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

University of Minnesota (UMN)

Status and phase: Enrolling; Phase 2

Conditions: Acute Infection; Organ Failure; Sepsis

Treatments: Drug: Fisetin-dose 1; Drug: Placebo; Drug: Fisetin-dose 2

Study type: Interventional

Funder types: Other

Identifiers

NCT05758246

HRP-XXX

Details and patient eligibility

About

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.

Enrollment: 220 estimated patients

Sex: All

Ages: 65+ years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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220 participants in 3 patient groups, including a placebo group

Fisetin- dose 1

Experimental group

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.

Treatment:

Drug: Fisetin-dose 1

Fisetin- dose 2

Experimental group

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.

Treatment:

Drug: Fisetin-dose 2

Placebo

Placebo Comparator group

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.

Treatment:

Drug: Placebo