Genotype and Platelet Reactivity in Patients on Hemodialysis

Phase 3

• Conditions: Chronic Kidney Disease
• Interventions: Drug: Ticagrelor; Drug: Clopidogrel

• Registration Number: NCT02394145
• Lead Sponsor: Kyunghee University Medical Center

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.

Study Timeline

• Study Start: 2009-09
• Status Verified: 2015-03
• Study First Submitted: 2015-03-14
• Study First Submitted QC: 2015-03-19
• Last Update Submitted: 2015-03-19
• Study First Posted: 2015-03-20
• Last Update Posted: 2015-03-20
• Primary Completion: 2015-08
• Study Completion: 2015-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ticagrelor 180mg in ESRD patients	Ticagrelor	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.
Clopidogrel 150mg in ESRD patients	Clopidogrel	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.
Clopidogrel 75mg in ESRD patients	Clopidogrel	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.
Ticagrelor 180mg in normal kidney	Ticagrelor	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
Clopidogrel 75mg in normal kidney	Clopidogrel	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Kyung Hee University Hospital; 🇰🇷 Seoul, Korea, Republic of