There are 4 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).

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.

3 Assessment of Prospective CYP2C19 Genotype Guided Dosing of Anti-Platelet Therapy in Percutaneous Coronary Intervention (ADAPT)

This is a randomized, prospective, open label study to determine the cost-effectiveness of genotype-guided antiplatelet therapy. Patients undergoing percutaneous intervention (PCI) with stent implantation, will be randomized either to genotype guided dosing of antiplatelet therapy or usual care. The study utilizes a novel genotyping device, SpartanRx, to determine CYP2C19 genotypes from a buccal swab sample with 1 hour turnaround time.

NCT02508116 Acute Coronary Syndrome Cardiovascular Diseases Genetic: CYP2C19 genotyping

MeSH:Acute Coronary Syndrome Cardiovascular Diseases

HPO:Abnormality of the cardiovascular system

The most common loss of function (LOF) allele is *2 (c.681G>A; rs4244285), with frequencies of ~15% in Caucasians and Africans and 29-35% in Asians.

4 Clinical and Genetic Influencing Factors on Clozapine Pharmacokinetics in Schizophrenic Patients

Clozapine (Clz), an atypical antipsychotic, is the reference medication for patients with treatment-resistant schizophrenia. Due to the high inter-individual variability of its pharmacokinetics and its narrow therapeutic index, a close therapeutic drug monitoring (TDM) of Clz is highly recommended. Several factors can cause a variation in the pharmacokinetics as age, smoking habits, coffee consumption and drug interaction. Genetic factors related to hepatic expression levels of the cytochrome P450 (CYP), regulate the hepatic clearance of Clz, thereby determine its bioavailability. The CYP1A2 and CYP2C19 isoenzymes are mainly responsible for the metabolism of several drugs including Clz. It has been demonstrated that there is an interethnic variation in the expression and function of these two isoenzymes. This variation is caused by single nucleotide polymorphisms (SNPs) of genes encoding these proteins. While the Influence of the different polymorphisms related to CYP1A2 and CYP2C19 have been established especially in Asian and Caucasian populations, no study has examined the impact of these SNPs in the southern Mediterranean populations. Moreover, the impact of these SNPs is very controversial. The present study aims to investigate in Tunisian schizophrenic patients, the influence of genetic (CYP1A2 and CYP2C19 polymorphisms) and non-genetic factors on Clz pharmacokinetics.

NCT04240496 CYP1A2 Polymorphism CYP2C19 Polymorphism Clozapine Schizophrenia Other: Determination of plasma concentration of clozapine/ Genotyping

MeSH:Schizophrenia

HPO:Schizophrenia

Determination of the correlation between the presence of CYP1A2*1F (rs762551;-163C> A), CYP1A2*1C (rs2069514;-3860 G> A) and CYP 2C19*2 (rs4244285; 681G>A) and the variability of C0/Daily dose.. - Technique: PCR-RFLP (Polymerase Chain Reaction-Restriction Fragment Length Polymorphism).

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