Ticagrelor for Inflammation and Cardiovascular Risk in Patients With Chronic Kidney Disease

Korábbi kezelés

• Acute coronary syndrome, acute myocardial infarction, or acute cerebrovascular event within 6 months prior to screening. Rationale: these participants are likely receiving P2Y12 inhibitor therapy, and their enrollment would confound the primary endpoint.
• Hospitalization, major surgery, or use of systemic antibiotics within 1 month prior to screening. Rationale: these events are potentially associated with acute inflammatory changes that would confound baseline cytokine measurements.
• History of gastrointestinal bleeding within 6 months prior to screening.
• Concomitant use of any antiplatelet agent other than aspirin (e.g., clopidogrel, prasugrel, dipyridamole) or any antithrombotic or anticoagulant medication (e.g., warfarin, direct oral anticoagulants) at the time of screening or anticipated need during the study period.
• Treatment with another investigational drug or other intervention ongoing, or within a month of randomization.

Más betegség

• Blood dyscrasias, active bleeding of any site, or a known bleeding diathesis.
• Any active malignancy requiring systemic treatment, or chronic liver disease (including cirrhosis or hepatitis with active inflammation).
• Known severe hypersensitivity or allergy to ticagrelor or any component of the study drug formulation.
• Ongoing treatment for infection.
  • Population 2: Control Participants
• Current use of antibiotics or ongoing infection.

Laborértékek

• End-stage renal disease (defined as receiving peritoneal dialysis or hemodialysis) or any prior solid organ or bone marrow transplant. Rationale: dialysis directly affects platelet function and would confound the primary endpoint.
• Hemoglobin \<8 g/dL, white blood cell count \>20,000/μL, or platelet count \<50,000/μL at the time of screening.
• Current use of immunosuppressive medications (e.g., corticosteroids, calcineurin inhibitors, mycophenolate). Rationale: these medications independently alter cytokine profiles and leukocyte gene expression, confounding the primary and mechanistic endpoints.
• Any known diagnosis of chronic kidney disease, eGFR ≤60 ml/min/1.73m², or UACR ≥30 mg/g.

Életkor

• Age older than 75 years. Rationale: individuals older than 75 years carry a substantially higher risk of bleeding on antiplatelet therapy and are excluded for participant safety.

Egyéb

• Population 1: CKD Participants
• Unwilling or unable to participate in the protocol or comply with its components.
• Acute kidney injury superimposed on CKD at the time of screening.
• Pregnancy or breastfeeding at the time of screening or plans to become pregnant during the study period. Women of reproductive potential will undergo a urine pregnancy test at screening (Visit 1); a positive result excludes from participation.
• Inability to sign consent and HIPAA form. Legal Authorized Representatives are not allowed to sign the consent form.
• Unwillingness or inability to participate in the protocol or comply with any of its components.
• Any current use of aspirin or NSAIDs and not willing to hold.

• Population 1: CKD Participants
• Provision of signed and dated written informed consent.
• Age 21 to 75 years at the time of screening, inclusive.
• Diagnosis of chronic kidney disease with estimated glomerular filtration rate (eGFR) \<45 ml/min/1.73m² as calculated by the CKD-EPI equation, confirmed from medical records or laboratory results.
• Currently receiving the maximally tolerated or labeled dose of a renin-angiotensin-aldosterone system inhibitor (RAASi) as guideline-directed medical therapy (GDMT), or documentation of the reason for not receiving RAASi (e.g., intolerance, contraindication).
  • Population 2: Control Participants
• Provision of signed and dated written informed consent.
• Age 21 to 75 years at the time of screening, inclusive.
• Normal kidney function, defined as eGFR \>60 ml/min/1.73m² (CKD-EPI equation) and urinary albumin-to-creatinine ratio (UACR) \<30 mg/g, confirmed from medical records or laboratory results.