ONSET and OFFSET of Ticagrelor in ESRD

Chronic Kidney Disease Clinical Trial

Official title:

Platelet Reactivity in Patients With End Stage Renal Disease Receiving Clopidogrel Compared With Ticagrelor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02163954
• Other study ID #: PIANO3
• Secondary ID: Seoul, Korea
• Status: Completed
• Phase: Phase 3
• First received: June 12, 2014
• Last updated: June 12, 2014
• Start date: January 2013
• Est. completion date: August 2013

Study information

• Verified date: June 2014
• Source: Kyunghee University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Drug:
• Ticagrelor
After randomization, an initial loading dose of ticagrelor (180 mg) was given and maintenance doses (ticagrelor 90 mg twice daily) was treated for 14 days.
• Clopidogrel
After randomization, an initial loading dose of clopidogrel (300 mg) was given and maintenance doses (clopidogrel 75 mg once daily) was treated for 14 days.

Locations

Country	Name	City	State
Korea, Republic of	Kyung Hee University Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Kyunghee University Medical Center	Kyung Hee University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events	Adverse events such as bleeding	during study period	Yes
Primary	The difference of antiplatelet effects assessed by VerifyNow assay	The difference of PRU values achieved following antiplatelet therapy	14 days after study drug treatment	No
Secondary	the rate of onset and offset of the antiplatelet effects	the difference of slope during onset and offset of study drugs	14 days after study drugs treatment	No