Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial

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.

Inclusion Criteria:Age >=65 yearsPrimary diagnosis of acute infection (per investigator judgment)SOFA >1Admission order to the hospitalExpected length of stay >=48 hours (per investigator judgment)Exclusion Criteria:Admission to the ICUVasopressors, mechanical ventilation, or dialysisComfort care onlyTotal bilirubin >3X or AST/ALT >4x upper limit of normaleGFR < 25 ml/ min/ 1.73 m2Hemoglobin <7 g/dL; white blood cell count ≤ 2,000/mm3; absolute neutrophil count ≤1 x 10^9/;, or platelet count ≤ 40,000/μLKnown HIV, Hepatitis B, or Hepatitis CInvasive fungal infection (per investigator judgment)Uncontrolled effusions or ascites (per investigator judgment)New/active invasive cancer except non-melanoma skin cancersKnown hypersensitivity or allergy to Fisetin.Active treatment with potential drug-drug interactionsEnrolled in another sepsis clinical trial