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

Sepsis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05758246
• Other study ID #: HRP-XXX
• Status: Recruiting
• Phase: Phase 2
• Start date: August 23, 2023
• Est. completion date: August 23, 2026

Study information

• Verified date: April 2024
• Source: University of Minnesota
• Contact: Michael Puskarich, MD
• Phone: 612 626 6911
• Email: mike-em[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: August 23, 2026
• Est. primary completion date: August 23, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Infection
• Organ Failure
• Sepsis
• Toxemia

Intervention

Drug:
• Fisetin-dose 1
20mg/kg once a day for one day.
• Fisetin-dose 2
20mg/kg once a day for two days
• Placebo
Placebo treatment

Locations

Country	Name	City	State
United States	Ridges	Burnsville	Minnesota
United States	Southdale	Edina	Minnesota
United States	St. John's	Maplewood	Minnesota
United States	HCMC	Minneapolis	Minnesota
United States	UMMC	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Safety of 2 doses of fisetin in patients with mild sepsis	Outcome is the number of serious adverse event	day 28
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Days in the ICU	This outcome is the number of days the patient was admitted to the ICU.	day 28
Secondary	All-cause mortality	This outcome is the proportion of patients suffering all-cause mortality prior to day 28.	Day 28
Secondary	Peripheral CD3+ senescent (SnCs) immune cells	Outcome is the relative expression of p16Ink4a in CD3+ cells.	day 7
Secondary	Outcome is the relative expression of p16Ink4a in CD3+ cells.	Outcome is the relative expression of p16Ink4a in CD3+ cells.	day 28
Secondary	TNF-alpha	Outcome is the concentration of TNF-alpha by Luminex human discovery assay	day 7