Platelet Function Assessment for Atherothrombotic Patients

Validation of the Clinical Applicability of Various Platelet Function Assessments in High-Risk Atherothrombotic Patients Undergoing Percutaneous Coronary Angioplasty: Phase 4 Study

Background-Despite the pivotal pathogenic role of platelets in atherothrombosis has been widely recognized, there is a striking lack of consensus regarding how to measure platelet function and how to monitor the effects of various antiplatelet drugs. In view of the fact that recurrent ischemic events occurred in 8.5% to 8.8% of patients treated with dual antiplatelet drugs and there is significant inter-individual variability in platelet reactivity, we believe that the importance of platelet function assessment and its clinical implication should not be overlooked.

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Clopidogrel

Detailed Description

Methods and Expected Results-In this prospective follow-up study, we will assess the predictive power of different assays of platelet function (PFA-100, plasma levels of von Willebrand factor, P-selectin, soluble CD40 ligand, and myeloid-related protein-8/14, and ADP-induced P-selectin [CD62P] expression on platelets by flow cytometry) before and after high-dose (600 mg) clopidogrel loading, at 3-month follow-up, and at study end on the occurrence of major cardiovascular events (MACE)(death, myocardial infarction, stroke, and coronary revascularization). We will also evaluate the correlations between different assays of platelet function. Based on our previous pilot study which demonstrated that a significant association between collagen-ADP closure time measured by PFA-100 and the occurrence of major cardiovascular events in 130 patients undergoing coronary angioplasty followed up for 6 months, we plan to include 150-200 patients into the present study. The total inclusion period is estimated to be 1 year. Therefore, a total of 2 to 2.5 years will be needed to complete this study. In the first year, we will analyze (1) the correlations between various platelet parameters and coronary angiographic findings; (2) the correlations among different platelet function measurements; and (3) the responsiveness of CADP-CT on high-dose clopidogrel loading.

In the second year, we will (1) analyze the predictability of various platelet parameters, at different point of time (baseline, after clopidogrel loading, at study end), on the occurrence of MACE and (2) establish a risk-prediction schema for patients undergoing coronary angioplasty. A pre-defined threshold value for the collagen-epinephrine closure time is set at 190 s, since this value has been recommended by other investigators to differentiate the presence or absence of aspirin resistance. A pre-defined threshold value for the collagen-ADP closure time is set at 90 s, since we found in our pilot study that this value was associated with the best discriminating ability for identifying patients developing MACE. In the third year, genetic background determining the PFA-100 closure time and levels of plasma markers of platelet activation will be explored by analyzing the relationships between various SNP/haplotype patterns and values of different platelet function assessments.

Clinical Significance-The present study will be the first to explore the clinical role of platelet function assessment both at baseline, after high-dose clopidogrel loading, and at study end. It may give us great insights regarding how to treat high-risk patients adequately with antiplatelet agents.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 100
    • Recruiting
    • Division of Cardiology, Department of Internal Medicine and Department of Medical Imaging, National Taiwan University Hospital
    • Contact: Tzung-Dau Wang, MD, PhD; Phone Number: 5632 886-2-2312-3456; Email: tdwang@ha.mc.ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Coronary artery disease

Exclusion Criteria:

• History of bleeding diathesis
• History of drug or alcohol abuse or liver disease
• Abnormal prothrombin time
• Abnormal platelet count
• Serum creatinine >1.5 mg/dl.

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

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: c6; Clopidogrel 600 mg loading	Drug: Clopidogrel; Clopidogrel 600 mg loading

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the occurrence of major cardiovascular events (MACE)(death, myocardial infarction, stroke, and clinically driven target lesion revascularization)	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
the correlations between various platelet parameters and coronary angiographic findings	1 year
the correlations among different platelet function measurements	1 year
the responsiveness of CADP-CT on high-dose clopidogrel loading	1 year

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Chair: Tzung-Dau Wang, M.D.,Ph.D., National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2006
• Primary Completion (Anticipated): June 1, 2011
• Study Completion (Anticipated): July 1, 2011

Study Registration Dates

• First Submitted: August 6, 2007
• First Submitted That Met QC Criteria: August 7, 2007
• First Posted (Estimate): August 8, 2007

Study Record Updates

• Last Update Posted (Estimate): January 24, 2011
• Last Update Submitted That Met QC Criteria: January 20, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: coronary artery disease; clopidogrel; angioplasty; PFA
• 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
• Other Study ID Numbers: 200612040R