Fisetin for Sepsis
Recruiting in Palo Alto (17 mi)
+9 other locations
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Minnesota
Must not be taking: Vasopressors, Antivirals, Antifungals, others
Disqualifiers: ICU admission, Cancer, HIV, others
Prior Safety Data
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.
12345Eligibility 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
+2 more
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.
+13 more
Trial 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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Placebo Group
Group I: Fisetin- dose 2Experimental Treatment1 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 1Experimental Treatment1 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: PlaceboPlacebo Group1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
HCMCMinneapolis, MN
UMMCMinneapolis, MN
RidgesBurnsville, MN
SouthdaleEdina, MN
More Trial Locations
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Who Is Running the Clinical Trial?
University of MinnesotaLead Sponsor
References
Delays in Administration of the Second Antibiotic Dose in Patients With Severe Sepsis and Septic Shock. [2022]Purpose: The aim of this study was to determine the incidence of significant delays in administration of the second antibiotic dose in patients treated for severe sepsis and septic shock at a single community teaching hospital as well as to assess patient outcomes associated with second dose delays. Methods: This single-center, retrospective chart review evaluated patients who received at least 2 antibiotic doses for severe sepsis or septic shock. Patients were classified as having experienced a significant second dose delay if the actual interval between the first and the second antibiotic doses was greater than or equal to 125% of the recommended dosing interval. Results: Of 197 patients, 38 (19.3%) experienced a significant second antibiotic dose delay. The rate of significant delays was 17.1% in patients treated initially in the emergency department and 30.3% in patients treated initially in another inpatient location. Conclusions: This single-center study found a 19.3% rate of significant delays in antibiotic second dose administration in patients with severe sepsis and septic shock. This study was not powered to identify differences in outcomes in patients with and without significant second dose delays. Additional large-scale studies are needed to investigate the impact of antibiotic second dose delays on outcomes in patients with sepsis.
Pharmacokinetic and pharmacodynamic considerations in antimicrobial therapy for sepsis. [2021]Introduction: Antimicrobial dose optimization for the treatment of sepsis remains challenging because of dynamic pharmacokinetic alterations and physiological/pathological responses of the host. Subtherapeutic plasma levels of antimicrobials are commonly observed in patients with sepsis, which potentially leads to both treatment failure and emergence of antimicrobial resistance. The knowledge of antimicrobial pharmacokinetics and pharmacodynamics is helpful in order to tailor antimicrobial dosing strategies.Areas covered: This narrative review summarizes pharmacokinetic alterations of antimicrobial agents and provides useful information on antimicrobial dose optimization. Literature was searched using PubMed database, focusing on pharmacokinetics and pharmacodynamics of antibacterial and antifungal agents in sepsis.Expert opinion: In patients with sepsis, increased volume of distribution and variable changes in renal clearance are the two major factors for antimicrobial pharmacokinetic alterations. Traditional 'one-dose-fits-all' dosing strategy is not suitable for patients with sepsis and hence individualized antimicrobial dosing adjustment is preferable. In general, the initial dose of hydrophilic antimicrobials such as ß-lactams, aminoglycosides, and vancomycin should be given at a high dose regardless of renal function. Improved methods of drug administration (e.g. extended/continuous infusion of β-lactams) help to increase the chance of pharmacodynamic target attainment. The use of therapeutic drug monitoring should be considered where available.
The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock. [2022]Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes.
A Quality Improvement Project Focused on Improving First Dose Antibiotic Timeliness for Pediatric Intensive Care Unit Patients with Severe Sepsis. [2022]Recommended time to start administration of first dose antibiotics for sepsis patients is 60 minutes from time 0. Institution-specific data revealed that only one-quarter of severe sepsis patients were meeting this goal when measured from the time of provider order entry. Reliance on a pneumatic tube system for first-dose antibiotic delivery was deemed largely responsible for this finding. This project aimed to increase the percentage of pediatric intensive care unit patients with severe sepsis receiving first dose antibiotics within 60 minutes of provider order entry to ≥50%.
New Regimen for Continuous Infusion of Vancomycin in Critically Ill Patients. [2018]Despite the development of new agents with activity against Gram-positive bacteria, vancomycin remains one of the primary antibiotics for critically ill septic patients. Because sepsis can alter antimicrobial pharmacokinetics, the development of an appropriate dosing strategy to provide adequate concentrations is crucial. The aim of this study was to prospectively validate a new dosing regimen of vancomycin given by continuous infusion (CI) to septic patients. We included all adult septic patients admitted to a mixed intensive care unit (ICU) between January 2012 and May 2013, who were treated with a new vancomycin CI regimen consisting of a loading dose of 35 mg/kg of body weight given as a 4-h infusion, followed by a daily CI dose adapted to creatinine clearance (CrCL), as estimated by the Cockcroft-Gault formula (median dose, 2,112 [1,500 to 2,838] mg). Vancomycin concentrations were measured at the end of the loading dose (T1), at 12 h (T2), at 24 h (T3), and the day after the start of therapy (T4). Vancomycin concentrations of 20 to 30 mg/liter at T2, T3, and T4 were considered adequate. A total of 107 patients (72% male) were included. Median age, weight, and CrCL were 59 (interquartile range [IQR], 48 to 71) years, 75 (IQR, 65 to 85) kg, and 94 (IQR, 56 to 140) ml/min, respectively. Vancomycin concentrations were 44 (IQR, 37 to 49), 25 (IQR, 21 to 32), 22 (IQR, 19 to 28), and 26 (IQR, 22 to 29) mg/liter at T1, T2, T3, and T4, respectively. Concentrations were adequate in 56% (60/107) of patients at T2, in 54% (57/105) at T3, and in 73% (41/56) at T4. This vancomycin regimen permitted rapid attainment of target concentrations in serum for most patients. Concentrations were insufficient in only 16% of patients at 12 h of treatment.