Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
Trial Parameters
Brief Summary
The long-term goal is to test the clinical efficacy of senolytic therapies to reduce progression to and severity of sepsis in older patients. The central hypothesis is that a threshold burden of SnCs predisposes to a SASP mediated dysfunctional response to PAMPs, contributing to a disproportionate burden of sepsis in older patients. The study hypothesizes timely treatment with fisetin will interrupt this pathway. A multicenter, randomized, adaptive allocation clinical trial to identify the most efficacious dose of the senolytic fisetin to reduce the composite cardiovascular, respiratory, and renal sequential organ failure assessment score at 1 week, and predict the probability of success of a definitive phase III clinical trial.
Eligibility Criteria
Inclusion Criteria: * Age \>=65 years * Primary diagnosis of acute infection (per investigator judgment) * SOFA \>1 * Admission order to the hospital * Expected length of stay \>=48 hours (per investigator judgment) Exclusion Criteria: * Admission to the ICU * Vasopressors, mechanical ventilation, or dialysis * Comfort care only * Total bilirubin \>3X or AST/ALT \>4x upper limit of normal * eGFR \< 25 ml/ min/ 1.73 m2 * Hemoglobin \<7 g/dL; white blood cell count ≤ 2,000/mm3; absolute neutrophil count ≤1 x 10\^9/;, or platelet count ≤ 40,000/μL * Known HIV, Hepatitis B, or Hepatitis C * Invasive fungal infection (per investigator judgment) * Uncontrolled effusions or ascites (per investigator judgment) * New/active invasive cancer except non-melanoma skin cancers * Known hypersensitivity or allergy to Fisetin. * Active treatment with potential drug-drug interactions * Enrolled in another sepsis clinical trial