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

Primary Purpose

Coronary Artery Disease, Platelet Reactivity

Status
Recruiting
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Clopidogrel
Sponsored by
St. Antonius Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Coronary Artery Disease focused on measuring Antithrombotic Drugs, Pharmacodynamics, Clopidogrel

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • StAntoniusH
  • St. Antonius HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

No Intervention

Experimental

Arm Label

Group 1: body weight <60kg

Group 2: body weight 60-100kg

Group 3: body weight >100kg

Arm Description

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).

Treatment with clopidogrel 75mg once daily

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).

Outcomes

Primary Outcome Measures

Platelet reactivity
Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow
High on-treatment platelet reactivity (HTPR)
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
High on-treatment platelet reactivity (HTPR)
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
High on-treatment platelet reactivity (HTPR)
umber of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208

Secondary Outcome Measures

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

Full Information

First Posted
November 18, 2022
Last Updated
May 31, 2023
Sponsor
St. Antonius Hospital
Collaborators
St. Antonius hospital Onderzoeksfonds, Ace pharmaceuticals, Allgen pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05657041
Brief Title
Body Weight Adjusted Clopidogrel Treatment in Patients With CORonary Artery Disease
Acronym
BW-ACCORD
Official Title
Body Weight Adjusted Clopidogrel Treatment in Patients With Coronary Artery Disease
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 26, 2023 (Actual)
Primary Completion Date
August 1, 2024 (Anticipated)
Study Completion Date
November 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
St. Antonius Hospital
Collaborators
St. Antonius hospital Onderzoeksfonds, Ace pharmaceuticals, Allgen pharmaceuticals

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Coronary Artery Disease, Platelet Reactivity
Keywords
Antithrombotic Drugs, Pharmacodynamics, Clopidogrel

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Model Description
prospective, experimental study
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: body weight <60kg
Arm Type
Experimental
Arm Description
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).
Arm Title
Group 2: body weight 60-100kg
Arm Type
No Intervention
Arm Description
Treatment with clopidogrel 75mg once daily
Arm Title
Group 3: body weight >100kg
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Prasugrel, Body weight adjusted
Intervention Description
Body weight adjusted clopidogrel dosing
Primary Outcome Measure Information:
Title
Platelet reactivity
Description
Change in P2Y12 Reaction Units (PRU) measured using the VerifyNow
Time Frame
Baseline and 10 days after dose alteration
Title
High on-treatment platelet reactivity (HTPR)
Description
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
Time Frame
Baseline
Title
High on-treatment platelet reactivity (HTPR)
Description
Number of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
Time Frame
10 days
Title
High on-treatment platelet reactivity (HTPR)
Description
umber of participants with high on-treatment platelet reactivity (HTPR) defined by a PRU >208
Time Frame
20 days
Secondary Outcome Measure Information:
Title
Bleeding complications
Description
Number of participants with major or clinically relevant bleeding complications according to the Bleeding Academic Research Consortium Definition for Bleeding (BARC) classification.
Time Frame
30 days
Title
Myocardial infarction
Description
Number of participants with myocardial infarction as defined by the 4th Universal Definition of Myocardial Infarction
Time Frame
30 days
Title
Stroke
Description
Number of participants with stroke as defined by VARC definitions
Time Frame
30 days
Title
Stent thrombosis
Description
Number of participants with stent thrombosis as defined by ARC
Time Frame
30 days
Title
All-cause death
Description
Number of participants with all-cause death as defined by ARC
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
StAntoniusH
City
Nieuwegein
State/Province
Utrecht
ZIP/Postal Code
3435CM
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wout van den Broek, MD
Phone
088 320 13 37
Email
w.van.den.broek2@antoniusziekenhuis.nl
First Name & Middle Initial & Last Name & Degree
Jur ten Berg, MD, PhD
First Name & Middle Initial & Last Name & Degree
Wout van den Broek, MD
Facility Name
St. Antonius Hospital
City
Nieuwegein
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jurrien ten berg
Phone
088 320 09 00
Email
j.ten.berg@antoniusziekenhuis.nl

12. IPD Sharing Statement

Plan to Share IPD
No

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Body Weight Adjusted Clopidogrel Treatment in Patients With CORonary Artery Disease

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