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Genotype and Platelet Reactivity in Patients on Hemodialysis

Primary Purpose

Chronic Kidney Disease

Status
Unknown status
Phase
Phase 3
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Ticagrelor
Clopidogrel
Sponsored by
Kyunghee University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Kidney Disease focused on measuring platelet, ticagrelor, clopidogrel, end stage renal disease, hemodialysis, genetics

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kyung Hee University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Active Comparator

Active Comparator

Active Comparator

Active Comparator

Arm Label

Ticagrelor 180mg in ESRD patients

Clopidogrel 75mg in ESRD patients

Clopidogrel 150mg in ESRD patients

Ticagrelor 180mg in normal kidney

Clopidogrel 75mg in normal kidney

Arm Description

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.

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.

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.

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

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.

Outcomes

Primary Outcome Measures

The difference of antiplatelet effects according to genotype
The difference of P2Y12 reaction units (PRUs) according to genotype

Secondary Outcome Measures

The difference of antiplatelet effects according to kidney function
The difference of P2Y12 reaction units (PRUs) according to kidney function

Full Information

First Posted
March 14, 2015
Last Updated
March 19, 2015
Sponsor
Kyunghee University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02394145
Brief Title
Genotype and Platelet Reactivity in Patients on Hemodialysis
Official Title
The Relationship Between Genotype and Platelet Reactivity in Patients Treated With Ticagrelor Versus Clopidogrel: PIANO Genotype Study
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Unknown status
Study Start Date
September 2009 (undefined)
Primary Completion Date
August 2015 (Anticipated)
Study Completion Date
August 2015 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kyunghee University Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease
Keywords
platelet, ticagrelor, clopidogrel, end stage renal disease, hemodialysis, genetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ticagrelor 180mg in ESRD patients
Arm Type
Experimental
Arm Description
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.
Arm Title
Clopidogrel 75mg in ESRD patients
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Clopidogrel 150mg in ESRD patients
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Ticagrelor 180mg in normal kidney
Arm Type
Active Comparator
Arm Description
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
Arm Title
Clopidogrel 75mg in normal kidney
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Ticagrelor
Other Intervention Name(s)
Brilinta
Intervention Description
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
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
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.
Primary Outcome Measure Information:
Title
The difference of antiplatelet effects according to genotype
Description
The difference of P2Y12 reaction units (PRUs) according to genotype
Time Frame
14 days after study drug treatment
Secondary Outcome Measure Information:
Title
The difference of antiplatelet effects according to kidney function
Description
The difference of P2Y12 reaction units (PRUs) according to kidney function
Time Frame
14 days after study drug treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Weon Kim, MD, PhD
Phone
82-2-958-8170
Email
mylovekw@hanmail.net
First Name & Middle Initial & Last Name or Official Title & Degree
Jong Shin Woo, MD, PhD
Phone
82-2-958-8176
Email
snowball77@hanmail.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Weon Kim, MD, PhD
Organizational Affiliation
Kyung Hee University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kyung Hee University Hospital
City
Seoul
ZIP/Postal Code
130-872
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Weon Kim, MD, PhD
Phone
2-958-8170
Ext
82
Email
mylovekw@hanmail.net
First Name & Middle Initial & Last Name & Degree
Jong Shin Woo, MD
Phone
2-958-8176
Ext
82
Email
snowball77@hanmail.net
First Name & Middle Initial & Last Name & Degree
Jong Shin Woo, MD

12. IPD Sharing Statement

Citations:
PubMed Identifier
35224730
Citation
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.
Results Reference
derived

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Genotype and Platelet Reactivity in Patients on Hemodialysis

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