Prasugrel With Lower Dose - Loading Dose (PRELOAD-LD)

Effect of Lower Loading Dose of Prasugrel Compared With Conventional Loading Dose of Clopidogrel and Prasugrel in Korean Coronary Artery Disease Patients Undergoing Coronary Angiography

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel 600 mg; Drug: Prasugrel 30 mg; Drug: Prasugrel 60 mg

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 Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • DongA University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Clopidogrel 600 mg; Patients administer conventional loading dose of clopidogrel 600 mg as active comparators.	Drug: Clopidogrel 600 mg; Patients administer 600 mg of clopidogrel as conventional loading dose of clopidogrel; Other Names: Plavix 600 mg
Experimental: Prasugrel 30 mg; Patients administer lower loading dose of prasugrel 30 mg.	Drug: Prasugrel 30 mg; Patients administer 30 mg of prasugrel as lower loading dose of prasugrel.; Other Names: Effient 30 mg
Active Comparator: Prasugrel 60 mg; Patients administer conventional loading dose of prasugrel 60 mg as active comparators.	Drug: Prasugrel 60 mg; Patients take 60 mg of prasugrel as conventional loading dose of prasugrel.; Other Names: Effient 60 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Platelet reactivity	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).	at 6 hours after administration of study drug. (2 hours for prasugrel groups)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent inhibition	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).	at 6 hours after administration of study drug. (2 hours for prasugrel groups)
HPR	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).	at 6 hours after administration of study drug. (2 hours for prasugrel groups)
LPR	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).	at 6 hours after administration of study drug. (2 hours for prasugrel groups)
Bleeding event	Any event related to bleeding including access site bleeding and peri-procedural bleeding based on BARC and ACUITY criteria.	30 days after study drug administration
Adverse reaction	Any adverse reaction related to study drug.	30 days after study drug administration

Collaborators and Investigators

• Sponsor: Dong-A University

Publications and helpful links

General Publications

• Kim MH, Zhang HZ, Jung DK. Pharmacodynamic comparisons for single loading doses of prasugrel (30 mg) and clopidogrel (600 mg) in healthy Korean volunteers. Circ J. 2013;77(5):1253-9. doi: 10.1253/circj.cj-12-0783. Epub 2013 Jan 30.

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: February 8, 2014
• First Submitted That Met QC Criteria: February 21, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): February 25, 2014
• Last Update Submitted That Met QC Criteria: February 21, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: coronary artery disease; prasugrel; platelet function tests
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; 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: PRELOAD-LD