Study of alterations in the CYP2C19 gene and platelet activity in patients submitted to coronary angioplasty

• Register: REBEC
• Last refreshed on: 29 May 2023
• Main ID: RBR-6n87rs
• Date of registration: 05/01/2015
• Prospective Registration: No
• Primary sponsor: Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
• Public title: Study of alterations in the CYP2C19 gene and platelet activity in patients submitted to coronary angioplasty
• Scientific title: Study of CYP2C19, ABCB1 and PON1 polymorphism in patients submitted to percutaneous coronary intervention and correlation to platelet aggregation in a brazilian population receiving simple and double anti-platelet therapy - SPARC: Sequence variation on Platelet Activation in Response to Clopidogrel and aspirin
• Date of first enrolment: 01/01/2010
• Recruitment status: Recruitment completed
• URL: http://ensaiosclinicos.gov.br/rg/RBR-6n87rs
• Study type: Observational
• Study design: Cohort prospective observational study
• Phase: N/A

Countries of recruitment

Brazil

Contacts

• Name: Julio Flavio Marchini
• Affiliation: Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

• Name: Julio F Marchini
• Affiliation: Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Key inclusion & exclusion criteria

Inclusion criteria: Consecutive patients submitted to percutaneous coronary intervention at the interventional cardiology unit at FMRP-USP.
Agreement with the consent form.
Exclusion criteria: Patients submitted only to balloon angioplasty or with contraindication to clopidogrel use.

Age minimum: 18Y
Age maximum:
Gender: -

Health Condition(s) or Problem(s) studied

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Coronary atherosclerotic disease, Platelet Aggregation, Cytochrome P-450 Enzyme System

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Intervention(s)

At the index procedure, a blood sample from the patients will be obtained for DNA isolation. It will be used to identify polymorphisms in genes CYP2C19, PON1 and ABCB1. A sample size of 200 patients was calculated for a 5% confidence interval for the rare allele. A second blood sample will be used to measure platelet activity through light transmission aggregometry.
Patientes will be followed up for a year after their coronary intervention. In this year, where they already have clinically preset visits, clinical data, medication use and event occurrence will be obtained. Preset visits occur at 30 days, 3 months, 6 months and 1 year after the coronary intervention.
Two additional blood samples will be drawn to measure platelet aggregation when the patient no longer needs the recomended clopidogrel

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Genetics

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Other

Primary Outcome(s)

Evalauting the percentage of patients carrying genetic polymorphisms in the CYP2C19, PON1 and ABCB1 genes (1), veryfied though the Drug Metabolism Genotyping Assay (2) with a significant difference of at least 5% when compared to gene polymorphisms in other populations (3)
Expected outcomes: CYP2C19*2: 75 % normal homozygotes, 20% de heterozigotes e 5% altered homozigotes. ABCB1: 22% normal homozigotes, 50% heterozigotes, 28% altered homozigotes alterado. PON1: 10% normal homozigotes, 50% heterozigotos e 40% altered homozigotes.

Comparison of patient platelet aggregometry (1) through light transmission aggregomety (2) in three time points, with double antiplatelet therapy, with aspirin only, and with clopidogrel only.
In the case of aspirin, arachdonic acid is used to stimulate platelets. Aspirin resistance is considered when less than 80% of light is transmitted with 5 minutes of the assay.
In the case of clopidogrel, ADP is used to stimulate platelets. Clopidogrel resistance is considered when less than 86% of light is transmitted with 5 minutes of the assay.
Expected outcomes: 14.7% of clopidogrel resistance and 5% aspirin resistance.

Secondary Outcome(s)

The secondary endpoint is a composite of cardiac death, non-fatal myocardial infarction, stroke, new ischemia-guided revascularization and stent thrombosis (1) that will be evaluated through the patient follow-up and by going after the patient or his family if he does not show up at the follow-up visits until the end of the year (2) Expected outcome: we expect 7 to 8% of events in the first year.

Source(s) of Monetary Support

Fundação de Amparo à Pesquisa do Estado de São Paulo

Secondary Sponsor(s)

Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo