Clinical trial NCT02163954: ONSET and OFFSET of Ticagrelor in ESRD
Official title: Platelet Reactivity in Patients With End Stage Renal Disease Receiving Clopidogrel Compared With Ticagrelor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: platelet
ticagrelor
clopidogrel
end stage renal disease
hemodialysis
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
Collaborators: name: Kyunghee University
First posted: 2014-06-16
Enrollment: 16
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Patients with severe chronic kidney disease or end stage renal disease (ESRD) on hemodialysis (HD) exhibited higher platelet reactivity to clopidogrel than did those with normal renal function. Not enough study has been conducted about the antiplatelet effects of ticagrelor in these cardiovascular high risk patients. We hypothesized ticagrelor would achieve more and faster antiplatelet effects compared with clopidogrel 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. Recently, we demonstrated that 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. One of good option to overcome high platelet reactivity in ESRD patients would be ticagrelor which has been already shown improved clinical outcomes. But little is known the antiplatelet effects of ticagrelor in ESRD patients on HD. The present study was designed to determine the antiplatelet effect as well as the onset and offset action of ticagrelor compared with clopidogrel in patients with ESRD undergoing maintenance HD.

Eligibility criteria: 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

Primary outcomes:
measure: The difference of antiplatelet effects assessed by VerifyNow assay
timeFrame: 14 days after study drug treatment
Secondary outcomes:
measure: the rate of onset and offset of the antiplatelet effects
timeFrame: 14 days after study drugs treatment
Other outcomes:
measure: Adverse events
timeFrame: during study period
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.