Plasma and Platelet microRNAs in Clopidogrel Low Response Patients

NCT ID: NCT02447809

Last Updated: 2016-02-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-31

Study Completion Date

2016-12-31

Brief Summary

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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

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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.

Conditions

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Coronary Artery Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

SINGLE

Participants

Study Groups

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Regular DAPT(IPA≤60%)

ASA and Clopidogrel

Group Type EXPERIMENTAL

Clopidogrel

Intervention Type DRUG

(ASA 100mg daily and Clopidogre 75mg daily)\* 12 month.

acetylsalicylic acid (ASA)

Intervention Type DRUG

Regular DAPT(IPA>60%)

ASA and Clopidogrel

Group Type ACTIVE_COMPARATOR

Clopidogrel

Intervention Type DRUG

(ASA 100mg daily and Clopidogre 75mg daily)\* 12 month.

acetylsalicylic acid (ASA)

Intervention Type DRUG

Interventions

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Clopidogrel

(ASA 100mg daily and Clopidogre 75mg daily)\* 12 month.

Intervention Type DRUG

acetylsalicylic acid (ASA)

Intervention Type DRUG

Other Intervention Names

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Plavix

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Natural Science Foundation of China

OTHER_GOV

Sponsor Role collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role lead

Responsible Party

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Chunjian Li

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Chunjian Li

Role: PRINCIPAL_INVESTIGATOR

The First Affiliated Hospital with Nanjing Medical University

Locations

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First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Chunjian Li, Ph.D

Role: CONTACT

+86-25-83718836 ext. 6018

Hui Zhu

Role: CONTACT

+86-25-83718836 ext. 6018

Facility Contacts

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Fuming Zhang, M.D.

Role: primary

+86-25-83718836 ext. 6360

Yi Chai, M.D.

Role: backup

+86-25-83718836 ext. 6360

References

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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.

Reference Type BACKGROUND
PMID: 11519503 (View on PubMed)

Siller-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.

Reference Type BACKGROUND
PMID: 24262612 (View on PubMed)

Calin 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.

Reference Type BACKGROUND
PMID: 16885332 (View on PubMed)

Hu 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.

Reference Type BACKGROUND
PMID: 20194856 (View on PubMed)

Clancy 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.

Reference Type BACKGROUND
PMID: 24163053 (View on PubMed)

Landry 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.

Reference Type BACKGROUND
PMID: 19668211 (View on PubMed)

Dangelmaier 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.

Reference Type BACKGROUND
PMID: 11246558 (View on PubMed)

Li 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.

Reference Type BACKGROUND
PMID: 23641832 (View on PubMed)

Nagalla 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.

Reference Type BACKGROUND
PMID: 21415270 (View on PubMed)

Katz 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.

Reference Type BACKGROUND
PMID: 25495820 (View on PubMed)

Song 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.

Reference Type BACKGROUND
PMID: 25461956 (View on PubMed)

Mitchell 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.

Reference Type BACKGROUND
PMID: 18663219 (View on PubMed)

Other Identifiers

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004

Identifier Type: -

Identifier Source: org_study_id

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