Genotype and Platelet Reactivity in Patients on Hemodialysis

Kyung Hee University

Status and phase: Unknown; Phase 3

Conditions: Chronic Kidney Disease

Treatments: Drug: Ticagrelor; Drug: Clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT02394145

PIANO-genetics

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 estimated patients

Sex: All

Ages: 20 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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20 participants in 5 patient groups

Ticagrelor 180mg in ESRD patients

Experimental group

Description:

After randomization, ESRD patients on HD will be treated by an initial loading dose of ticagrelor (180 mg) and maintenance doses (ticagrelor 90 mg twice daily) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Treatment:

Drug: Ticagrelor

Clopidogrel 75mg in ESRD patients

Active Comparator group

Description:

After randomization, ESRD patients on HD will be treated by an initial loading dose of clopidogrel 300 mg) and maintenance doses (clopidogrel 75 mg once a day) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Treatment:

Drug: Clopidogrel

Clopidogrel 150mg in ESRD patients

Active Comparator group

Description:

After randomization, ESRD patients on HD will be treated by an initial loading dose of clopidogrel 300 mg) and maintenance doses (clopidogrel 150 mg once a day) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Treatment:

Drug: Clopidogrel

Ticagrelor 180mg in normal kidney

Active Comparator group

Description:

After randomization, patients with normal kidney function will be treated by an initial loading dose of ticagrelor (180 mg) and maintenance doses (ticagrelor 90 mg twice daily) for 14 days. Platelet reactivity and genetic polymorphism will be assessed

Treatment:

Drug: Ticagrelor

Clopidogrel 75mg in normal kidney

Active Comparator group

Description:

After randomization, patients with normal kidney function will be treated by an initial loading dose of clopidogrel 300 mg) and maintenance doses (clopidogrel 75 mg once a day) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Treatment:

Drug: Clopidogrel