Chronic Kidney Disease (CKD) Platelet Study
Condition: Chronic Kidney Diseases; Heart Attack; Stroke, Ischemic
MeSH terms: Ischemic Stroke; Kidney Diseases; Renal Insufficiency, Chronic; Myocardial Infarction
Intervention: Ticagrelor 90mg; Clopidogrel 75mg; Aspirin 81 mg
Intervention description: Ticagrelor Pill; Clopidogrel Pill and a matching placebo to conceal frequency; Aspirin Pill
Intervention MeSH terms: Aspirin; Clopidogrel; Ticagrelor
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Investigator, Outcomes 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.
Enrollment: 76.0
Sex: All
Minimum age: 18 Years
Maximum age: 91 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: P2Y12 inhibitors; Platelet aggregation; ticagrelor; clopidogrel; chronic kidney disease

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Males and females, aged 18-91 years

          2. Ability to understand and sign informed consent after the nature of the study has been
             fully explained

          3. 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

          4. 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.