Clinical trial NCT02447809: Plasma and Platelet microRNAs in Clopidogrel Low Response Patients
Official title: The Association Between Plasma or Platelet microRNAs and Clopidogrel Low Response and Its Mechanism
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: microRNA
Platelet
Clopidogrel low response
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2015-05-19
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: The expressions of miRNAs profile
timeFrame: 5-days After recruited
Secondary outcomes:
measure: Clinical efficacy
timeFrame: 1-month and 1-year after recruited
Other outcomes:
measure: Bleeding
timeFrame: 1-month and 1-year after recruited
Locations:
city: Nanjing
country: China
facility: First Affiliated Hospital of Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Chunjian Li
role: PRINCIPAL_INVESTIGATOR
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