ONSET and OFFSET of Ticagrelor in ESRD

Study Overview
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Brief Summary
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Patients with severe chronic kidney disease or end stage renal disease (ESRD) on hemodialysis (HD) exhibited higher platelet reactivity to clopidogrel than did those with normal renal function. Not enough study has been conducted about the antiplatelet effects of ticagrelor in these cardiovascular high risk patients. We hypothesized ticagrelor would achieve more and faster antiplatelet effects compared with clopidogrel in ESRD patients on HD.

Detailed Description
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Chronic kidney disease (CKD) is a strong risk factor for cardiovascular morbidity and mortality, and confers an increasing risk of stent thrombosis even when dual antiplatelet therapy (clopidogrel and aspirin) is administered. Recently, we demonstrated that patients with severe CKD or end stage renal disease (ESRD) on hemodialysis (HD) exhibited higher platelet reactivity to clopidogrel than did those with normal renal function. One of good option to overcome high platelet reactivity in ESRD patients would be ticagrelor which has been already shown improved clinical outcomes. But little is known the antiplatelet effects of ticagrelor in ESRD patients on HD. The present study was designed to determine the antiplatelet effect as well as the onset and offset action of ticagrelor compared with clopidogrel in patients with ESRD undergoing maintenance HD.

Official Title
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Platelet Reactivity in Patients With End Stage Renal Disease Receiving Clopidogrel Compared With Ticagrelor

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Ticagrelor
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ESRD patients undergoing regular (≥ 6 months) maintenance HD ongoing (≥ 2 months) treatment with clopidogrel P2Y12 reaction units (PRUs) were more than 235 Exclusion Criteria: known allergies to aspirin, clopidogrel, or ticagrelor concomitant use of other antithrombotic drugs (oral anticoagulants, dipyridamole) thrombocytopenia (platelet count <100,000/mm3) hematocrit <25% uncontrolled hyperglycemia (hemoglobin A1c >10%) liver disease (bilirubin level >2 mg/dl) symptomatic severe pulmonary disease active bleeding or bleeding diathesis gastrointestinal bleeding within the last 6 months hemodynamic instability acute coronary or cerebrovascular event within the last 3 months pregnancy any malignancy concomitant use of a cytochrome P450 inhibitor or nonsteroidal 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: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Clopidogrel<br>Patients treated with clopidogrel for 14 days | Drug: Ticagrelor<br>* After randomization, an initial loading dose of ticagrelor (180 mg) was given and maintenance doses (ticagrelor 90 mg twice daily) was treated for 14 days.<br>* Other names: Ticagrelor (Brilinta);Drug: Clopidogrel<br>* After randomization, an initial loading dose of clopidogrel (300 mg) was given and maintenance doses (clopidogrel 75 mg once daily) was treated for 14 days.<br>* Other names: Clopidogrel (Plavix);|
| Experimental: Ticagrelor<br>Patients treated with ticagrelor for 14 days | Drug: Ticagrelor<br>* After randomization, an initial loading dose of ticagrelor (180 mg) was given and maintenance doses (ticagrelor 90 mg twice daily) was treated for 14 days.<br>* Other names: Ticagrelor (Brilinta);Drug: Clopidogrel<br>* After randomization, an initial loading dose of clopidogrel (300 mg) was given and maintenance doses (clopidogrel 75 mg once daily) was treated for 14 days.<br>* Other names: Clopidogrel (Plavix);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The difference of antiplatelet effects assessed by VerifyNow assay | The difference of PRU values achieved following antiplatelet therapy | 14 days after study drug treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the rate of onset and offset of the antiplatelet effects | the difference of slope during onset and offset of study drugs | 14 days after study drugs treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platelet, ticagrelor, clopidogrel, end stage renal disease, hemodialysis