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

NCT05758246 | Recruiting Phase 2 FDA Drug

• 1 other identifier: HRP-XXX
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 10

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.

Conditions

Sepsis; Acute Infection; Organ Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (12)

• Safety of 2 doses of fisetin in patients with mild sepsis

  day 28

• Organ failure free days

  day 28

• Total SOFA score

  day 7

• Zubrod performance status

  day 7

• SF-12 score

  day 7

Study Arms (3)

Fisetin- dose 1

EXPERIMENTAL

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

Fisetin- dose 2

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Fisetin-dose 1 DRUG

20mg/kg once a day for one day.

Fisetin- dose 1

Fisetin-dose 2 DRUG

20mg/kg once a day for two days

Fisetin- dose 2

Placebo DRUG

Placebo treatment

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (10)

University of Florida

Gainesville, Florida, 32608, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Ridges

Burnsville, Minnesota, 55337, United States

RECRUITING

Southdale

Edina, Minnesota, 55435, United States

RECRUITING

M Health Fairview St. John's

Maplewood, Minnesota, 55109, United States

RECRUITING

St. John's

Maplewood, Minnesota, 55109, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55414, United States

RECRUITING

HCMC

Minneapolis, Minnesota, 55415, United States

RECRUITING

UMMC

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 39434114 DERIVED

MeSH Terms

Conditions

Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Michael Puskarich, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael Puskarich, MD

CONTACT

612 626 6911; mike-em@umn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants will initially be equally randomized between placebo, 20 mg/kg (once), and 20 mg/kg (once daily for 2 days). After 60 participants have been enrolled, the randomization ratio will be adapted so that a higher proportion of participants will be randomized to the optimal dosing regimen. The proportion randomized to the control will be held constant throughout the trial.

Study Record Dates

• First Submitted: February 24, 2023
• First Posted: March 7, 2023
• Study Start: August 23, 2023
• Primary Completion (Estimated): August 23, 2026
• Study Completion (Estimated): August 23, 2026
• Last Updated: October 15, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)