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Chronic Kidney Disease (CKD) Platelet Study

Primary Purpose

Chronic Kidney Diseases, Heart Attack, Stroke, Ischemic

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

Ticagrelor 90mg

Clopidogrel 75mg

Aspirin 81 mg

About this trial

This is an interventional treatment trial for Chronic Kidney Diseases focused on measuring P2Y12 inhibitors, Platelet aggregation, ticagrelor, clopidogrel, chronic kidney disease

Eligibility Criteria

18 Years - 91 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Males and females, aged 18-91 years
Ability to understand and sign informed consent after the nature of the study has been fully explained
CKD participants: Non-dialysis CKD patients: Presence of CKD with an estimated GFR of <30 mL/min/1.73 m2 for a period of ≥3 months, as defined by the National Kidney Foundation (NKF) and determined with the CKD-EPI creatinine-based formula
Controls with normal kidney function: participants with an estimated GFR >90 mL/min/1.73 m2 as determined by the CKD-EPI creatinine-based formula and a urine albumin-to-creatinine ratio <30 mg/g as defined by the National Kidney Foundation

Exclusion Criteria:

No healthcare power of attorney to sign informed consent
Unwillingness or inability to participate in the protocol or comply with any of its components.
Subjects unable or unwilling to stop taking:
- Aspirin and other antithrombotic agents, like cilostazol, ranolazine, aggrenox, prasugrel, warfarin, xarelto, pradaxa, eliquis.
- Glycoprotein IIb/IIIa antagonist (abciximab-ReoPro, eptifibatide-Integrilin, tirofiban-Aggrastal)
- NSAIDs and PPIs
- Fish oil, Vitamin E and herbal supplements
Acute kidney injury superimposed on CKD
Kidney transplant or any other solid organ transplant recipient
End-stage kidney disease on maintenance dialysis (peritoneal or hemodialysis)
Nephrotic syndrome defined as nephrotic range proteinuria, hypoalbuminemia, hyperlipidemia and generalized edema
Recent hospitalization or surgery <3 months
Acute coronary or cerebrovascular event in the last 12 months
Blood dyscrasias, active bleeding, or bleeding diathesis
Gastrointestinal bleeding in the last 6 months
Recent treatment (<30 days) with a glycoprotein IIb/IIIa antagonist (Integrelin).
Hematocrit <25%, white blood cell count >20,000/μL, or platelet count <50,000/μL
Any active malignancy or liver disease.
Pregnancy
Positive urine pregnancy test in a woman of childbearing potential prior to study entry. A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
Patients must not be nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Sites / Locations

Central Arkansas Veterans Affairs Hospital
University of Arkansas for Medical Sciences

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

CKD-Ticagrelor

CKD-Clopidogrel

Control-ticagrelor

Arm Description

Ticagrelor 90 mg twice daily (double blind, random assignment) + aspirin 81 mg/d

Clopidogrel 75 mg/day in the morning and a matching placebo in the evening to conceal frequency (double blind, random assignment) + aspirin 81 mg/d

Open label ticagrelor, 90 mg twice daily + aspirin 81 mg/d

Outcomes

Primary Outcome Measures

ADP Induced Platelet Aggregation

We will use summary statistics to describe the distribution of the data. Post-treatment ADP-induced WBPA value in ohms (Ω) will be the primary outcome variable. We will use an analysis of covariance (ANCOVA) model to compare the treatment effects of ticagrelor vs. clopidogrel in CKD patients because this approach has higher statistical power than other methods to analyze drug effects. T

Secondary Outcome Measures

Platelet Surface P-selectin Expression

Platelet surface P-selectin expression was measured using flow cytometry before and after treatment.

Full Information

NCT ID

NCT03649711

First Posted

August 21, 2018

Last Updated

December 8, 2022

Sponsor

University of Arkansas

Collaborators

American Society of Nephrology

1. Study Identification

Unique Protocol Identification Number

NCT03649711

Brief Title

Chronic Kidney Disease (CKD) Platelet Study

Official Title

A Mechanistic Study in Patients With Non-Dialysis Chronic Kidney Disease to Investigate Altered Platelet Response to Antiplatelet Therapy (CKD-Platelet Study)

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

November 1, 2018 (Actual)

Primary Completion Date

September 2, 2021 (Actual)

Study Completion Date

September 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Arkansas

Collaborators

American Society of Nephrology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

Brief Summary

This study evaluates how aspirin, clopidogrel and ticagrelor work in people with chronic kidney disease (CKD) compared to people with normal kidneys. In the first part of the study, half of CKD participants will be randomly assigned to ticagrelor and aspirin, while the other half will be assigned to clopidogrel and aspirin in a blinded fashion. The treatment duration will be two weeks. After recruiting CKD participants the investigator will recruit controls with normal kidney function that will receive only ticagrelor and aspirin for two weeks.

Detailed Description

It is known that people with chronic kidney disease (CKD) are at higher risk to have heart and blood vessel problems like heart attack and stroke compared to people that do not have kidney problems. Aspirin, clopidogrel and ticagrelor prevent blood clots building up in the vessels. If a blood clot is present in one vessel, it could stop oxygen carrying blood to get to a specific organ, and that could cause problems like heart attack or stroke. There is very little knowledge about the way this group of medicines works in people with chronic kidney disease as well as it works in individuals with normal kidney function.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Kidney Diseases, Heart Attack, Stroke, Ischemic

Keywords

P2Y12 inhibitors, Platelet aggregation, ticagrelor, clopidogrel, chronic kidney disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

CKD participants will be double-blind randomized in these two arms: Arm 1 - Ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) + Aspirin 81 mg/day. Ticagrelor is the test treatment. Arm 2 - Clopidogrel, 75 mg/day in the morning and a matching placebo in the evening + Aspirin 81 mg/day. Clopidogrel is the reference treatment. Arm 3: Control with normal kidney function will be recruited after matching for age and diabetes status to the Arm 1 participants. Participants will be asked to take Ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) and aspirin 81 mg/day. Open label treatment. All participants are required to take the oral treatment for a total of two weeks.

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

CKD participants will be randomly assigned into one of the 2 study groups: ticagrelor (90 mg) one pill in the morning and one pill in the evening, or, clopidogrel (75 mg) one pill in the morning + placebo one pill in the evening. Placebo looks like the study drug but has no medicine in it. Neither participant nor the study personnel will know about allocation. The study drugs will look the same, except aspirin pill which will be dispensed to everyone in an open label manner. There is no masking for control with normal kidney function. Participants will be asked to take open label ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) and aspirin 81 mg/day.

Allocation

Randomized

Enrollment

76 (Actual)

8. Arms, Groups, and Interventions

Arm Title

CKD-Ticagrelor

Arm Type

Experimental

Arm Description

Ticagrelor 90 mg twice daily (double blind, random assignment) + aspirin 81 mg/d

Arm Title

CKD-Clopidogrel

Arm Type

Active Comparator

Arm Description

Clopidogrel 75 mg/day in the morning and a matching placebo in the evening to conceal frequency (double blind, random assignment) + aspirin 81 mg/d

Arm Title

Control-ticagrelor

Arm Type

Active Comparator

Arm Description

Open label ticagrelor, 90 mg twice daily + aspirin 81 mg/d

Intervention Type

Drug

Intervention Name(s)

Ticagrelor 90mg

Other Intervention Name(s)

Brilinta

Intervention Description

Ticagrelor Pill

Intervention Type

Drug

Intervention Name(s)

Clopidogrel 75mg

Other Intervention Name(s)

Plavix

Intervention Description

Clopidogrel Pill and a matching placebo to conceal frequency

Intervention Type

Drug

Intervention Name(s)

Aspirin 81 mg

Other Intervention Name(s)

baby aspirin

Intervention Description

Aspirin Pill

Primary Outcome Measure Information:

Title

ADP Induced Platelet Aggregation

Description

Time Frame

2 weeks

Secondary Outcome Measure Information:

Title

Platelet Surface P-selectin Expression

Description

Platelet surface P-selectin expression was measured using flow cytometry before and after treatment.

Time Frame

2 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

91 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Males and females, aged 18-91 years Ability to understand and sign informed consent after the nature of the study has been fully explained CKD participants: Non-dialysis CKD patients: Presence of CKD with an estimated GFR of <30 mL/min/1.73 m2 for a period of ≥3 months, as defined by the National Kidney Foundation (NKF) and determined with the CKD-EPI creatinine-based formula Controls with normal kidney function: participants with an estimated GFR >90 mL/min/1.73 m2 as determined by the CKD-EPI creatinine-based formula and a urine albumin-to-creatinine ratio <30 mg/g as defined by the National Kidney Foundation Exclusion Criteria: No healthcare power of attorney to sign informed consent Unwillingness or inability to participate in the protocol or comply with any of its components. Subjects unable or unwilling to stop taking: Aspirin and other antithrombotic agents, like cilostazol, ranolazine, aggrenox, prasugrel, warfarin, xarelto, pradaxa, eliquis. Glycoprotein IIb/IIIa antagonist (abciximab-ReoPro, eptifibatide-Integrilin, tirofiban-Aggrastal) NSAIDs and PPIs Fish oil, Vitamin E and herbal supplements Acute kidney injury superimposed on CKD Kidney transplant or any other solid organ transplant recipient End-stage kidney disease on maintenance dialysis (peritoneal or hemodialysis) Nephrotic syndrome defined as nephrotic range proteinuria, hypoalbuminemia, hyperlipidemia and generalized edema Recent hospitalization or surgery <3 months Acute coronary or cerebrovascular event in the last 12 months Blood dyscrasias, active bleeding, or bleeding diathesis Gastrointestinal bleeding in the last 6 months Recent treatment (<30 days) with a glycoprotein IIb/IIIa antagonist (Integrelin). Hematocrit <25%, white blood cell count >20,000/μL, or platelet count <50,000/μL Any active malignancy or liver disease. Pregnancy Positive urine pregnancy test in a woman of childbearing potential prior to study entry. A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Patients must not be nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jain Nishank, MD

Organizational Affiliation

University of Arkansas for Medical

Official's Role

Principal Investigator

Facility Information:

Facility Name

Central Arkansas Veterans Affairs Hospital

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

Facility Name

University of Arkansas for Medical Sciences

City

Little Rock

State/Province

Arkansas

ZIP/Postal Code

72205

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified data for all primary and secondary outcome measures will be uploaded on clinicaltrials.gov website.

IPD Sharing Time Frame

2 years after study closure indefinitely

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

Links:

URL

https://kidney360.asnjournals.org/content/early/2022/10/26/KID.0005532022

Description

publication

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Chronic Kidney Disease (CKD) Platelet Study

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