Clinical trial NCT04072705: Clopidogrel Preventive Effect Based on CYP2C19 Genotype in Ischemic Stroke
Official title: A Multicenter Prospective observationaL Study to evAluate the effecT of Clopidogrel on the prEvention of Major vascuLar Events According to the gEnotype of Cytochrome P450 2C19 in Ischemic Stroke paTients; PLATELET Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Ischemic Stroke
Keywords: Pharmacogenetics
Cytochrome P450 2C19
Clopidogrel
Stroke
Lead sponsor: Gangnam Severance Hospital
Sponsor class: OTHER
Collaborators: name: SAMJIN PHARM
First posted: 2019-08-28
Enrollment: 2927
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with acute ischemic stroke who received clopidogrel 75 mg to 300 mg (in the case of loading dose) within 24 hours of symptom onset and who underwent Cytochrome P450 2C19 genotyping test

Brief summary: The hypothesis of this study is that "the poor metabolizer or intermediate metabolizer of the cytochrome P450 2C19 genotype in patients with acute ischemic stroke is associated with increased risk of composite cardiovascular events (recurrent stroke, myocardial infarction, cardiovascular death) compared to those who of extensive metabolizer of the cytochrome P450 2C19 genotype".

Detailed description: Clopidogrel, one of the antiplatelet agents used for secondary prevention in patients with ischemic stroke and coronary artery disease, has been shown to have a superior antiplatelet effect compared to aspirin, and is therefore being administered to many patients with stroke and coronary artery disease. Clopidogrel inhibits platelet-derived ADP receptor, P2Y12, in the liver to produce an anti-platelet effect. It has been suggested that clopidogrel resistance could be occurred from drug-drug interaction via the same pharmacological metabolic pathway. Previous studies reported that the genotypes of Cytochrome P450 2C19, which is involved in the metabolism of clopidogrel in the liver, lead to differences in drug response and recurrence rates of cardiovascular disease. The risk of recurrence of ischemic stroke was reported to be about 4 times higher in patients with a poor metabolizer or intermediate metabolizer genotype of the Cytochrome P450 2C19 genotype compared to the extensive metabolizer genotype. This genotypes of Cytochrome P450 2C19 were also different according to race.

The researches about cytochrome P450 2C19 genotype and clopidogrel resistance have been conducted mainly in patients with coronary artery disease and are not known in stroke patients. Few studies have examined whether the resistance of clopidogrel according to the genotype of cytochrome P450 2C19 in stroke patients is related to the occurrence and/or recurrence of cardiovascular disease. The hypothesis of this study is that "the poor metabolizer or intermediate metabolizer of the cytochrome P450 2C19 genotype in patients with acute ischemic stroke is associated with increased risk of cardiovascular disease and mortality compared to those who of extensive metabolizer of the cytochrome P450 2C19 genotype".

Eligibility criteria: Inclusion Criteria:

1. Ischemic stroke confirmed by brain CT or MRI
2. Patient who received clopidogrel within 72 hours after onset of ischemic stroke
3. Adults over 19 years
4. Patients who agreed to participate in this study within 7 days after ischemic stroke
5. Patients who underwent Cytochrome P450 2C19 genotype test.

Exclusion Criteria:

1. Patients who currently take anticoagulation or is expected to take anticoagulation with 6 months from the screening date
2. Patients who need other antiplatelet drugs except aspirin and clopidogrel
3. Patients who were taking clopidogrel prior to ischemic stroke
4. Patients scheduled for coronary artery stenting, coronary artery bypass surgery, carotid endarterectomy, carotid and cerebral artery stenting
5. Patients with severe comorbidities or active cancer with an estimated life expectancy of less than two years
6. Patients who participated in other drug clinical trials within the past 30 days
7. Patients with high risk source of potential cardiac source of embolism in TOAST classification
8. Patients who are expected to unable to participate or continue the study

Primary outcomes:
measure: composite cardiovascular events
timeFrame: up to 6 months
Secondary outcomes:
measure: cardiovascular events
timeFrame: up to 6 months
measure: cardiovascular events
timeFrame: up to 6 months
measure: cardiovascular events
timeFrame: up to 6 months
measure: cardiovascular events
timeFrame: up to 6 months
measure: early neurological worsening
timeFrame: up to 7 days
measure: Prognosis
timeFrame: 3 months
Other outcomes:
measure: Incidence of major adverse events
timeFrame: Tile frame: participants will be followed at 0, 1, 3, 6 months
Locations:
city: Yongin-si
country: Korea, Republic of
facility: Yongin Severance Hospital
state: Gyeonggi-do
city: Ansan
country: Korea, Republic of
facility: Department of Neurology Korea University Ansan Hospital
city: Anyang
country: Korea, Republic of
facility: Department of Neurology Hallym University Sacred Heart Hospital
city: Busan
country: Korea, Republic of
facility: Department of Neurology Inje University Busan Paik Hospital
city: Busan
country: Korea, Republic of
facility: Department of Neurology Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Department of Neurology Kosin University Gospel Hospital
city: Changwon
country: Korea, Republic of
facility: Department of Neurology Changwon Fatima Hospital
city: Chuncheon
country: Korea, Republic of
facility: Department of Neurology Hallym University Chuncheon Sacred Heart Hospital
city: Chuncheon
country: Korea, Republic of
facility: Department of Neurology Kangwon National University Hospital
city: Daegu
country: Korea, Republic of
facility: Department of Neurology Keimyung University Dongsan Hospital
city: Daegu
country: Korea, Republic of
facility: Department of Neurology Kyungpook National University Hospital
city: Daejeon
country: Korea, Republic of
facility: Department of Neurology Daejeon Eulji Medical Center Eulji University
city: Gimpo-si
country: Korea, Republic of
facility: Department of Neurology Gimpo Woori Hospital
city: Goyang
country: Korea, Republic of
facility: Department of Neurology National Health Insurance Service Ilsan Hospital
city: Goyang
country: Korea, Republic of
facility: Department of Neurology Myongji Hospital
city: Gwangju
country: Korea, Republic of
facility: Department of Neurology Chosun University Hospital
city: Gwangju
country: Korea, Republic of
facility: Department of Neurology Chonnam National University Hospital
city: Hwaseong-si
country: Korea, Republic of
facility: Department of Neurology Hallym University Dongtan Sacred Heart Hospital
city: Iksan
country: Korea, Republic of
facility: Department of Neurology Wonkwang University Hospital
city: Incheon
country: Korea, Republic of
facility: Department of Neurology Gachon University Gil Medical Center
city: Incheon
country: Korea, Republic of
facility: Department of Neurology Inha University Hospital
city: Incheon
country: Korea, Republic of
facility: Department of Neurology Catholic Kwandong University International St.Mary's Hospital
city: Seongnam
country: Korea, Republic of
facility: Department of Neurology Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Inje University Sanggye Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Seoul Medical Center
city: Seoul
country: Korea, Republic of
facility: Department of Neurology KyungHee University Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Severance Hospital, Yonsei University College of Medicine
city: Seoul
country: Korea, Republic of
facility: Department of Neurology National Medical Center
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology KyungHee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Kangdong Sacred Heart Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology, Gangnam Severance Hospital, Yonsei Univ. College of Medicine
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Chung-Ang University Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Ewha Womans University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Department of Neurology Korea University Guro Hospital
Study officials:
affiliation: Gangnam Severance Hospital
name: KyungYul Lee
role: PRINCIPAL_INVESTIGATOR
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