Fisetin for Sepsis

Recruiting at 9 trial locations

Overseen By Michael Puskarich, MD

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Minnesota

Must not be taking: Vasopressors, Antivirals, Antifungals, others

Disqualifiers: ICU admission, Cancer, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

220 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those on active treatment with potential drug-drug interactions. It's best to discuss your current medications with the trial team.

How is the drug Fisetin unique in treating sepsis?

Fisetin is unique in treating sepsis because it is not a standard antibiotic but a flavonoid, which may offer a novel approach by potentially reducing inflammation and oxidative stress, unlike traditional antibiotics that target bacteria directly. ^{1 2 3 4 5}

Research Team

Michael Puskarich, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

The STOP-Sepsis trial is for people aged 65 or older who are hospitalized with a primary diagnosis of acute infection and expected to stay at least 48 hours. They must have a certain level of organ dysfunction but not severe kidney failure, very low blood counts, invasive fungal infections, or be in intensive care.

Inclusion Criteria

Expected length of stay >=48 hours (per investigator judgment)

I have been admitted to the hospital.

SOFA >1

Exclusion Criteria

Hemoglobin <7 g/dL

Total bilirubin >3X or AST/ALT >4x upper limit of normal

I have been diagnosed with HIV, Hepatitis B, or Hepatitis C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either fisetin or placebo to assess the efficacy in reducing sepsis progression

1 week

Daily visits (in-person) for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of organ failure and mortality

4 weeks

Weekly visits (in-person) for monitoring

Long-term follow-up

Participants are assessed for long-term outcomes such as organ failure free days and overall survival

28 days

Treatment Details

Interventions

• Fisetin-dose 1
• Fisetin-dose 2
• Placebo

Trial Overview This study tests different doses of Fisetin against a placebo to see if they can reduce the severity of sepsis in older patients by targeting aging cells. It's set up so that more successful treatments get tested on more patients as the trial goes on.

Participant Groups

Group I: Fisetin- dose 2 Experimental Treatment 1 Intervention

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.

Group II: Fisetin- dose 1 Experimental Treatment 1 Intervention

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.

Group III: Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

In a study of 197 patients treated for severe sepsis and septic shock, 19.3% experienced significant delays in receiving their second dose of antibiotics, which is critical for effective treatment.

The incidence of delays was notably higher in patients initially treated in inpatient locations (30.3%) compared to those treated in the emergency department (17.1%), highlighting potential areas for improvement in antibiotic administration protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delays in Administration of the Second Antibiotic Dose in Patients With Severe Sepsis and Septic Shock. Randolph, JL., Chan, K., Albright, A., et al.[2022]

In patients with sepsis, traditional dosing strategies for antimicrobials are often ineffective due to significant changes in how the body processes these drugs, necessitating individualized dosing adjustments.

Administering higher initial doses of hydrophilic antimicrobials and using improved methods like continuous infusion can enhance treatment effectiveness and help achieve the desired drug levels in the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic considerations in antimicrobial therapy for sepsis. Fujii, M., Karumai, T., Yamamoto, R., et al.[2021]

In a study of 1075 adults with severe sepsis or septic shock, 31.2% experienced delays in receiving their second dose of antibiotics, particularly influenced by factors like ED boarding and renal failure.

Despite these delays, the study found no significant association between delayed second-dose antibiotics and increased mortality or adverse clinical outcomes, suggesting that timely administration may not be as critical as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock. Lykins V, JD., Kuttab, HI., Rourke, EM., et al.[2022]

A new 'antibiotic champion' process was implemented in a pediatric intensive care unit, resulting in an increase from 29% to 75% of severe sepsis patients receiving their first dose of antibiotics within the recommended 60 minutes after provider order entry.

The median time from provider order entry to antibiotic administration decreased significantly by 36.5 minutes, demonstrating improved efficiency in treating severe sepsis in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Quality Improvement Project Focused on Improving First Dose Antibiotic Timeliness for Pediatric Intensive Care Unit Patients with Severe Sepsis. Keul, R., Rodriguez, J., Coleman, A., et al.[2022]

A new continuous infusion (CI) dosing regimen of vancomycin for septic patients was validated, allowing for rapid attainment of target serum concentrations in most patients, with adequate levels achieved in 73% of patients by 24 hours.

The study involved 107 septic patients in an ICU, and the regimen included a loading dose followed by a daily dose adjusted for kidney function, demonstrating that only 16% of patients had insufficient drug levels at 12 hours, indicating effective dosing strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients. Cristallini, S., Hites, M., Kabtouri, H., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Delays in Administration of the Second Antibiotic Dose in Patients With Severe Sepsis and Septic Shock. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic considerations in antimicrobial therapy for sepsis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A Quality Improvement Project Focused on Improving First Dose Antibiotic Timeliness for Pediatric Intensive Care Unit Patients with Severe Sepsis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients. [2018]