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

Primary Purpose

Sepsis, Acute Infection, Organ Failure

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Fisetin-dose 1
Fisetin-dose 2
Placebo
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sepsis

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Fisetin- dose 1

Fisetin- dose 2

Placebo

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Safety of 2 doses of fisetin in patients with mild sepsis
Outcome is the number of serious adverse event
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.
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.
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.
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.
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.
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.
Days in the ICU
This outcome is the number of days the patient was admitted to the ICU.
All-cause mortality
This outcome is the proportion of patients suffering all-cause mortality prior to day 28.
Peripheral CD3+ senescent (SnCs) immune cells
Outcome is the relative expression of p16Ink4a in CD3+ cells.
Outcome is the relative expression of p16Ink4a in CD3+ cells.
Outcome is the relative expression of p16Ink4a in CD3+ cells.
TNF-alpha
Outcome is the concentration of TNF-alpha by Luminex human discovery assay

Full Information

First Posted
February 24, 2023
Last Updated
August 23, 2023
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT05758246
Brief Title
Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
Official Title
Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 23, 2023 (Actual)
Primary Completion Date
August 23, 2026 (Anticipated)
Study Completion Date
August 23, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis, Acute Infection, Organ Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
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.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fisetin- dose 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Fisetin- dose 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Fisetin-dose 1
Intervention Description
20mg/kg once a day for one day.
Intervention Type
Drug
Intervention Name(s)
Fisetin-dose 2
Intervention Description
20mg/kg once a day for two days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo treatment
Primary Outcome Measure Information:
Title
Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA)
Description
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.
Time Frame
day 7
Secondary Outcome Measure Information:
Title
Safety of 2 doses of fisetin in patients with mild sepsis
Description
Outcome is the number of serious adverse event
Time Frame
day 28
Title
Organ failure free days
Description
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.
Time Frame
day 28
Title
Total SOFA score
Description
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.
Time Frame
day 7
Title
Zubrod performance status
Description
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.
Time Frame
day 7
Title
SF-12 score
Description
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.
Time Frame
day 7
Title
SF-12 score
Description
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.
Time Frame
day 28
Title
Zubrod performance status
Description
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.
Time Frame
day 28
Title
Days in the ICU
Description
This outcome is the number of days the patient was admitted to the ICU.
Time Frame
day 28
Title
All-cause mortality
Description
This outcome is the proportion of patients suffering all-cause mortality prior to day 28.
Time Frame
Day 28
Title
Peripheral CD3+ senescent (SnCs) immune cells
Description
Outcome is the relative expression of p16Ink4a in CD3+ cells.
Time Frame
day 7
Title
Outcome is the relative expression of p16Ink4a in CD3+ cells.
Description
Outcome is the relative expression of p16Ink4a in CD3+ cells.
Time Frame
day 28
Title
TNF-alpha
Description
Outcome is the concentration of TNF-alpha by Luminex human discovery assay
Time Frame
day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael Puskarich, MD
Phone
612 626 6911
Email
mike-em@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Puskarich, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

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

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