Genetic Polymorphism Associated With Coronary Heart Disease Susceptibility and Variability of Clopidogrel Response

NCT03373552 | Active Not Recruiting

• 1 other identifier: FattoumaBourguiba
• Study Type: observational
• Target: 250
• Locations: 1 country
• Sites: 1

Brief Summary

The pathogenesis of CHD remains poorly known despite much research over the last few decades. Numerous non-genetic variables have been demonstrated to have a significant impact on the risk of CHD. However, the fact that many individuals with severe CHD do not have any of these non-genetic risk factors supports the notion that genetic factors play a role in the occurrence and progression of CHD. In this study, we investigated the association of polymorphisms affecting Vascular endothelial factors A (VEGFA) and its receptor VEGFR2 (rs3025039, rs699947, rs2305948, rs1870377), CXCR4 (rs2228014), CCR2 (rs1799864), C3 (rs2230199), CCL2 (rs1024611 and rs2857656) and CCL5 (rs2107538 and rs22280789) with CHD susceptibility and the severity of coronary lesion. On another side, clopidogrel is largely prescribed in association with aspirin in order to prevent atherothrombotic complications in patients with acute coronary syndrome. Its effectiveness is undeniably proven by several studies and clinical trials over the years, however, some patients have presented ischemic events such as thrombosis on stent or myocardial infarction despite a well-conducted treatment. This clopidogrel non-responsiveness is probably multifactorial; several genetic and non genetic factors may contribute to impaired platelet inhibition by clopidogrel. In this regard, it is meaningful to determine genetic polymorphisms contributing to the variability of clopidogrel response in patients with Coronary Artery Therefore, the goal of this study is to determine the impact of the polymorphisms, affecting CYP2C19, PON, ABCB1, ITGB3 and P2RY12 genes, on the response to clopidogrel in patients with CAD.Disease (CAD). In fact, the recognition of these factors might predict the exposure to the risk of thrombosis and cardiovascular death in these patients.

Conditions

Coronary Disease

Keywords

Coronary Disease; Polymorphism, genetic; Clopidogrel;

Outcome Measures

Primary Outcomes (1)

• Platelet reactivity on clopidogrel

  Platelet reactivity on clopidogrel is assessed by the VerifyNow P2Y12 assay

  at least after 10 days

Other Outcomes (1)

• Genotyping for genetic polymorphisms

  an average of 1 month

Study Arms (2)

non responder Group

Platelet function assay: High platelet reactivity: PRU\>208

Diagnostic Test: Platelet function assay

responder Group

Platelet function assay: PRU\<208

Diagnostic Test: Platelet function assay

Interventions

Platelet function assay DIAGNOSTIC_TEST

Platelet function assay

non responder Group; responder Group

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with coronary disease

You may qualify if:

• Patient \>20 years old
• Established coronary disease

You may not qualify if:

• Severe hepatic dysfunction
• Disease or active pathological bleeding (e.g., gastrointestinal (GI) bleeding)
• Use of glycoprotein IIb/IIIa inhibitors or cilostazol
• inability to give informed consent.

Sponsors & Collaborators

• Hôpital Universitaire Fattouma Bourguiba: lead

Study Sites (1)

Fattouma Bourguiba Hospital

Monastir, Monastir Governorate, 5000, Tunisia

Location

Related Publications (1)

• Chouchene S, Dabboubi R, Raddaoui H, Abroug H, Ben Hamda K, Hadj Fredj S, Abderrazak F, Gaaloul M, Rezek M, Neffeti F, Hellara I, Sassi M, Khefacha L, Sriha A, Nouira S, Najjar MF, Maatouk F, Messaoud T, Hassine M. Clopidogrel utilization in patients with coronary artery disease and diabetes mellitus: should we determine CYP2C19*2 genotype? Eur J Clin Pharmacol. 2018 Dec;74(12):1567-1574. doi: 10.1007/s00228-018-2530-5. Epub 2018 Aug 3.

  PMID: 30073432 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Venous blood samples

MeSH Terms

Conditions

Coronary Disease

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Study Officials

• chouchene saoussen, assistant

  Fattouma Bourguiba Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Assistant in hematology

Study Record Dates

• First Submitted: December 7, 2017
• First Posted: December 14, 2017
• Study Start: August 12, 2015
• Primary Completion (Estimated): November 15, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: February 27, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)