Ticagrelor and Anti-inflammatory Effects

Chronic Kidney Disease Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02406911
• Other study ID #: PIANO6
• Status: Recruiting
• Phase: Phase 3
• First received: March 14, 2015
• Last updated: March 30, 2015
• Start date: February 2015
• Est. completion date: August 2015

Study information

• Verified date: March 2015
• Source: Kyunghee University Medical Center
• Contact: Weon Kim, MD, PhD
• Phone: 82-2-958-8170
• Email: mylovekw[@]hanmail.net
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: August 2015
• Est. primary completion date: June 2015
• 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, each group will be treated as assigned dose of ticagrelor (ticagrelor 90mg once a day or 90mg twice a day) for 14 days. After 1 week wash-out period, cross-over study will be performed

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Kyunghee University Medical Center

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	6 weeks	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	Yes
Secondary	The difference of antiplatelet effects assessed by light aggregometry assay	The difference of IPA values achieved following antiplatelet therapy	14 days after study drug treatment	Yes
Secondary	The difference of endothelial function assessed by forearm flow-mediated vasodilation (FMD) and peripheral arterial tonometry (PAT)	The difference of endothelial functions achieved following antiplatelet therapy	14 days after study drug treatment	Yes
Secondary	The difference of anti-inflammatory biomarkers	The difference of hsCRP, CD40, P-selectin, and IL-6	14 days after study drug treatment	Yes