A Phase 2 interventional study of Epirubicin and Placebo in Sepsis, sponsored by Jena University Hospital. Recruiting at 5 sites in Germany. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-12.
Sponsored by Jena University Hospital · Phase 2, Interventional, and Treatment
The study will assess the safety of low doses of epirubicin in sepsis patients. Therefore the study will look for side effects in patients treated with low dose epirubicin compared to control patients.
In animals, low dose epirubicin has been shown to induce tolerance to infection and increase survival in septic mice.
The study will also look for positive effects on organ function in humans. The investigators hypothesize that low-dose epirubicin can be used therapeutically to improve the disease course and lessen mortality of patients with sepsis. In a first step, the investigators aim at proving that low-dose epirubicin can safely be administered to sepsis patients and will perform a dose-escalation multi-center trial.
There are two ways for organism to deal with infection. Resistance, which means elimination of infectious microorganisms by the immune system, is widely recognized. It can be supported by antibiotic medication and surgical or interventional drainage of an infectious focus. The other response is tolerance, which means limiting organ damage without fighting the infection itself. Its importance has become more clearly recently, but so far there are no therapeutic interventions to support this mechanism.
Epirubicin is a chemotherapeutic substance used to treat cancer. In animal experiments, it has been shown that doses much lower than the ones used in oncology, can induce tolerance in infected animals. Animals treated with epirubicin survive an infectious dose that kills animals not treated with epirubicin. Before this approach can be studied in a large group of sepsis patients, it is necessary that epirubicin in low doses can be safely used in this population.
Therefore in this study, septic patients will be treated with low doses of epirubicin and systematically assessed for serious side effects. Some patients will be treated with placebo for comparison. The trial will be conducted as a dose escalation study with three groups. This means that the first group of patients will receive only a quarter of the dose shown to be effective in animal experiments. Only if no serious side effects are observed will the dose be increased in the second group and again in the third group.
In addition, the study will look for signs of beneficial effects on organ function in human patients with sepsis, pharmacokinetics of epirubicin in sepsis patients and changes in the inflammatory response.
The investigators hypothesize that low-dose epirubicin can be used therapeutically to improve the disease course and lessen mortality of patients with sepsis. In a first step, the investigators aim at proving that low-dose epirubicin can safely be administered to sepsis patients and will perform a phase IIa dose-escalation multi-center trial.
1,894 studies on the registry are indexed under Sepsis; 458 are open to participants now.
This study's planned enrollment of 45 is below the median of 105 across 893 interventional studies indexed under Sepsis.
Browse Sepsis studies →Jena University Hospital is the lead sponsor of 62 studies on the registry; 19 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Administration of NaCl i.v. as placebo once.
Drug: Placebo
Administration of epirubicin i.v. 3.75 mg/m2 once.
Drug: Epirubicin
Administration of epirubicin i.v. 7.5 mg/m2 once.
Drug: Epirubicin
Administration of epirubicin i.v. 15 mg/m2 once.
Drug: Epirubicin
Epirubicin is given once over 15 Minutes via a central line
NaCl is given once over 15 Minutes via a central line
Number of participants with myelotoxicity
Neutropenia or thrombocytopenia of grade 3 or 4 (neutrophiles \<1,000μL or platelets \<50,000/μL) at two consecutive study visits up to day 14 accompanied by neutropenia or thrombocytopenia of grade 2, 3 or 4 (neutrophiles \<1,500μL or platelets \<75,000/μL) at both study visits and accompanied by an IPF (immature platelet fraction) below 2.5% at one or two of the consecutive study visits.
Time frame: Up to 14 days after administration of study drug
Survival at day 14, 28 and 90
Survival
Time frame: 14, 28 and 90 days
SOFA score
SOFA (sequential organ failure assessment) on days of assessment, mean total SOFA and SOFA changes over time
Time frame: Up to 14 days after administration of study drug
Cardiotoxicity
Ejection fraction measured via TTE (trans-thoracic echocardiography)
Time frame: 7 days after administration of study drug
"Success" rate
Decrease of procalcitonin (PCT) serum concentration by 80% or more of its intra-individual peak value or to 0.5 μg/L or lower within 72 hours after randomization
Time frame: 3 days after administration of study drug
Adverse events
Overall rate of adverse and severe adverse events. The the frequency of other typical side effects (diarrhea, mucositis, alopecia, nausea and vomiting).
Time frame: Up to 90 days after administration of study drug
Quality of life assesed by the SF-36 questionaire
The short Form 36 Health Questionnaire (SF-36) contains 36 questions on quality of life. From the answers a Physical Component Summary (PCS) and a Mental Component Summary (MCS) are calculated, both ranging approximately from 0 (severe disability) up to 80 (absence of disability).
Time frame: At follow up 90 days after administration of study drug
Fluid balance and urine output
Assessment of fluid balance and urine output
Time frame: Up to 14 days after administration of study drug
Need for renal replacement therapy
Use of renal replacement therapy for chronic or acute kidney failure
Time frame: Up to 14 days after administration of study drug
Oxygenation index (paO2/FiO2)
The ratio of arterial oxygen partial pressure and the fraction of inhaled oxygen will be calculated. For patients receiving conventional low flow oxygen FiO2 will be estimated based on a predefined table.
Time frame: Up to 14 days after administration of study drug
Need for respiratory support
The highest level of respiratory support will be documented.
Time frame: Up to 14 days after administration of study drug
Need for catecholamines and inotropes
For all catecholamines and inotropes the highest daily rate administerd for at least one hour will be documented.
Time frame: Up to 14 days after administration of study drug
Epirubicin plasma concentrations
Epirubicin concentrations in the plasma will be measured using mass-spectrometry
Time frame: At 15minutes and at 1, 2, 3, 6, 12, and 24 hours after administration of study drug
DNA damage
DNA damage in peripheral mononuclear blood cells (PBMC) will be assessed. Further assessment of molecular parameters from the PBMCs reflecting epirubicin effects on the DNA or damage control pathways will be performed subsequently
Time frame: Up to 7 days after administration of study drug
Cytokines
Plasma cytokines will be determined in all patients using Luminex xMAP or alike multiplex technology
Time frame: Up to 14 days after administration of study drug
Organ damage markers
Non-conventional sensitive organ damage markers (e.g. NGAL) will be measured
Time frame: Up to 14 days after administration of study drug
Anti-PF4 anti-bodies
Determination of anti-PF4 (platelet factor 4) anti-bodies
Time frame: Up to 14 days after administration of study drug
Mitochondrial function
Molecular parameters for mitochondrial function will be assessed from isolated PBMCs
Time frame: Up to 7 days after administration of study drug
Plan to share: No
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Jena University Hospital