PRAsugrel or clopIdogrel In Acute Coronary SyndromE With CYP2C19 GENEtic Variants (PRAISE-GENE)

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.

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.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndromes
• Intervention / Treatment: Drug: Prasugrel; Drug: Clopidogrel

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • DongA University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prasugrel; Loading and maintenance dose of prasugrel	Drug: Prasugrel; Loading with prasugrel 30 mg followed by daily administration of prasugrel 5 mg; Other Names: Effient
Active Comparator: Clopidogrel; Loading and maintenance dose of clopidogrel	Drug: Clopidogrel; Loading with clopidogrel 600 mg followed by daily administration of clopidogrel 75 mg; Other Names: Plavix; Plavitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
MACE	Major adverse cardiovascular events consist of cardiac death, myocardial infarction, stroke, stent thrombosis, cardiac enzyme (CRP, CK-MB, Troponin-I)	30 days
Bleeding	Major, minor or minimal bleeding defined by TIMI(thrombolysis in myocardial infarction) bleeding criteria	30 days
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
HPR by VASP at 24 hours	HPR defined by VASP at 24 hours after PCI	24 hours from PCI
HPR by VASP at 30 days	HPR by VASP at 30 days from PCI	30 days from PCI

Collaborators and Investigators

• Sponsor: Dong-A University

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): February 1, 2019

Study Registration Dates

• First Submitted: July 2, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 16, 2012

Study Record Updates

• Last Update Posted (Actual): February 11, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: prasugrel; clopidogrel; high platelet reactivity; reduced-function CYP2C19 allele
• Additional Relevant MeSH Terms: Pathologic Processes; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Disease; Syndrome; Acute Coronary Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Prasugrel Hydrochloride
• Other Study ID Numbers: PRAISE-GENE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED