ONSET and OFFSET of Ticagrelor in ESRD

• ClinicalTrials.gov Identifier: NCT02163954
• Recruitment Status: Completed
• First Posted: June 16, 2014
• Last Update Posted: June 16, 2014
• Sponsor: Kyunghee University Medical Center
• Collaborator: Kyunghee University
• Information provided by (Responsible Party): Weon Kim, Kyunghee University Medical Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease	Drug: Ticagrelor; Drug: Clopidogrel	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Investigator)
• Primary Purpose: Treatment
• Official Title: Platelet Reactivity in Patients With End Stage Renal Disease Receiving Clopidogrel Compared With Ticagrelor
• Study Start Date: January 2013
• Actual Primary Completion Date: August 2013
• Actual Study Completion Date: August 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Clopidogrel; Patients treated with clopidogrel for 14 days	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.; Other Name: Ticagrelor (Brilinta); Drug: 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.; Other Name: Clopidogrel (Plavix)
Experimental: Ticagrelor; Patients treated with ticagrelor for 14 days	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.; Other Name: Ticagrelor (Brilinta); Drug: 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.; Other Name: Clopidogrel (Plavix)

Outcome Measures

Primary Outcome Measures :

1. The difference of antiplatelet effects assessed by VerifyNow assay [ Time Frame: 14 days after study drug treatment ]
   The difference of PRU values achieved following antiplatelet therapy

Secondary Outcome Measures :

1. the rate of onset and offset of the antiplatelet effects [ Time Frame: 14 days after study drugs treatment ]
   the difference of slope during onset and offset of study drugs

Other Outcome Measures:

1. Adverse events [ Time Frame: during study period ]
   Adverse events such as bleeding

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

Korea, Republic of

Kyung Hee University Hospital

Seoul, Korea, Republic of, 130-702

Sponsors and Collaborators

Kyunghee University Medical Center

Kyunghee University

Investigators

• Principal Investigator: Weon Kim, MD, PhD; Kyung Hee University Hospital

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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:CD008834. doi: 10.1002/14651858.CD008834.pub4. Review.

• Responsible Party: Weon Kim, Professor, Kyunghee University Medical Center
• ClinicalTrials.gov Identifier: NCT02163954
• Other Study ID Numbers: PIANO3; Seoul, Korea ( Other Grant/Funding Number: 2010-0019913 )
• First Posted: June 16, 2014
• Last Update Posted: June 16, 2014
• Last Verified: June 2014

Keywords provided by Weon Kim, Kyunghee University Medical Center:

platelet; ticagrelor; clopidogrel; end stage renal disease; hemodialysis

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Urologic Diseases; Renal Insufficiency; Clopidogrel; Ticagrelor; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs