Chronic Kidney Disease
Conditions
Keywords
platelet, ticagrelor, clopidogrel, end stage renal disease, hemodialysis
Brief summary
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
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.
Interventions
DRUGTicagrelor
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
Sponsors
Kyunghee University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The difference of antiplatelet effects assessed by VerifyNow assay | 14 days after study drug treatment | The difference of PRU values achieved following antiplatelet therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The difference of antiplatelet effects assessed by light aggregometry assay | 14 days after study drug treatment | The difference of IPA values achieved following antiplatelet therapy |
| The difference of endothelial function assessed by forearm flow-mediated vasodilation (FMD) and peripheral arterial tonometry (PAT) | 14 days after study drug treatment | The difference of endothelial functions achieved following antiplatelet therapy |
| The difference of anti-inflammatory biomarkers | 14 days after study drug treatment | The difference of hsCRP, CD40, P-selectin, and IL-6 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | 6 weeks | Adverse events such as bleeding |
Countries
South Korea
Contacts
Primary ContactWeon Kim, MD, PhD
Backup ContactJong Shin Woo, MD, PhD
Outcome results
None listed