Clinical trial NCT05657041: Body Weight Adjusted Clopidogrel Treatment in Patients With CORonary Artery Disease
Official title: Body Weight Adjusted Clopidogrel Treatment in Patients With Coronary Artery Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Coronary Artery Disease
Platelet Reactivity
Keywords: Antithrombotic Drugs
Pharmacodynamics
Clopidogrel
Lead sponsor: St. Antonius Hospital
Sponsor class: OTHER
Collaborators: name: St. Antonius hospital Onderzoeksfonds
name: Ace pharmaceuticals
name: Allgen pharmaceuticals
First posted: 2022-12-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, experimental study
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Platelet reactivity
timeFrame: Baseline and 10 days after dose alteration
measure: High on-treatment platelet reactivity (HTPR)
timeFrame: Baseline
measure: High on-treatment platelet reactivity (HTPR)
timeFrame: 10 days
measure: High on-treatment platelet reactivity (HTPR)
timeFrame: 20 days
Secondary outcomes:
measure: Bleeding complications
timeFrame: 30 days
measure: Myocardial infarction
timeFrame: 30 days
measure: Stroke
timeFrame: 30 days
measure: Stent thrombosis
timeFrame: 30 days
measure: All-cause death
timeFrame: 30 days
Other outcomes:
Locations:
city: Nieuwegein
country: Netherlands
facility: StAntoniusH
state: Utrecht
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
Study officials:
References: