Genotype and Platelet Reactivity in Patients on Hemodialysis

NCT ID: NCT02394145

Last Updated: 2015-03-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-09-30
• Study Completion Date: 2015-08-31

Brief 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.

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. 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.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ticagrelor 180mg in ESRD patients

After randomization, ESRD patients on HD will be treated by an initial loading dose of ticagrelor (180 mg) and maintenance doses (ticagrelor 90 mg twice daily) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Group Type: EXPERIMENTAL

Ticagrelor

Intervention Type: DRUG

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 75mg in ESRD patients

After randomization, ESRD patients on HD will be treated by an initial loading dose of clopidogrel 300 mg) and maintenance doses (clopidogrel 75 mg once a day) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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.

Clopidogrel 150mg in ESRD patients

After randomization, ESRD patients on HD will be treated by an initial loading dose of clopidogrel 300 mg) and maintenance doses (clopidogrel 150 mg once a day) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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.

Ticagrelor 180mg in normal kidney

After randomization, patients with normal kidney function will be treated by an initial loading dose of ticagrelor (180 mg) and maintenance doses (ticagrelor 90 mg twice daily) for 14 days. Platelet reactivity and genetic polymorphism will be assessed

Group Type: ACTIVE_COMPARATOR

Ticagrelor

Intervention Type: DRUG

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 75mg in normal kidney

After randomization, patients with normal kidney function will be treated by an initial loading dose of clopidogrel 300 mg) and maintenance doses (clopidogrel 75 mg once a day) for 14 days. Platelet reactivity and genetic polymorphism will be assessed.

Group Type: ACTIVE_COMPARATOR

Clopidogrel

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Brilinta; Plavix

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyunghee University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Weon Kim

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weon Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kyung Hee University Hospital

Locations

Kyung Hee University Hospital

Seoul, Seoul, South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Weon Kim, MD, PhD

Role: CONTACT

mylovekw@hanmail.net

82-2-958-8170

Jong Shin Woo, MD, PhD

Role: CONTACT

snowball77@hanmail.net

82-2-958-8176

Facility Contacts

Weon Kim, MD, PhD

Role: primary

mylovekw@hanmail.net

2-958-8170 ext. 82

Jong Shin Woo, MD

Role: backup

snowball77@hanmail.net

2-958-8176 ext. 82

References

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(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

Reference Type: DERIVED

PMID: 35224730 (View on PubMed)

Other Identifiers

PIANO-genetics

Identifier Type: -

Identifier Source: org_study_id