Senolytics To slOw Progression of Sepsis (STOP-Sepsis) Trial
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Fisetin-dose 1
20mg/kg once a day for one day.
|
| Experimental: 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. |
Drug: Fisetin-dose 2
20mg/kg once a day for two days
|
| Placebo Comparator: 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. |
Drug: Placebo
Placebo treatment
|
Outcome Measures
Primary Outcome Measures
- Difference in the composite cardiovascular, respiratory, and renal sequential organ failure assessment (CRR-SOFA) [day 7]
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 [day 28]
Outcome is the number of serious adverse event
- Organ failure free days [day 28]
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 [day 7]
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 [day 7]
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 [day 7]
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 [day 28]
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 [day 28]
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 [day 28]
This outcome is the number of days the patient was admitted to the ICU.
- All-cause mortality [Day 28]
This outcome is the proportion of patients suffering all-cause mortality prior to day 28.
- Peripheral CD3+ senescent (SnCs) immune cells [day 7]
Outcome is the relative expression of p16Ink4a in CD3+ cells.
- Outcome is the relative expression of p16Ink4a in CD3+ cells. [day 28]
Outcome is the relative expression of p16Ink4a in CD3+ cells.
- TNF-alpha [day 7]
Outcome is the concentration of TNF-alpha by Luminex human discovery assay
Eligibility Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- University of Minnesota
Investigators
- Principal Investigator: Michael Puskarich, MD, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HRP-XXX