Clinical trial NCT05758246: Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
Official title: Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sepsis
Acute Infection
Organ Failure
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2023-03-07
Enrollment: 220
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA)
timeFrame: day 7
Secondary outcomes:
measure: Safety of 2 doses of fisetin in patients with mild sepsis
timeFrame: day 28
measure: Organ failure free days
timeFrame: day 28
measure: Total SOFA score
timeFrame: day 7
measure: Zubrod performance status
timeFrame: day 7
measure: SF-12 score
timeFrame: day 7
measure: SF-12 score
timeFrame: day 28
measure: Zubrod performance status
timeFrame: day 28
measure: Days in the ICU
timeFrame: day 28
measure: All-cause mortality
timeFrame: Day 28
measure: Peripheral CD3+ senescent (SnCs) immune cells
timeFrame: day 7
measure: Outcome is the relative expression of p16Ink4a in CD3+ cells.
timeFrame: day 28
measure: TNF-alpha
timeFrame: day 7
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Burnsville
country: United States
facility: Ridges
state: Minnesota
city: Edina
country: United States
facility: Southdale
state: Minnesota
city: Maplewood
country: United States
facility: M Health Fairview St. John's
state: Minnesota
city: Maplewood
country: United States
facility: St. John's
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Minneapolis
country: United States
facility: HCMC
state: Minnesota
city: Minneapolis
country: United States
facility: UMMC
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
Study officials:
affiliation: University of Minnesota
name: Michael Puskarich, MD
role: PRINCIPAL_INVESTIGATOR
References: