The Association Between Plasma or Platelet microRNAs and Clopidogrel Low Response and Its Mechanism
试验速览
- 阶段
- 4 期
- 入组人数
- 400
- 试验地点
- 1
- 主要终点
- The expressions of miRNAs profile
研究概览
简要总结
Clopidogrel is an important anti-platelet agent.However, about 30% of the coronary artery disease patients presented clopidogrel low response (CLR).Previous studies showed that the cardiovascular event ratio of the CLR patients was 4.4 times of the normal responders.
It is known that the plasma and platelet miRNAs are determined by different disease status when platelets are released from the megakaryocyte, and the platelet miRNAs can adjust the expressions of the platelet's receptors and proteins.The purpose of this study is to find multiple platelet miRNAs involved in the development of CLR, and platelet miRNAs cause CLR through adjusting the expressions of the key receptors and proteins in the ADP activating pathway and consequently reducing their responses to clopidogrel.
The CLR will be detected by light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-P). Differential expressions of plasma and platelet miRNAs profile in CLR patients will be screened by deep sequencing and validated to investigate the association between plasma and platelet miRNAs profile and CLR as well as the patients' prognosis.The study results would serve as markers for individualized anti-platelet treatment, and supply new targets for the treatment of coronary artery disease.
详细描述
A multiphase, case-control study was designed to identify plasma and platelet miRNAs as surrogate markers for CLR .
All patients take 300mg loading dose clopidogrel plus 100mg daily ASA and 75mg daily clopidogrel after admission. Patients are recruited after percutaneous coronary intervention (PCI). Light transmittancy aggregation (LTA) in response to 5μM ADP is to measured 5 days after taking the loading dose clopidogrel.Than CLR patients were selected.
In the initial biomarker-screening stage, plasma and platelet samples from 20 CLR patients and 20 controls underwent Solexa sequencing to identify miRNAs that showed significant differences between the CLR cases and matched controls.
Subsequently,we performed a biomarker confirmation analysis with a hydrolysis probe-based RT-qPCR assay to refine the number of plasma and platelet miRNAs in the CLR signature. This analysis was carried out in 2 phases: (a) the biomarker-selection phase, in which plasma and platelet samples from 20 CLR patients and 20 control individuals formed the training set, and (b) the biomarker-validation phase, in which plasma and platelet samples from an additional 80 CLR patients and 80 controls formed the validation set.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients who receive stent implantation;
- •Patients who take 100mg daily ASA and 75mg daily clopidogrel
- •Patient age >18 years and <80 years old;
- •Signed inform consent
排除标准
- •Allergy or intolerance to ASA,clopidogrel;
- •Patients who are planning to take warfarin or drugs that potentially could interfere with the anti-platelet effects of ASA,clopidogrel.
研究组 & 干预措施
Regular DAPT(IPA≤60%)
ASA and Clopidogrel
干预措施: Clopidogrel (Drug)
Regular DAPT(IPA≤60%)
ASA and Clopidogrel
干预措施: acetylsalicylic acid (ASA) (Drug)
Regular DAPT(IPA>60%)
ASA and Clopidogrel
干预措施: Clopidogrel (Drug)
Regular DAPT(IPA>60%)
ASA and Clopidogrel
干预措施: acetylsalicylic acid (ASA) (Drug)
结局指标
主要结局
The expressions of miRNAs profile
时间窗: 5-days After recruited
Two pools of plasma and platelet were collected from participants separately. The total RNA of each pool was extracted by using Trizol Reagent. An initial screening of miRNAs expression was performed by Solexa sequencing. And differential expression was validated using RT-qPCR in individuals samples.
次要结局
- Clinical efficacy(1-month and 1-year after recruited)
研究者
Chunjian Li
Professor
The First Affiliated Hospital with Nanjing Medical University