Effect of Platelet Inhibition According to Clopidogrel Dose in Patients With Chronic Kidney Disease

Study Overview
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Brief Summary
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Impaired renal function is associated with reduced responsiveness to clopidogrel. There are no studies which have shown a means by which to overcome platelet hyporesponsiveness in patients with chronic kidney disease (CKD). The purpose of this study was to determine the functional impact of cilostazol in patients with CKD undergoing hemodialysis.

Detailed Description
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The aims of this study is to evaluate the effects of platelet responsiveness to clopidogrel or cilostazol in CKD patients undergoing hemodialysis. The differences in platelet activation markers are also evaluated before and after clopidogrel or cilostazol administration. The investigators will perform a prospective, randomized study to compare the degree of platelet inhibition and platelet activation markers by adjunctive cilostazol (100 mg twice daily) compared to clopidogrel (75 or 150 mg/day) in CKD patients undergoing hemodialysis.

Official Title
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Platelet Reactivity in Patients With Chronic Kidney Disease Receiving Adjunctive Cilostazol Compared to a High-maintenance Dose of Clopidogrel

Conditions
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Chronic Kidney Disease, Stable Angina

Intervention / Treatment
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* Drug: Clopidogrel, cilostazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease Exclusion Criteria: known allergies to aspirin, clopidogrel, or cilostazol thienopyridine use before enrollment concomitant use of other anti-thrombotic drugs (oral anticoagulants and dipyridamole) platelet count <100 x 106/μL hematocrit < 25% liver disease (bilirubin > 2 mg/dl) active bleeding or bleeding diathesis gastrointestinal bleeding within the last 6 months hemodynamic instability acute coronary or cerebrovascular event within 3 months malignancy concomitant use of a cytochrome P450 inhibitor or a non-steroidal anti-inflammatory drug recent treatment (<30 days) with a glycoprotein IIb/IIIa antagonist.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: clopidogrel 75 mg/day<br>CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease will be randomized to receive clopidogrel 75 mg/day for 14 days. | Drug: Clopidogrel, cilostazol<br>* Patients with CKD received clopidogrel (75 mg/day)for 14 days Patients with CKD received clopidogrel (150 mg/day)for 14 days Patients with CKD received clopidogrel (75 mg/day)and cilostazol (100 mg twice daily)for 14 days 75mg clopidogrel in patients with normal kidney function for 14 days<br>* Other names: pletaal;|
| Active Comparator: clopidogrel 150 mg/day<br>CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease will be randomized to receive clopidogrel 150 mg/day for 14 days. | Drug: Clopidogrel, cilostazol<br>* Patients with CKD received clopidogrel (75 mg/day)for 14 days Patients with CKD received clopidogrel (150 mg/day)for 14 days Patients with CKD received clopidogrel (75 mg/day)and cilostazol (100 mg twice daily)for 14 days 75mg clopidogrel in patients with normal kidney function for 14 days<br>* Other names: pletaal;|
| Active Comparator: adjunctive cilostazol<br>CKD patients undergoing chronic hemodialysis and PCI for stable coronary artery disease will be randomized to receive co-administration of adjunctive cilostazol (100 mg twice daily) and clopidogrel (75 mg/day; [group 3, 20 patients]) for 14 days. | Drug: Clopidogrel, cilostazol<br>* Patients with CKD received clopidogrel (75 mg/day)for 14 days Patients with CKD received clopidogrel (150 mg/day)for 14 days Patients with CKD received clopidogrel (75 mg/day)and cilostazol (100 mg twice daily)for 14 days 75mg clopidogrel in patients with normal kidney function for 14 days<br>* Other names: pletaal;|
| Active Comparator: 75mg clopidogrel<br>control group undergoing PCI for stable angina will be also maintained on clopidogrel (75 mg/day for 14 days). | Drug: Clopidogrel, cilostazol<br>* Patients with CKD received clopidogrel (75 mg/day)for 14 days Patients with CKD received clopidogrel (150 mg/day)for 14 days Patients with CKD received clopidogrel (75 mg/day)and cilostazol (100 mg twice daily)for 14 days 75mg clopidogrel in patients with normal kidney function for 14 days<br>* Other names: pletaal;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The differences of platelet aggregation according to the anti-platelet therapy. | Platelet function was assessed with light transmittance aggregometry and the VerifyNowTM P2Y12 assay. High on-treatment platelet reactivity was defined as 5 μmol/L of ADP-induced Aggmax > 50%. Inhibition of platelet aggregation (IPA) was defined as the percent decrease in aggregation values obtained at baseline and after treatment. VerifyNow-P2Y12 assay results are also assessed and expressed in P2Y12 reaction units (PRUs) and the percentage of inhibition. | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of platelet activation markers according to the anti-platelet therapy | Markers of platelet activation (soluble CD40 ligand [sCD40L] and soluble P-selectin [sP-selectin]) were assessed at baseline and after 14 days of anti-platelet therapy. | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet, cilostazol, clopidogrel, chronic kidney disease