactivity (HTPR)	umber of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208	20 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bleeding complications	Number of participants with major or clinically relevant bleeding complications according to the Bleeding Academic Research Consortium Definition for Bleeding (BARC) classification.	30 days
Myocardial infarction	Number of participants with myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction	30 days
Stroke	Number of participants with stroke as defined by VARC definitions	30 days
Stent thrombosis	Number of participants with stent thrombosis as defined by ARC	30 days
All-cause death	Number of participants with all-cause death as defined by ARC	30 days

Collaborators and Investigators

• Sponsor: St. Antonius Hospital
• Collaborators: St. Antonius hospital Onderzoeksfonds; Ace pharmaceuticals; Allgen pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: December 9, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 31, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacodynamics; Clopidogrel; Antithrombotic Drugs
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Body Weight; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: NL81095.100.22

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