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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Moo Hyun Kim, Dong-A University
ClinicalTrials.gov Identifier:
NCT02070159
First received: February 8, 2014
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Coronary Artery Disease
Drug: Clopidogrel 600 mg
Drug: Prasugrel 30 mg
Drug: Prasugrel 60 mg
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Dong-A University:

Primary Outcome Measures:
  • Platelet reactivity [ Time Frame: at 6 hours after administration of study drug. (2 hours for prasugrel groups) ] [ Designated as safety issue: No ]

    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:
  • Percent inhibition [ Time Frame: at 6 hours after administration of study drug. (2 hours for prasugrel groups) ] [ Designated as safety issue: No ]

    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 [ Time Frame: at 6 hours after administration of study drug. (2 hours for prasugrel groups) ] [ Designated as safety issue: No ]
    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 [ Time Frame: at 6 hours after administration of study drug. (2 hours for prasugrel groups) ] [ Designated as safety issue: No ]

    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 [ Time Frame: 30 days after study drug administration ] [ Designated as safety issue: Yes ]
    Any event related to bleeding including access site bleeding and peri-procedural bleeding based on BARC and ACUITY criteria.

  • Adverse reaction [ Time Frame: 30 days after study drug administration ] [ Designated as safety issue: Yes ]
    Any adverse reaction related to study drug.


Enrollment: 43
Study Start Date: December 2011
Study Completion Date: January 2013
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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 Name: Effient 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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT02070159

Locations
Korea, Republic of
DongA University Hospital
Busan, Korea, Republic of, 602-715
Sponsors and Collaborators
Dong-A University
  More Information

Publications:
Responsible Party: Moo Hyun Kim, MD. Director, Regional Clinical Trial Center. Professor, Dept. of Cardiology Dong-A University Hospital, Dong-A University
ClinicalTrials.gov Identifier: NCT02070159     History of Changes
Other Study ID Numbers: PRELOAD-LD
Study First Received: February 8, 2014
Last Updated: February 21, 2014
Health Authority: Korea: Institutional Review Board

Keywords provided by Dong-A University:
coronary artery disease
prasugrel
platelet function tests

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Clopidogrel
Prasugrel
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 22, 2014