Chronic Kidney Disease (CKD) Platelet Study

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Kidney Diseases, Heart Attack, Stroke, Ischemic

Intervention / Treatment
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* Drug: Ticagrelor 90mg
* Drug: Clopidogrel 75mg
* Drug: Aspirin 81 mg


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 91 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD-Ticagrelor<br>Ticagrelor 90 mg twice daily (double blind, random assignment) + aspirin 81 mg/d | Drug: Ticagrelor 90mg<br>* Ticagrelor Pill<br>* Other names: Brilinta;Drug: Aspirin 81 mg<br>* Aspirin Pill<br>* Other names: baby aspirin;|
| Active Comparator: CKD-Clopidogrel<br>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 | Drug: Clopidogrel 75mg<br>* Clopidogrel Pill and a matching placebo to conceal frequency<br>* Other names: Plavix;Drug: Aspirin 81 mg<br>* Aspirin Pill<br>* Other names: baby aspirin;|
| Active Comparator: Control-ticagrelor<br>Open label ticagrelor, 90 mg twice daily + aspirin 81 mg/d | Drug: Ticagrelor 90mg<br>* Ticagrelor Pill<br>* Other names: Brilinta;Drug: Aspirin 81 mg<br>* Aspirin Pill<br>* Other names: baby aspirin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Surface P-selectin Expression | Platelet surface P-selectin expression was measured using flow cytometry before and after treatment. | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P2Y12 inhibitors, Platelet aggregation, ticagrelor, clopidogrel, chronic kidney disease