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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Acute Infection; Organ Failure
• Intervention / Treatment: Drug: Placebo; Drug: Fisetin-dose 1; Drug: Fisetin-dose 2

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Michael Puskarich, MD; Phone Number: 612 626 6911; Email: mike-em@umn.edu

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • Recruiting
      • University of Florida
      • Contact: Faheem W Guirgis, MD; Phone Number: 352-265-5911; Email: fguirgis@ufl.edu
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Brett A Faine, PharmD; Phone Number: 319-310-8067; Email: brett-faine@uiowa.edu
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Recruiting
      • Ridges
      • Contact: Lauren Barrett; Email: barre998@umn.edu
    • Edina, Minnesota, United States, 55435
      • Recruiting
      • Southdale
      • Contact: Lauren Barrett; Email: barre998@umn.edu
    • Maplewood, Minnesota, United States, 55109
      • Recruiting
      • St. John's
      • Contact: Lauren Barrett; Email: barre998@umn.edu
    • Maplewood, Minnesota, United States, 55109
      • Recruiting
      • M Health Fairview St. John's
      • Contact: David Wacker, PhD
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Recruiting
      • HCMC
      • Contact: Audrey Hendrickson; Email: audrey.hendrickson@hcmed.org
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • UMMC
      • Contact: Lauryn Barrett; Email: barre998@umn.edu
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Recruiting
      • University of Mississippi Medical Center
      • Contact: James W Galbraith, MD; Phone Number: 601-984-5443; Email: jgalbraith@umc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Fisetin-dose 1; 20mg/kg once a day for one day.
Experimental: 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.	Drug: Fisetin-dose 2; 20mg/kg once a day for two days
Placebo Comparator: 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.	Drug: Placebo; Placebo treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA)	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.	day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of 2 doses of fisetin in patients with mild sepsis	Outcome is the number of serious adverse event	day 28
Organ failure free days	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.	day 28
Total SOFA score	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.	day 7
Zubrod performance status	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.	day 7
SF-12 score	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.	day 7
SF-12 score	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.	day 28
Zubrod performance status	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.	day 28
Days in the ICU	This outcome is the number of days the patient was admitted to the ICU.	day 28
All-cause mortality	This outcome is the proportion of patients suffering all-cause mortality prior to day 28.	Day 28
Peripheral CD3+ senescent (SnCs) immune cells	Outcome is the relative expression of p16Ink4a in CD3+ cells.	day 7
Outcome is the relative expression of p16Ink4a in CD3+ cells.	Outcome is the relative expression of p16Ink4a in CD3+ cells.	day 28
TNF-alpha	Outcome is the concentration of TNF-alpha by Luminex human discovery assay	day 7

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Michael Puskarich, MD, University of Minnesota

Publications and helpful links

General Publications

• Silva M, Wacker DA, Driver BE, Staugaitis A, Niedernhofer LJ, Schmidt EL, Kirkland JL, Tchkonia T, Evans T, Serrano CH, Ventz S, Koopmeiners JS, Puskarich MA; STOP-Sepsis Investigators. Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in elderly patients: Study protocol for a multicenter, randomized, adaptive allocation clinical trial. Trials. 2024 Oct 21;25(1):698. doi: 10.1186/s13063-024-08474-2.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2023
• Primary Completion (Estimated): August 23, 2026
• Study Completion (Estimated): August 23, 2026

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Estimated): October 15, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Sepsis
• Other Study ID Numbers: HRP-XXX

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No