Randomized Controlled Trial for Evaluating CYP2C19 Allele Genotype-guided Clopidogrel Treatment Outcomes in Real-world Practice After the ePCI
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 283
- 试验地点
- 5
- 主要终点
- Number of Study Participants Who Died From Any Cause (Death From Any Cause)
研究概览
简要总结
The study purposed to learn how clopidogrel-based antiplatelet treatment for preventing adverse cardiovascular events after ePCI works in chronic coronary artery disease when guided by personal genetic characteristics for drug metabolism.
The study aimed to answer two research questions:
- Does CYP2C19 genotype-guided clopidogrel treatment provide better clinical outcomes when compared with conventional treatment selection led without CYP2C19 genotyping?
- Can CYP2C19 genotype-guided antiplatelet treatment be beneficially applied in real-world clinical practice?
After obtaining the informed consent eligible study participants screened by inclusion and exclusion criteria were randomized and allocated into two groups:
- for whom the CYP2C19 genotype-guided clopidogrel treatment has been applied - the experimental group,
- for whom conventional clopidogrel has been applied without CYP2C19 genotyping - the control group.
The experimental group participants underwent CYP2C19 genotyping. Study participants with CYP2C19 normal function alleles (NFA) *2, *3 genotypes constituted the separate experimental arm and received clopidogrel-based preventive antiplatelet treatment.
Participants with CYP2C19 *2 and *3 loss of function (LoF) alleles were allocated to the separate experimental group and received preventive antiplatelet treatment alternative to clopidogrel.
Study participants who had not undergone CYP2C19 genotyping and received conventional preventive antiplatelet treatment with clopidogrel were assigned as active comparators.
All participants in the experimental and comparator groups underwent standard clinical investigations by current guideline recommendations for:
- the initial assessment,
- follow-up and detection of major adverse cardiovascular events. All patients received the conventional drug treatment by current guideline recommendations for chronic coronary artery disease and comorbid condition management and adverse cardiovascular events prevention.
The main research outcome measures include:
- evaluating clinical outcomes of CYP2C19 genotype-guided antiplatelet treatment application,
- describing models for application of CYP2C19 genotype-guided antiplatelet treatment,
- learning about potential access points to the real practice process pipeline for implementation of genotype-guided medication treatment.
详细描述
The concept of the study is based on current evidence from multiple genetic and clinical studies. At this stage of development preventive treatment of chronic coronary artery disease after ePCI is challenged by risks related to multi-morbidity, recurrent MACCEs and bleeding. Scientific evidence broadly supports pharmacogenetic approaches for routine use of P2Y12 inhibitors (clopidogrel or alternative). Clopidogrel remains the most commonly used P2Y12 inhibitor in the post-ePCI settings. Along with disease-related and co-morbid factors treatment effects are influenced by the variability of the CYP2C19 genotype in the population, which significantly increases the risk of MACCE in loss of function allele (LoF) carriers even with conventional clopidogrel treatment. To improve treatment, a pharmacogenetic expediency model for drug selection is introduced. CYP2C19 allele genotype-guided clopidogrel or an alternative P2Y12 inhibitor treatment is based on robust evidence.
The study aimed to learn the comparative benefits of CYP2C19 genotype-guided versus conventional clopidogrel treatment selection applied in real clinical practice for preventing adverse cardiovascular events after ePCI in chronic coronary artery disease.
For this purpose, the randomized parallel-group controlled study for CYP2C19 genotype-guided clopidogrel treatment outcomes evaluation for chronic coronary artery disease after the ePCI in real-world practice was conducted.
The study addressed research-specific objectives:
- forming and random allocating of participants into study arms for CYP2C19 allele genotype-guided versus conventional clopidogrel treatment,
- ensuring RT-PCR based assay for CYP2C19 *2, *3 LoF alleles detection in randomly selected study participants and forming the experimental study groups,
- characterizing clinical traits of study participants and observing adverse clinical events during the 12-month course of study intervention treatment;
- evaluating the clinical and non-clinical study outcomes. Following the completion of the informed consent, 283 patients eligible for inclusion and exclusion criteria have been enrolled in the study and randomly allocated into two groups.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Outcomes Assessor)
入排标准
- 年龄范围
- 35 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with chronic coronary artery disease;
- •Undergone elective PCI within the last 12 weeks without procedure-related complications;
- •LVEF≥38% after index PCI;
- •Completed informed consent form for participation in the study;
排除标准
- •Concomitant using of potent CYP3A4 or CYP2C19 inhibitors;
- •Morbid obesity, BMI 40 kg/sq.m or more;
- •Type 1 diabetes mellitus;
- •Poorly controlled type 2 diabetes mellitus, HbA1c - 9% or more;
- •Acute Myocardium Infarction;
- •Coronary artery bypass grafting performed within the last 12 weeks;
- •Valvular heart disease due to dysplasia, connective tissue disorders or inflammatory disorders, or valvular disorders requiring cardiac surgery;
- •History of severe hepatic impairment;
- •Severe chronic kidney disease;
- •Clinically important leucopenia, lymphopenia, thrombocytopenia or thrombocytosis;
- •History of hemorrhagic diathesis or coagulopathy;
- •An active or an obvious threat of bleeding (including GI bleeding):
- •Bleeding within the past 6 months that required hospitalization;
- •Blood transfusion during the past 6 months or its refusal;
- •History of intracranial hemorrhage;
- •Cardiac or non-cardiac degenerative disease, including: cardiomyopathy, restrictive lung disease, or Neurodegenerative diseases;
- •Malignant tumor (cancer) that limits life expectancy to less than one year;
- •Current chemotherapy or immunosuppressive therapy;
- •Ongoing immunosuppression or immunosuppressive conditions;
- •Pregnancy or lactation period;
- •Any disease/condition control of which is not achieved;
- •Personal (patient/physician dependent) or health care system-related circumstances that can restrict or limit any study procedures or operations.
结局指标
主要结局
Number of Study Participants Who Died From Any Cause (Death From Any Cause)
时间窗: within a 12-month of the study follow-up
The event of death from any cause reported by the physician according to the WHO Clinical criteria for the determination of death or the incident declared by the caregiver of the patient and checked for appropriateness in hospital registries or the national death registry within the study follow-up period, from the date of study enrollment until the date of the event.
Number of Study Participants Who Died From Any Cardiovascular Cause (Death From Cardiovascular Cause)
时间窗: within a 12-month of the study follow-up
The event of death from any cardiovascular cause reported by the physician according the SCTI (Standardized Data Collection for Cardiovascular Trials Initiative) definitions or the incident declared by the caregiver of the patient and checked for appropriateness in hospital registries or the national death registry within the study follow-up period, from the date of study enrollment until the date of the event.
Number of Study Participants Who Died From Non-cardiovascular Causes (Death From Non-cardiovascular Cause)
时间窗: within a 12-month of the study follow-up
The event of death from a non-cardiovascular cause reported by the physician or the incident declared by the caregiver of the patient and checked for appropriateness in hospital registries or the national death registry within the study follow-up period, from the date of study enrollment until the date of the event.
次要结局
- Number of Study Participants Who Experienced a Stroke or Transitory Cerebral Ischemic Event Within the Study Follow-up Period (Stroke or TIA)(within a 12-month of the study follow-up)
- Number of Study Participants Who Experienced Heart Failure Event (Heart Failure Event)(within a 12-month of the study follow-up)
- Number of Study Participants Who Experienced Major Bleeding (Major Bleeding)(within a 12-month of the study follow-up)
- Number of Study Participants Who Experienced Non-fatal Myocardial Infarction (Non-fatal Myocardial Infarction)(within a 12-month of the study follow-up)
- Number of Study Participants Who Experienced Unstable Angina or Angina Requiring Hospitalization (Unstable Angina)(within a 12-month of the study follow-up)
- Number of Study Participants Who Experienced Non-major Bleeding (Non-major Bleeding)(within a 12-month of the study follow-up)
- Number of Study Participants Who Experienced Percutaneous Coronary Intervention or Coronary Artery Bypass-grafting (Repeated Coronary Revascularization)(within a 12-month of the study follow-up)