Prasugrel With Lower Dose - Loading Dose

Phase 3

Completed

• Conditions: Coronary Artery Disease
• Interventions: Drug: Prasugrel 60 mg; Drug: Clopidogrel 600 mg; Drug: Prasugrel 30 mg

• Registration Number: NCT02070159
• Lead Sponsor: Dong-A University

Brief Summary

Although prasugrel, recently available thienopyridine derivative, exhibits rapid and potent platelet inhibition, concerns of low on-treatment platelet reactivity have been suggested especially in East Asian ethnicities. The investigators compared the effect of lower loading dose of prasugrel with conventional loading dose of clopidogrel and prasugrel.

Detailed Description

Although clopidogrel together aspirin has been a backbone of anti-platelet therapy in coronary artery disease patients, clopidogrel has several limitations. It has delayed onset of peak concentration and pharmacodynamic inter-patient response variability resulting in high on-treatment platelet reactivity (HPR). Those demerits are known to be associated with adverse cardiovascular outcomes.

Prasugrel has a more effective metabolism pathway than clopidogrel and exhibits more rapid and potent platelet inhibition. Recent guidelines recommend prasugrel as a first line antiplatelet agent or put precedence over clopidogrel for the patients with acute coronary syndrome. However, there have been concerns of different pharmacodynamic and pharmacokinetic response to prasugrel in East Asian ethnicities.

In addition, lower loading dose of prasugrel exhibited more potent pharmacodynamic effect than clopidogrel 600 mg with comparable efficacy compared to conventional loading dose of prasugrel in healthy Korean subjects.

The investigators compare the antiplatelet effect of lower loading dose of prasugrel 30 mg with conventional loading dose of clopidogrel 600 mg and prasugrel 60 mg in Korean coronary artery disease patients undergoing elective coronary angiography.

Study Timeline

• Study Start: 2011-12
• Primary Completion: 2012-12
• Study Completion: 2013-01
• Status Verified: 2014-02
• Study First Submitted: 2014-02-08
• Study First Submitted QC: 2014-02-21
• Last Update Submitted: 2014-02-21
• Study First Posted: 2014-02-25
• Last Update Posted: 2014-02-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Patients between 18 and 80 years
• Stable or unstable angina
• Planned to undergo elective coronary angiography

Exclusion Criteria

• Previous history of transient ischemic attack or stroke
• Intracranial neoplasm
• Uncontrolled malignant disease
• History of antiplatelet or anticoagulation treatment within 1 month
• Contraindication to the study drug
• Bleeding diathesis
• Hemoglobin < 10 g/dl
• Platelet count < 100,000/mm3
• Significant renal insufficiency (glomerular filtration rate <60 mL/min/1.73 m2)
• Significant hepatic impairment (Serum liver enzyme or bilirubin > 3 times normal limit)
• Body weight < 50 kg

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prasugrel 60 mg	Prasugrel 60 mg	Patients administer conventional loading dose of prasugrel 60 mg as active comparators.
Clopidogrel 600 mg	Clopidogrel 600 mg	Patients administer conventional loading dose of clopidogrel 600 mg as active comparators.
Prasugrel 30 mg	Prasugrel 30 mg	Patients administer lower loading dose of prasugrel 30 mg.

Primary Outcome Measures

Name	Time	Method
Platelet reactivity	at 6 hours after administration of study drug. (2 hours for prasugrel groups)	Platelet reactivity was measured using traditional light transmission aggregometry (LTA), VerifyNow (Accumetrics, San Diego, CA, USA), and multiple electrode aggregometry (MEA, Dynabyte Medical, Munich, Germany).; The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups).

Secondary Outcome Measures

Name	Time	Method
Percent inhibition	at 6 hours after administration of study drug. (2 hours for prasugrel groups)	Percent inhibition is calculated using the following fomula: % inhibition = \[(baseline reactivity unit - peak reactivity unit) / baseline reactivity unit\] × 100.; Percent inhibition is measured at the time of peak platelet inhibition. The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups).
HPR	at 6 hours after administration of study drug. (2 hours for prasugrel groups)	The high platelet reactivity (HPR) was defined as the results of LTA ≥ 48% or ≥ 55%, PRU ≥ 242 or ≥ 275, and result of MEA assay ≥ 37 U or 54 U at the time of peak platelet inhibition The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups).
LPR	at 6 hours after administration of study drug. (2 hours for prasugrel groups)	The low platelet reactivity (LPR) was defined as LTA \< 12, PRU \< 85, MEA \< 19 at the time of peak platelet inhibition.; The platelet reactivity was measured at 6 hours after study drug administration (after 2 hours for the prasugrel groups).
Bleeding event	30 days after study drug administration	Any event related to bleeding including access site bleeding and peri-procedural bleeding based on BARC and ACUITY criteria.
Adverse reaction	30 days after study drug administration	Any adverse reaction related to study drug.

Trial Locations

Locations (1)

DongA University Hospital; 🇰🇷 Busan, Korea, Republic of