Prasugrel With Lower Dose - Loading Dose

Coronary Artery Disease Clinical Trial

— PRELOAD-LD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02070159
• Other study ID #: PRELOAD-LD
• Status: Completed
• Phase: Phase 3
• First received: February 8, 2014
• Last updated: February 21, 2014
• Start date: December 2011
• Est. completion date: January 2013

Study information

• Verified date: February 2014
• Source: Dong-A University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Drug:
• Clopidogrel 600 mg
Patients administer 600 mg of clopidogrel as conventional loading dose of clopidogrel
• Prasugrel 30 mg
Patients administer 30 mg of prasugrel as lower loading dose of prasugrel.
• Prasugrel 60 mg
Patients take 60 mg of prasugrel as conventional loading dose of prasugrel.

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, 

References & Publications (1)

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. Epub 2013 Jan 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	Yes
Secondary	Adverse reaction	Any adverse reaction related to study drug.	30 days after study drug administration	Yes