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Ticagrelor and Anti-inflammatory Effects

Phase 3
Conditions
Chronic Kidney Disease
Interventions
Registration Number
NCT02406911
Lead Sponsor
Kyunghee University Medical Center
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
25
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Ticagrelor 180 mgTicagrelorAfter randomization, an initial loading dose of ticagrelor (180 mg) was given and usual dose ticagrelor (ticagrelor 90 mg twice a day) was treated for 14 days.
Ticagrelor 90 mgTicagrelorAfter randomization, an initial loading dose of ticagrelor (180 mg) was given and low dose ticagrelor (ticagrelor 90 mg once a day) was treated for 14 days.
Primary Outcome Measures
NameTimeMethod
The difference of antiplatelet effects assessed by VerifyNow assay14 days after study drug treatment

The difference of PRU values achieved following antiplatelet therapy

Secondary Outcome Measures
NameTimeMethod
The difference of antiplatelet effects assessed by light aggregometry assay14 days after study drug treatment

The difference of IPA values achieved following antiplatelet therapy

The difference of endothelial function assessed by forearm flow-mediated vasodilation (FMD) and peripheral arterial tonometry (PAT)14 days after study drug treatment

The difference of endothelial functions achieved following antiplatelet therapy

The difference of anti-inflammatory biomarkers14 days after study drug treatment

The difference of hsCRP, CD40, P-selectin, and IL-6

Trial Locations

Locations (1)

Kyung Hee University Hospital

🇰🇷

Seoul, Korea, Republic of

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