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

Phase 2

Recruiting

• Conditions: Acute Infection; Organ Failure; Sepsis
• Interventions: Drug: Fisetin-dose 1; Drug: Placebo; Drug: Fisetin-dose 2

• Registration Number: NCT05758246
• Lead Sponsor: University of Minnesota

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-24
• Study First Submitted QC: 2023-02-24
• Study First Posted: 2023-03-07
• Study Start: 2023-08-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-01-31
• Primary Completion: 2026-08-23
• Study Completion: 2026-08-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fisetin- dose 1	Fisetin-dose 1	Elderly (\>=65 years) patients admitted to the hospital with an acute infection and sequential organ failure assessment score sufficient for a diagnosis of sepsis, will be given the first dose of fisetin.
Placebo	Placebo	Elderly (\>=65 years) patients admitted to the hospital with an acute infection and sequential organ failure assessment score sufficient for a diagnosis of sepsis will receive placebo treatment.
Fisetin- dose 2	Fisetin-dose 2	Elderly (\>=65 years) patients admitted to the hospital with an acute infection and sequential organ failure assessment score sufficient for a diagnosis of sepsis, will be given the 2nd does of fisetin.

Primary Outcome Measures

Name	Time	Method
Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA)	day 7	The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body (neurologic, blood, liver, kidney, and blood pressure/hemodynamics) and assigns a score based on the data obtained in each category. This outcome assesses only the cardiovascular, respiratory, and renal categories of the total SOFA score, and calculates the change from day 0 to day 7.

Secondary Outcome Measures

Name	Time	Method
Total SOFA score	day 7	The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body (neurologic, blood, liver, kidney, and blood pressure/hemodynamics) and assigns a score based on the data obtained in each category.
Safety of 2 doses of fisetin in patients with mild sepsis	day 28	Outcome is the number of serious adverse event
Days in the ICU	day 28	This outcome is the number of days the patient was admitted to the ICU.
Organ failure free days	day 28	Outcome is 28 days minus the last day the patient required any of the following: ventilator support, vasopressors, or dialysis / renal replacement therapy. Patients who die prior to day 28 are given a value of -1.
Zubrod performance status	day 28	A scale for indicating a patient's functional level: 0 asymptomatic - 1 Symptomatic, fully ambulatory - 2 Symptomatic, in bed - 50% of the day - 3 Symptomatic, in bed; 50% of the day but not bedridden - 4 Bedridden - 5 Dead.
SF-12 score	day 28	The SF-12 is a self-reported validated outcome measure assessing the impact of health on an individual 39;s everyday life. Patients fill out a 12 question survey which is then scored by a clinician or researcher.
All-cause mortality	Day 28	This outcome is the proportion of patients suffering all-cause mortality prior to day 28.
Peripheral CD3+ senescent (SnCs) immune cells	day 7	Outcome is the relative expression of p16Ink4a in CD3+ cells.
TNF-alpha	day 7	Outcome is the concentration of TNF-alpha by Luminex human discovery assay
Outcome is the relative expression of p16Ink4a in CD3+ cells.	day 28	Outcome is the relative expression of p16Ink4a in CD3+ cells.

Trial Locations

Locations (10)

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of Iowa; 🇺🇸 Iowa City, Iowa, United States

University of Mississippi Medical Center; 🇺🇸 Jackson, Mississippi, United States

Ridges; 🇺🇸 Burnsville, Minnesota, United States

Southdale; 🇺🇸 Edina, Minnesota, United States

M Health Fairview St. John's; 🇺🇸 Maplewood, Minnesota, United States

St. John's; 🇺🇸 Maplewood, Minnesota, United States

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States

HCMC; 🇺🇸 Minneapolis, Minnesota, United States

UMMC; 🇺🇸 Minneapolis, Minnesota, United States