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

May 31, 2023 updated by: Jurriën M. ten Berg, MD, PhD, St. Antonius Hospital

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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Utrecht
      • Nieuwegein, Utrecht, Netherlands, 3435CM
        • Not yet recruiting
        • StAntoniusH
        • Contact:
        • Principal Investigator:
          • Jur ten Berg, MD, PhD
        • Sub-Investigator:
          • Wout van den Broek, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Platelet reactivity
Time Frame: Baseline and 10 days after dose alteration
Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow
Baseline and 10 days after dose alteration
High on-treatment platelet reactivity (HTPR)
Time Frame: Baseline
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
Baseline
High on-treatment platelet reactivity (HTPR)
Time Frame: 10 days
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
10 days
High on-treatment platelet reactivity (HTPR)
Time Frame: 20 days
umber of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
20 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Bleeding complications
Time Frame: 30 days
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
Time Frame: 30 days
Number of participants with myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction
30 days
Stroke
Time Frame: 30 days
Number of participants with stroke as defined by VARC definitions
30 days
Stent thrombosis
Time Frame: 30 days
Number of participants with stent thrombosis as defined by ARC
30 days
All-cause death
Time Frame: 30 days
Number of participants with all-cause death as defined by ARC
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
St. Antonius Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
St. Antonius hospital Onderzoeksfonds
Ace pharmaceuticals
Allgen pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 26, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 18, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 20, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 2, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 31, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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