Chronic Kidney Disease
Conditions
Keywords
platelet, ticagrelor, clopidogrel, end stage renal disease, hemodialysis, genetics
Brief summary
Patients with end stage renal disease (ESRD) on hemodialysis (HD) exhibited higher platelet reactivity to clopidogrel than did those with normal renal function. We 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 genetic influence in high platelet reactivity in patients with ESRD 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. We recently reported platelet inhibition by ticagrelor was markedly greater than by clopidogrel in patients with ESRD on HD. But exact mechanism of high platelet reactivity in ESRD patients was not fully evaluated. A possible postulation would be genetic influence. To investigate this issue, we will evaluate genetic polymorphism in patients with normal kidney function and ESRD on HD according to different doses of clopidogrel and ticagrelor. Genetic test will be assessed polymorphism of ABCB1, PON1, CYP2C19, CYP2C9 and P2Y12.
Interventions
DRUGTicagrelor
Patients with normal kidney function and ESRD on hemodialysis will be treated by ticagrelor 90mg twice a day for 14 days. After then, platelet reactivity will be assessed by light aggregometry and VerifyNow assay.
DRUGClopidogrel
Patients with normal kidney function and ESRD on hemodialysis will be treated by clopidogrel 75mg or 150mg once a day for 14 days. After then, platelet reactivity will be assessed by light aggregometry and VerifyNow assay.
Sponsors
Kyunghee University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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 * Matching patients with normal kidney function * documented coronary artery disease or high risk (Framingham heart risk score ≥ 20%) of coronary artery disease
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 according to genotype | 14 days after study drug treatment | The difference of P2Y12 reaction units (PRUs) according to genotype |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The difference of antiplatelet effects according to kidney function | 14 days after study drug treatment | The difference of P2Y12 reaction units (PRUs) according to kidney function |
Countries
South Korea
Contacts
Primary ContactWeon Kim, MD, PhD
Backup ContactJong Shin Woo, MD, PhD
Outcome results
None listed