Plasma and Platelet microRNAs in Clopidogrel Low Response Patients (PPRC)

February 11, 2016 updated by: Chunjian Li, The First Affiliated Hospital with Nanjing Medical University

The Association Between Plasma or Platelet microRNAs and Clopidogrel Low Response and Its Mechanism

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Chunjian Li, Ph.D
  • Phone Number: 6018 +86-25-83718836
  • Email: lijay@njmu.edu.cn

Study Contact Backup

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Recruiting
        • First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Regular DAPT(IPA≤60%)
ASA and Clopidogrel
Drug: Clopidogrel
(ASA 100mg daily and Clopidogre 75mg daily)* 12 month.
Other Names:
  • Plavix
Drug: acetylsalicylic acid (ASA)
Active Comparator: Regular DAPT(IPA>60%)
ASA and Clopidogrel
Drug: Clopidogrel
(ASA 100mg daily and Clopidogre 75mg daily)* 12 month.
Other Names:
  • Plavix
Drug: acetylsalicylic acid (ASA)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The expressions of miRNAs profile
Time Frame: 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.
5-days After recruited

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical efficacy
Time Frame: 1-month and 1-year after recruited
1-month and 1-year death,non-fatal myocardial infarction,ischemic stroke,revascularization and stent thrombosis(ARC definition)
1-month and 1-year after recruited

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bleeding
Time Frame: 1-month and 1-year after recruited
1-month and 1-year minor,moderate and major bleeding
1-month and 1-year after recruited

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The First Affiliated Hospital with Nanjing Medical University

Collaborators

National Natural Science Foundation of China

Investigators

  • Principal Investigator: Chunjian Li, The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2015

Primary Completion (Anticipated)

December 1, 2016

Study Completion (Anticipated)

December 1, 2016

Study Registration Dates

First Submitted

May 5, 2015

First Submitted That Met QC Criteria

May 18, 2015

First Posted (Estimate)

May 19, 2015

Study Record Updates

Last Update Posted (Estimate)

February 15, 2016

Last Update Submitted That Met QC Criteria

February 11, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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