PRAsugrel or clopIdogrel In Acute Coronary SyndromE With CYP2C19 GENEtic Variants

Acute Coronary Syndromes Clinical Trial

— PRAISE-GENE  

Official title:

Phase 3 Study Comparing the Efficacy and Safety of Prasugrel and Clopidogrel in Acute Coronary Syndrome Patients With CYP2C19 Polymorphism Who Undergo Percutaneous Coronary Intervention.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01641510
• Other study ID #: PRAISE-GENE
• Status: Completed
• Phase: Phase 3
• Start date: October 2013
• Est. completion date: February 2019

Study information

• Verified date: February 2019
• Source: Dong-A University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators hypothesize that reduced loading dose of prasugrel followed by reduced maintenance dose of prasugrel in acute coronary syndrome patients with CYP2C19 polymorphism undergoing percutaneous coronary intervention might exhibit lower platelet reactivity 24 hours and 30 days later which is associated with major adverse cardiovascular events.

Description:

Antiplatelet treatment is recommended worldwide for the secondary prevention and clopidogrel is an essential drug. But clopidogrel has limited value because of its pharmacodynamic interpatient variability and delayed onset time.

It is well known that patients who carry a common reduced-function CYP2C19 allele have a lower level of active metabolite of clopidogrel, diminished platelet inhibition, and furthermore, higher rate of major adverse cardiovascular events than noncarriers.

To achieve maximum plateau more rapidly and reduce the rate of high on-treatment platelet reactivity, higher loading dose of clopidogrel, up to 600 mg, is recommended. Although, however, the higher loading dose of clopidogrel, many patients still remain as non-responder.

Incidence of patients with clopidogrel resistance, especially CYP2C19*2 and *3, which encounter loss function, is higher in Eastern Asian peoples than Western peoples. Some studies report incidence rate of clopidogrel resistance in Eastern Asian peoples up to 99%.

However, the metabolism is not influenced by the presence of CYP2C19 genetic variation and prasugrel shows potent platelet inhibition. Although prasugrel exhibit potent platelet inhibition, recent reports describe the possible over inhibition of platelet especially in the East Asian people.

The investigators are going to compare the efficacy and safety of loading dose of prasugrel 30 mg which is lower than conventional loading dose followed by 5 mg/day which is also lower than conventional maintenance dose for 30 days and loading dose of clopidogrel 600 mg followed by 75 mg/day for 30 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2019
• Est. primary completion date: October 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 80 Years

Eligibility

Inclusion Criteria:

• Acute coronary syndrome

• Patients planned to undergo percutaneous transluminal coronary angioplasty

• Patients who agreed to the experimental plan which was permitted by IRB

Exclusion Criteria:

• Low body weight (< 50kg)

• History of stroke or transient ischemic attack

• History of upper gastrointestinal bleeding in recent 6 months

• Renal dysfunction defined by serum creatinine > 2.5 mg/dl

• Severe hepatic dysfunction defined by Child-Pugh criteria B or C

• Bleeding tendency

• Anticoagulation treatment including warfarin

• Thrombocytopenia defined by platelet < 100,000/ml

• Anemia defined by hemoglobin < 10 g/dl

• Contraindication for antiplatelet treatment or anticoagulation treatment

• History of administer glycoprotein IIb/IIIa inhibitor in recent 24hrs or planned to

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Acute Coronary Syndromes
• Syndrome

Intervention

Drug:
• Prasugrel
Loading with prasugrel 30 mg followed by daily administration of prasugrel 5 mg
• Clopidogrel
Loading with clopidogrel 600 mg followed by daily administration of clopidogrel 75 mg

Locations

Country	Name	City	State
Korea, Republic of	DongA University Hospital	Busan

Sponsors (1)

Lead Sponsor	Collaborator
Dong-A University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HPR 1 day	High platelet reactivity unit defined as platelet reactivity of 242u or more using VerifyNow method at 24 hours after PCI	24 hours after PCI
Secondary	MACE	Major adverse cardiovascular events consist of cardiac death, myocardial infarction, stroke, stent thrombosis, cardiac enzyme (CRP, CK-MB, Troponin-I)	30 days
Secondary	Bleeding	Major, minor or minimal bleeding defined by TIMI(thrombolysis in myocardial infarction) bleeding criteria	30 days
Secondary	HPRs	High platelet reactivity unit defined as platelet reactivity of 240u or more using VerifyNow method at 4 hours and 30 days after PCI	4 hours after PCI, 30 days after PCI
Secondary	HPR by VASP at 24 hours	HPR defined by VASP at 24 hours after PCI	24 hours from PCI
Secondary	HPR by VASP at 30 days	HPR by VASP at 30 days from PCI	30 days from PCI