Phase 4 N=14 Randomized Treatment

Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-function: a Validation Study

Coronary Artery Disease

Bottom Line

View on ClinicalTrials.gov: NCT03489863 ↗

Enrolled (actual)

Serious AEs

0.0%

Results posted

Aug 2020

Primary outcome: Primary: P2Y12 Reaction Unit (PRU) — 5; 24 PRU — p=<0.05

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: Prasugrel (Drug); Ticagrelor (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: University of Florida
Primary completion: Mar 2019

Outcome Measures

Outcome	Result	p-value
PRIMARY P2Y12 Reaction Unit (PRU)	5; 24	<0.05 sig

Summary

Polymorphisms of the cytochrome P450 (CYP) 2C19 enzyme has been consistently shown to modulate clopidogrel response. Accordingly, the Food and Drug Administration (FDA) has issued a warning on the potential for reduced efficacy of clopidogrel among carriers of loss-of-function alleles (LOF) for CYP2C19 and suggest considering alternative antiplatelet therapies for these individuals. The pharmacodynamic (PD) effects of prasugrel and ticagrelor are not affected by CYP2C19 genetic polymorphisms. However, to date there are no head-to-head PD comparisons between these agents among patients with different CYP2C19 genetic polymorphisms, which is currently under investigation in CAD patients undergoing PCI at UF Health-Jacksonville (UFJ 2014-12, NCT 02065479). In order to rule out play of chance findings, pharmacogenetic investigations require external validation cohorts to support the study findings. Therefore, the present randomized study is designed to serve as an external validation cohort conducted in patients with established CAD not undergoing PCI testing the non-inferiority in platelet reactivity of prasugrel versus ticagrelor among CYP2C19 LOF allele carriers.

Eligibility Criteria

Inclusion criteria

Patients with CAD [defined as the presence of at least a 50% stenosis in a major epicardial vessel or major branch, or any prior coronary revascularization (PCI or coronary bypass graft surgery)] on treatment with either aspirin (81mg/day) or aspirin and clopidogrel (75m/day) for at least 30 days as per standard of care
Participated in UFJ 2016-14 study with genetic buccal swab test and have at least one CYP 2C19 LOF allele (CYP2C19*2 and CYP2C19*3)
Women of childbearing age must use reliable birth control (i.e. oral contraceptives) while participating in the study.

Exclusion criteria

Known allergies to prasugrel or ticagrelor
Weight <60kg
Considered at high risk for bleeding
Currently active bleeding
History of ischemic or hemorrhagic stroke or transient ischemic attack, or intracranial hemorrhage
Known severe hepatic dysfunction
On treatment with oral anticoagulant therapy (Vitamin K antagonists, dabigatran, apixaban, rivaroxaban)
Platelet count <80x106/mL
Hemoglobin <10 g/dL.
Creatinine Clearance <30 mL/minute
Patients with sick sinus syndrome (SSS) or high degree AV block without pacemaker protection.
Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with ticagrelor): CYP3A Inhibitors (ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin ) and CYP3A Inducers (rifampin, phenytoin, carbamazepine, and phenobarbital)
Pregnant or breastfeeding females

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Data sourced from ClinicalTrials.gov (NCT03489863). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.