Genotype and Platelet Reactivity in Patients on Hemodialysis

Chronic Kidney Disease Clinical Trial

Official title:

The Relationship Between Genotype and Platelet Reactivity in Patients Treated With Ticagrelor Versus Clopidogrel: PIANO Genotype Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02394145
• Other study ID #: PIANO-genetics
• Status: Recruiting
• Phase: Phase 3
• First received: March 14, 2015
• Last updated: March 19, 2015
• Start date: September 2009
• 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

Patients with end stage renal disease (ESRD) on hemodialysis (HD) exhibited higher platelet reactivity to clopidogrel than did those with normal renal function. We 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 genetic influence in high platelet reactivity in patients with ESRD 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. We recently reported platelet inhibition by ticagrelor was markedly greater than by clopidogrel in patients with ESRD on HD. But exact mechanism of high platelet reactivity in ESRD patients was not fully evaluated. A possible postulation would be genetic influence. To investigate this issue, we will evaluate genetic polymorphism in patients with normal kidney function and ESRD on HD according to different doses of clopidogrel and ticagrelor. Genetic test will be assessed polymorphism of ABCB1, PON1, CYP2C19, CYP2C9 and P2Y12.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: August 2015
• Est. primary completion date: August 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

• Matching patients with normal kidney function

• documented coronary artery disease or high risk (Framingham heart risk score = 20%) of coronary artery disease

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: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ticagrelor
Patients with normal kidney function and ESRD on hemodialysis will be treated by ticagrelor 90mg twice a day for 14 days. After then, platelet reactivity will be assessed by light aggregometry and VerifyNow assay.
• Clopidogrel
Patients with normal kidney function and ESRD on hemodialysis will be treated by clopidogrel 75mg or 150mg once a day for 14 days. After then, platelet reactivity will be assessed by light aggregometry and VerifyNow assay.

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
Primary	The difference of antiplatelet effects according to genotype	The difference of P2Y12 reaction units (PRUs) according to genotype	14 days after study drug treatment	Yes
Secondary	The difference of antiplatelet effects according to kidney function	The difference of P2Y12 reaction units (PRUs) according to kidney function	14 days after study drug treatment	Yes