Plasma and Platelet microRNAs in Clopidogrel Low Response Patients
PPRC
The Association Between Plasma or Platelet microRNAs and Clopidogrel Low Response and Its Mechanism
1 other identifier
interventional
400
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4 coronary-artery-disease
Started Jan 2015
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2015
CompletedFirst Submitted
Initial submission to the registry
May 5, 2015
CompletedFirst Posted
Study publicly available on registry
May 19, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2016
CompletedFebruary 15, 2016
February 1, 2016
1.9 years
May 5, 2015
February 11, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
The expressions of miRNAs profile
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 Outcomes (1)
Clinical efficacy
1-month and 1-year after recruited
Other Outcomes (1)
Bleeding
1-month and 1-year after recruited
Study Arms (2)
Regular DAPT(IPA≤60%)
EXPERIMENTALASA and Clopidogrel
Regular DAPT(IPA>60%)
ACTIVE COMPARATORASA and Clopidogrel
Interventions
(ASA 100mg daily and Clopidogre 75mg daily)\* 12 month.
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
First Affiliated Hospital of Nanjing Medical University
Nanjing, Jiangsu, 210029, China
Related Publications (12)
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502. doi: 10.1056/NEJMoa010746.
PMID: 11519503BACKGROUNDSiller-Matula JM, Trenk D, Schror K, Gawaz M, Kristensen SD, Storey RF, Huber K; EPA (European Platelet Academy). Response variability to P2Y12 receptor inhibitors: expectations and reality. JACC Cardiovasc Interv. 2013 Nov;6(11):1111-28. doi: 10.1016/j.jcin.2013.06.011.
PMID: 24262612BACKGROUNDCalin GA, Croce CM. MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 2006 Aug 1;66(15):7390-4. doi: 10.1158/0008-5472.CAN-06-0800.
PMID: 16885332BACKGROUNDHu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, Chen Y, Xu L, Zen K, Zhang C, Shen H. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010 Apr 1;28(10):1721-6. doi: 10.1200/JCO.2009.24.9342. Epub 2010 Mar 1.
PMID: 20194856BACKGROUNDClancy L, Freedman JE. New paradigms in thrombosis: novel mediators and biomarkers platelet RNA transfer. J Thromb Thrombolysis. 2014 Jan;37(1):12-6. doi: 10.1007/s11239-013-1001-1.
PMID: 24163053BACKGROUNDLandry P, Plante I, Ouellet DL, Perron MP, Rousseau G, Provost P. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol. 2009 Sep;16(9):961-6. doi: 10.1038/nsmb.1651. Epub 2009 Aug 9.
PMID: 19668211BACKGROUNDDangelmaier C, Jin J, Smith JB, Kunapuli SP. Potentiation of thromboxane A2-induced platelet secretion by Gi signaling through the phosphoinositide-3 kinase pathway. Thromb Haemost. 2001 Feb;85(2):341-8.
PMID: 11246558BACKGROUNDLi C, Fang Z, Jiang T, Zhang Q, Liu C, Zhang C, Xiang Y. Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris. BMC Med Genomics. 2013 May 4;6:16. doi: 10.1186/1755-8794-6-16.
PMID: 23641832BACKGROUNDNagalla S, Shaw C, Kong X, Kondkar AA, Edelstein LC, Ma L, Chen J, McKnight GS, Lopez JA, Yang L, Jin Y, Bray MS, Leal SM, Dong JF, Bray PF. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood. 2011 May 12;117(19):5189-97. doi: 10.1182/blood-2010-09-299719. Epub 2011 Mar 17.
PMID: 21415270BACKGROUNDKatz MG, Fargnoli AS, Williams RD, Kendle AP, Steuerwald NM, Bridges CR. MiRNAs as potential molecular targets in heart failure. Future Cardiol. 2014 Nov;10(6):789-800. doi: 10.2217/fca.14.64.
PMID: 25495820BACKGROUNDSong MA, Paradis AN, Gay MS, Shin J, Zhang L. Differential expression of microRNAs in ischemic heart disease. Drug Discov Today. 2015 Feb;20(2):223-35. doi: 10.1016/j.drudis.2014.10.004. Epub 2014 Oct 23.
PMID: 25461956BACKGROUNDMitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008 Jul 29;105(30):10513-8. doi: 10.1073/pnas.0804549105. Epub 2008 Jul 28.
PMID: 18663219BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Chunjian Li
The First Affiliated Hospital with Nanjing Medical University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
May 5, 2015
First Posted
May 19, 2015
Study Start
January 1, 2015
Primary Completion
December 1, 2016
Study Completion
December 1, 2016
Last Updated
February 15, 2016
Record last verified: 2016-02