SNPMiner Trials by Shray Alag

SNPMiner SNPMiner Trials (Home Page)

Report for SNP rs4986893

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 2 clinical trials

Clinical Trials

1 Comparison of Platelet Inhibitory Effect With Adjunctive Cilostazol Versus High Maintenance-dose ClopidogrEL in Acute Myocardial Infarction Patients According to CYP2C19 Polymorphism

Percutaneous coronary intervention (PCI) with stent implantation is the preferred reperfusion strategy for treatment of acute myocardial infarction (AMI). Despite advances in both devices and pharmacological support for AMI patients undergoing PCI, the risk of recurrent ischemic events has been higher than that of elective PCI. Among therapeutic options for surmounting clopidogrel hyporesponsiveness, higher loading doses and maintenance doses of clopidogrel achieved significant enhancements in the speed of onset and intensity of inhibition and these approaches have been widely adapted in clinical practice. Interestingly, recent studies found that carriers of the loss-of-function hepatic cytochrome (CYP) 2C19 allele had significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of major adverse cardiovascular events than did non-carriers, in the setting of PCI and acute coronary syndrome (ACS). These findings raise the need of solutions to overcome enhanced post-clopidogrel platelet reactivity by the influence of the loss-of-function CYP2C19 allele. Increasing the dose of clopidogrel, new potent P2Y12 antagonists (such as prasugrel), or other antiplatelet drugs such as cilostazol may be alternative antiplatelet regimens in patients with the loss-of-function CYP variant. A recent study demonstrated that adjunctive cilostazol to dual antiplatelet therapy (triple antiplatelet therapy) intensified platelet inhibition as compared with a high maintenance-dose (MD) of 150 mg/day. Therefore, triple antiplatelet therapy could also be an alternative antiplatelet therapy to improve platelet inhibition and clinical outcomes in carriers of CYP2C19 mutant allele. The purpose of this study was to determine the impact of adjunctive cilostazol on platelet inhibition in carriers and non-carriers of the loss-of-function CYP2C19 allele. The investigators compared the enhanced inhibition of platelet aggregation by adjunctive cilostazol 100 mg twice daily versus high-MD clopidogrel 150 mg/day in AMI patients treated with emergent coronary stenting, according to the CYP2C19 polymorphism.

NCT00915733 Myocardial Infarction Drug: cilostazol Drug: clopidogrel (Plavix) Genetic: CYP2C19 Drug: aspirin (Acetylsalicylic acid)
MeSH:Myocardial Infarction Infarction
HPO:Myocardial infarction

2. Two CYP2C19 polymorphisms, CYP2C19*2 (rs4244285, c. 681G>A, p.P227P), and CYP2C19*3 (rs4986893, c. 636G>A, p. W212X), are investigated using the ABI SNaPshot reaction and the ABI 3100 automated genetic analyzer (Applied Biosystems, Foster City, CA, USA).

Primary Outcomes

Measure: Absolute reduction of maximal platelet aggregation (Aggmax) by 5 & 20 μM ADP induced LTA

Time: 30 days

Secondary Outcomes

Measure: Absolute reduction of late platelet aggregation (Agglate) by 5 & 20 μM ADP induced LTA

Time: 30 days

Measure: Absolute reduction of P2Y12 reaction unit (PRU)

Time: 30 days

Measure: The rate of high post-treatment platelet reactivity

Time: 30 days

2 Clopidogrel Pharmacogenetic Score System Established for Chinese Patients

The aim of the present study is to evaluate candidate variables,including Cytochrome P450 2C19(CYP2C19) genotypes, clinical and demographic variables,to establish a simple risk score that can be easily adopted by clinicians to identify patients who are at risk for HPR and composite cardiovascular outcomes in Chinese Han patients treated with dual antiplatelet therapy.

NCT01990989 Acute Coronary Syndrome
MeSH:Acute Coronary Syndrome

The loss of function alleles, CYP2C19*2 (rs4244285) and CYP2C19*3 (rs4986893), will be genotyped by the polymerase chain reaction(PCR)-ligase detection reactions(LDR)sequencing method.

Primary Outcomes

Description: A threshold of 50% maximal post-procedural aggregation was chosen to define HPR.

Measure: high on-treatment platelet reactivity (HPR)

Time: After 30 days maintenance dose of clopidogrel administration

Secondary Outcomes

Description: The composite of death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke , urgent coronal revascularization,and stent thrombosis.

Measure: Composite ischemia cardiovascular outcomes

Time: 1 year

Description: The primary clinical safety end point of the study is the 1-year incidence of combined major and minor bleeding events defined according to the Thrombolysis in Myocardial Infarction (TIMI) criteria . TIMI major bleedings include hemoglobin reduction >5 g/dL(with or without obvious bleeding spots) , intracranial hemorrhages, and cardiac tamponade.TIMI minor bleedings include hemoglobin reduction >3 g/dL but ≤5 g/dL ,macroscopic hematuria,hemoptysis,hematemesis,ecchymoma,mucous membrane and other minor bleedings.

Measure: Hemorrhagic complications

Time: 1 year

HPO Nodes