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

NCT ID: NCT05758246

Last Updated: 2025-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-23

Study Completion Date

2026-08-23

Brief Summary

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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

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Conditions

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Sepsis Acute Infection Organ Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Fisetin-dose 1

Intervention Type DRUG

20mg/kg once a day for one day.

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.

Group Type EXPERIMENTAL

Fisetin-dose 2

Intervention Type DRUG

20mg/kg once a day for two days

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.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo treatment

Interventions

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Fisetin-dose 1

20mg/kg once a day for one day.

Intervention Type DRUG

Fisetin-dose 2

20mg/kg once a day for two days

Intervention Type DRUG

Placebo

Placebo treatment

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Puskarich, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

Ridges

Burnsville, Minnesota, United States

Site Status RECRUITING

Southdale

Edina, Minnesota, United States

Site Status RECRUITING

M Health Fairview St. John's

Maplewood, Minnesota, United States

Site Status RECRUITING

St. John's

Maplewood, Minnesota, United States

Site Status RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

HCMC

Minneapolis, Minnesota, United States

Site Status RECRUITING

UMMC

Minneapolis, Minnesota, United States

Site Status RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Michael Puskarich, MD

Role: CONTACT

612 626 6911

Facility Contacts

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Faheem W Guirgis, MD

Role: primary

352-265-5911

Brett A Faine, PharmD

Role: primary

319-310-8067

Lauren Barrett

Role: primary

Lauren Barrett

Role: primary

David Wacker, PhD

Role: primary

Lauren Barrett

Role: primary

Audrey Hendrickson

Role: primary

Lauryn Barrett

Role: primary

James W Galbraith, MD

Role: primary

601-984-5443

References

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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.

Reference Type DERIVED
PMID: 39434114 (View on PubMed)

Other Identifiers

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HRP-XXX

Identifier Type: -

Identifier Source: org_study_id

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