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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called fisetin, a plant-based compound, to determine if it can reduce the severity of sepsis, a serious infection that can lead to organ failure. Researchers are evaluating two different doses of fisetin to identify the most effective one and assess its ability to prevent further complications. The trial targets individuals aged 65 or older who have been hospitalized with an infection and exhibit symptoms of sepsis. Participants should not be in the ICU or receiving intensive treatments like ventilators or dialysis. The study aims to improve care for older patients facing severe infections. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that fisetin, a potential treatment for sepsis, produced promising results in earlier studies. Specifically, fisetin reduced inflammation and improved organ function in animal tests. For instance, studies found that fisetin lowered inflammation and enhanced lung function in animals with sepsis. Another study demonstrated that fisetin reduced the effects of septic shock in zebrafish, resulting in fewer deaths.

In humans, fisetin is currently undergoing testing to assess its tolerability. This Phase 2 study indicates that the treatment has already passed initial safety tests. Although detailed information on humans is not yet available, reaching this phase suggests that early tests did not reveal major safety issues. However, further research is necessary to fully understand its safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about fisetin for sepsis because it offers a fresh approach to treating this life-threatening condition. Unlike standard treatments like antibiotics and supportive care, fisetin is a plant-derived flavonoid that may reduce inflammation and oxidative stress, which are key players in sepsis. This unique mechanism of action has the potential to improve outcomes by addressing the underlying causes of organ failure in sepsis, rather than just managing symptoms. Fisetin is being tested in two different doses, providing an opportunity to explore the most effective way to harness its benefits.

What evidence suggests that this trial's treatments could be effective for sepsis?

This trial will compare two different doses of fisetin with a placebo to evaluate its effectiveness in treating sepsis. Research has shown that fisetin, a natural substance found in plants, might help treat sepsis by reducing inflammation and preventing organ damage. Studies have found that fisetin can lower levels of certain chemicals in the body that worsen sepsis. Fisetin also helps remove old and damaged cells that can be harmful. By targeting these cells, fisetin may lessen the impact of sepsis, especially in older people. Early research suggests this could be a promising way to treat sepsis and improve organ function. ^{1 2 3 5 6}

Who Is on the Research Team?

Michael Puskarich, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11492760/

Senolytics To slOw Progression of Sepsis (STOP-Sepsis) in ... The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0047637424000952

Fisetin as a senotherapeutic agent: Evidence and ... Our review of available data suggests that targeting senescent cells with fisetin offers a promising strategy for managing multiple chronic diseases.

3. withpower.com withpower.com/trial/phase-2-sepsis-3-2023-6e5aa

Fisetin for Sepsis · Recruiting Participants for Phase ... The long-term goal is to test the clinical efficacy of senolytic therapies to reduce progression to and severity of sepsis in older patients.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7608145/

Fisetin alleviates sepsis-induced multiple organ ... Fisetin significantly reduced the expression of inflammatory cytokines and ameliorated sepsis-induced multiple organ failure by attenuating lung ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39434114/

Senolytics To slOw Progression of Sepsis (STOP ... - PubMed The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection.

6. nature.com nature.com/articles/s41598-021-87257-0

Fisetin inhibits lipopolysaccharide-induced inflammatory ... Altogether, these data indicate that fisetin attenuates LPS-induced septic shock in zebrafish larvae accompanied by decreased mortality ...