Ticagrelor and Anti-inflammatory Effects

Study Overview
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Brief Summary
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Antiplatelet treatment in patients with end stage renal disease (ESRD) on hemodialysis (HD) is still challenging because of bleeding and thrombotic complications. The investigators hypothesized ticagrelor once daily dose would achieve tolerable antiplatelet effects compared with ticagrelor twice a day dose 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. 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. The investigators recently reported platelet inhibition by ticagrelor was faster and markedly greater than by clopidogrel with onset dosing regimen in patients with ESRD on HD. However, few studies have been conducted whether platelet reactivity during ticagrelor treatment is associated with endothelial function, platelet activation markers and inflammation status in ESRD patients on HD. Additionally, the dose dependent effects of ticagrelor have been rarely evaluated.

Official Title
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Relationship of Dose of Ticagrelor and Anti-inflammatory Effect in Patients With End Stage Renal Disease on Hemodialysis: PIANO-6 Randomized Crossover Study

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Ticagrelor


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 |
| --- | --- |
| Experimental: Ticagrelor 90 mg<br>After randomization, an initial loading dose of ticagrelor (180 mg) was given and low dose ticagrelor (ticagrelor 90 mg once a day) was treated for 14 days. | Drug: Ticagrelor<br>* After randomization, each group will be treated as assigned dose of ticagrelor (ticagrelor 90mg once a day or 90mg twice a day) for 14 days. After 1 week wash-out period, cross-over study will be performed<br>* Other names: Ticagrelor (Brilinta);|
| Active Comparator: Ticagrelor 180 mg<br>After randomization, an initial loading dose of ticagrelor (180 mg) was given and usual dose ticagrelor (ticagrelor 90 mg twice a day) was treated for 14 days. | Drug: Ticagrelor<br>* After randomization, each group will be treated as assigned dose of ticagrelor (ticagrelor 90mg once a day or 90mg twice a day) for 14 days. After 1 week wash-out period, cross-over study will be performed<br>* Other names: Ticagrelor (Brilinta);|

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 difference of antiplatelet effects assessed by light aggregometry assay | The difference of IPA values achieved following antiplatelet therapy | 14 days after study drug treatment | 
| The difference of endothelial function assessed by forearm flow-mediated vasodilation (FMD) and peripheral arterial tonometry (PAT) | The difference of endothelial functions achieved following antiplatelet therapy | 14 days after study drug treatment | 
| The difference of anti-inflammatory biomarkers | The difference of hsCRP, CD40, P-selectin, and IL-6 | 14 days after study drug 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