Platelet Function Assessment for Atherothrombotic Patients

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT00513149

Collaborator

(none)

150

Enrollment

Location

Arm

Duration (Months)

2.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Coronary Artery Disease	Drug: Clopidogrel	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jul 1, 2006

Anticipated Primary Completion Date :

Jun 1, 2011

Anticipated Study Completion Date :

Jul 1, 2011

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: c6

Clopidogrel 600 mg loading

Drug: Clopidogrel

Clopidogrel 600 mg loading

Outcome Measures

Primary Outcome Measures

the occurrence of major cardiovascular events (MACE)(death, myocardial infarction, stroke, and clinically driven target lesion revascularization) [1 year]

Secondary Outcome Measures

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]