Overview
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
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
