Clinical trial NCT02406911: Ticagrelor and Anti-inflammatory Effects
Official title: Relationship of Dose of Ticagrelor and Anti-inflammatory Effect in Patients With End Stage Renal Disease on Hemodialysis: PIANO-6 Randomized Crossover Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chronic Kidney Disease
Keywords: platelet
ticagrelor
clopidogrel
end stage renal disease
hemodialysis
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
First posted: 2015-04-02
Enrollment: 25
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: Antiplatelet treatment in patients with end stage renal disease (ESRD) on hemodialysis (HD) is still challenging because of bleeding and thrombotic complications. The investigators hypothesized ticagrelor once daily dose would achieve tolerable antiplatelet effects compared with ticagrelor twice a day dose 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. 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. The investigators 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 whether platelet reactivity during ticagrelor treatment is associated with endothelial function, platelet activation markers and inflammation status in ESRD patients on HD. Additionally, the dose dependent effects of ticagrelor have been rarely evaluated.

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 difference of antiplatelet effects assessed by light aggregometry assay
timeFrame: 14 days after study drug treatment
measure: The difference of endothelial function assessed by forearm flow-mediated vasodilation (FMD) and peripheral arterial tonometry (PAT)
timeFrame: 14 days after study drug treatment
measure: The difference of anti-inflammatory biomarkers
timeFrame: 14 days after study drug treatment
Other outcomes:
measure: Adverse events
timeFrame: 6 weeks
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.