Clopidogrel Response and CYP2C19 Genotype in Ischemic Stroke Patients
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Zealand University Hospital
- Enrollment
- 103
- Locations
- 1
- Primary Endpoint
- Number of patients who has clopidogrel HTPR
Study Overview
Brief Summary
Personalized therapy as prophylaxis in ischemic stroke patients is not yet an option. From patients with ischemic heart disease, we know that patients with in vitro high on treatment platelet reactivity (HTPR) have an increased risk of stent thrombosis following per-cutaneous coronary intervention. Other studies have shown association of CYP2C19 genotypes with different responses to the anti platelet drug Clopidogrel. We measure HTPR in ischemic stroke patients on increasing doses of clopidogrel and investigate the CYP2C19 genotype for each patient.
Detailed Description
Background: Clopidogrel (CLO) is a pro-drug metabolized in the liver by the Cytochrom-P450 system to its active component. Studies in acute ischemic stroke (IS) patients have proven that genetic differences in coding of an enzyme responsible for the metabolism of CLO (CYP2C19) results in different response to CLO when tested in the blood. An American study in cardiac patients have shown an association between the genotype and the CLO-response to different dosages of CLO, meaning that patients who are non-responders to low dosages of CLO may be responders to higher CLO dosages. Furthermore, the study showed that patients with a distinct genotype does not gain CLO response even at high CLO dosages (300 mg/day).
Perspective: The study will have an impact on the patient, the relatives and the social economy. The project answers if it is possible to give personalized therapy to IS patients securing the best possible prophylactic treatment for each single patient. Hereby reducing the risk of early death, disability and dependency. The project determines the genetic distribution of CYP2C19 alleles in the Danish IS population and determine the association between genotype and CLO-response in clinically relevant dosages in a Caucasian population of IS patients.
Objective: To determine the correlation between genotype and Clopidogrel response to different CLO dosage and to determine the distribution of different alleles of CYP2C19 genotypes in a Danish IS population.
Hypothesis: CLO response is determined by CYP2C19 genotype, and there is a correlation between drug-response and CYP2C19 genotype.
Method: Systematic recording of data on 103 IS patients receiving prophylactic treatment with CLO 75 mg/day.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Ischemic stroke diagnosis
- •treatment with clopidogrel 75 mg/day
Exclusion Criteria
- •increased risk of bleeding
- •treatment with NOAC, vitamin K antagonist or other antiplatelet drug than clopidogrel
- •unable to give informed consent
Arms & Interventions
Clopidogrel non-responders
Increasing doses og Clopidogrel depending on PRU values measured on VerifyNow
Intervention: Clopidogrel (Drug)
Outcomes
Primary Outcomes
Number of patients who has clopidogrel HTPR
Time Frame: 7 days
Clopidogrel responder status measured with VerifyNow
Number of patients who are carriers of CYP2C19 loss-of-function alleles
Time Frame: 1 day
Genotyping patients for different loss-of-function CYP2C19 alleeles (\*2, \*3)
Number of patients who are carriers of P2Y12-receptor loss-of-function alleles
Time Frame: 1 day
genotyping patients for different loss-of-function P2Y12 receptor alleeles
Secondary Outcomes
No secondary outcomes reported