Clinical trial NCT02394145: Genotype and Platelet Reactivity in Patients on Hemodialysis
Official title: The Relationship Between Genotype and Platelet Reactivity in Patients Treated With Ticagrelor Versus Clopidogrel: PIANO Genotype Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: platelet
ticagrelor
clopidogrel
end stage renal disease
hemodialysis
genetics
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
First posted: 2015-03-20
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The difference of antiplatelet effects according to genotype
timeFrame: 14 days after study drug treatment
Secondary outcomes:
measure: The difference of antiplatelet effects according to kidney function
timeFrame: 14 days after study drug treatment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
Study officials:
affiliation: Kyung Hee University Hospital
name: Weon Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.