SepsisPhase 2EPOS-1NCT05033808
Epirubicin for the Treatment of Sepsis & Septic Shock
A Phase 2 study testing Epirubicin in people with Sepsis, run by Jena University Hospital at 5 sites in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Epirubicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 5 sitesGermany
- Study dates
- 19 Oct 2022to Dec 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- admitted to the ICU with sepsis or septic shock, diagnosed within the previous 24 hours
Who cannot join
- Leukopenia/Neutropenia/Thrombocytopenia-prior or upon inclusion (Leucocyte Count <4000/μL; Neutrophile/ platelets Count below Lower Limit of Normal).
- Weight >135 kg/BMI >45.
- Active neoplasia.
- History of chemotherapy.
- Hypersensitivity to epirubicin
- History of bone marrow or solid organ transplantation.
Show all 17Show fewer
- Immunosuppressive therapy.
- Acute severe infection within 4 weeks prior to admission (Hospitalization or admission to higher level clinical care facility for infection).
- Chronic infection.
- Cardiomyopathy with a documented ejection fraction <30% or AICD (automatic internal cardioverter defibrillator) implantation.
- Acute liver failure following the European Association for the Study of the Liver definition as International Normalized Ratio (INR) >1.5 and elevation of transaminases > 3 times of the upper normal limit (2).
- Pregnancy during all trimesters/breast-feeding.
- Chronic mechanical ventilation dependency.
- Cystic fibrosis.
- Concomitant medication with Verapamil or Cimetidine.
- Prior enrollment in this study.
- Participation in another clinical intervention trial.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Germany5 sites, 5 recruiting
- Not yet recruiting
University Hospital Knappschafstkrankenhaus Bochum
Bochum, 44892
Tim Rahmel, M.D., +49 234 299 ext. 80025, Tim.Rahmel@kk-bochum.de
Hartmuth Nowak, M.D., +49 (234) 299 ext. 80039, hartmuth.nowak@kk-bochum.de
- Not yet recruiting
University Medicine Greifswald
Greifswald, 17489
Matthias Gründling, M.D., +49 (0) 3834 86 ext. 5810, matthias.gruendling@med.uni-greifswald.de
Sven-Olaf Kuhn, M.D., +49 (0) 3834 86 ext. 5801, sven-olaf.kuhn@med.uni-greifswald.de
- Not yet recruiting
Universitätsklinikum Hamburg Eppendorf
Hamburg, 20251
Axel Nierhaus, M.D., +49 (0) 40 7410 ext. 55325, nierhaus@uke.de
Grit Ringeis, +49 (0) 40 7410 ext. 35315, g.ringeis@uke.de
- Recruiting
Jena University Hospital
Jena, Thuringia, 07747
Sebastian Weis, M.D., +49 (0) 3641-932 ext. 3100, Sebastian.Weis@med.uni-jena.de
Daniel O Thomas-Rüddel, M.D., +49 (0) 3641-932 ext. 3267, Daniel.Thomas@med.uni-jena.de
- Not yet recruiting
Universitätsklinikum Würzburg
Würzburg, 97080
Patrick Meybohm, Prof., +(49)931-201 ext. 30000, meybohm_p@ukw.de
Eva Kranke, +(49)931-201 ext. 30024, kranke_e@ukw.de
About this study
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.
Read the detailed description
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.
- Conditions
- Sepsis
- Being tested
- Epirubicin, Placebo
- Keywords
- epirubicin, disease tolerance, myelotoxicity, pilot study
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EpirubicinDrug
Epirubicin is given once over 15 Minutes via a central line
PlaceboDrug
NaCl is given once over 15 Minutes via a central line
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Administration of NaCl i.v. as placebo once. Receives: Drug: Placebo |
| Epirubicin Phase I | Experimental | Administration of epirubicin i.v. 3.75 mg/m2 once. Receives: Drug: Epirubicin |
| Epirubicin Phase II | Experimental | Administration of epirubicin i.v. 7.5 mg/m2 once. Receives: Drug: Epirubicin |
| Epirubicin Phase III | Experimental | Administration of epirubicin i.v. 15 mg/m2 once. Receives: Drug: Epirubicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 14 days after administration of study drug
Secondary outcomes (11)
Survival at day 14, 28 and 90
Survival
Measured: 14, 28 and 90 days
SOFA score
SOFA (sequential organ failure assessment) on days of assessment, mean total SOFA and SOFA changes over time
Measured: Up to 14 days after administration of study drug
Cardiotoxicity
Ejection fraction measured via TTE (trans-thoracic echocardiography)
Measured: 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
Measured: 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).
Measured: 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).
Measured: At follow up 90 days after administration of study drug
Fluid balance and urine output
Assessment of fluid balance and urine output
Measured: 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
Measured: 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.
Measured: Up to 14 days after administration of study drug
Need for respiratory support
The highest level of respiratory support will be documented.
Measured: 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.
Measured: Up to 14 days after administration of study drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2021
- Study start19 Oct 2022
- Primary completionOct 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Sequential dose escalation with three dosing groups and placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jena University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Ruhr University of Bochum, University Medicine Greifswald
- Responsible party
- Sponsor
- Investigators
- Sebastian Weis, M.D., Principal investigator, Jena University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05033808
- Sponsor's protocol ID
- EPOS_ZKSJ0134
- Other IDs
- 2021-002300-12, 01EN2001, DRKS00025884
- Acronym
- EPOS-1
- Status last verified
- Feb 2024
- First submitted
- 4 Aug 2021
- Last updated
- 12 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, Neves-Costa A, Moita C, Pedroso D, Pinto A, Marques S, Faridi H, Costa P, Gozzelino R, Zhao JL, Soares MP, Gama-Carvalho M, Martinez J, Zhang Q, Doring G, Grompe M, Simas JP, Huber TB, Baltimore D, Gupta V, Green DR, Ferreira JA, Moita LF. Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity. 2013 Nov 14;39(5):874-84. doi: 10.1016/j.immuni.2013.08.039. Epub 2013 Oct 31.
PubMed 24184056Thomas-Ruddel D, Bauer M, Moita LF, Helbig C, Schlattmann P, Ehler J, Rahmel T, Meybohm P, Grundling M, Schenk H, Kocher T, Brunkhorst FM, Graler M, Heger AJ, Weis S; EPOS-1 study group; SepNetCriticalCare TrialsGroup. Epirubicin for the Treatment of Sepsis and Septic Shock (EPOS-1): study protocol for a randomised, placebo-controlled phase IIa dose-escalation trial. BMJ Open. 2024 Apr 22;14(4):e075158. doi: 10.1136/bmjopen-2023-075158.
PubMed 38653508
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epirubicin for the Treatment of Sepsis & Septic Shock
- ClinicalTrials.gov ID
- NCT05033808
- Acronym / sponsor ID
- EPOS-1 / EPOS_ZKSJ0134
- Conditions
- Sepsis
- Keywords
- epirubicin, disease tolerance, myelotoxicity, pilot study
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Jena University HospitalUniversity, hospital or other
- Collaborators
- Ruhr University of Bochum, University Medicine Greifswald
- Study start
- 19 Oct 2022 (actual)
- Primary completion
- Oct 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 5 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Sequential dose escalation with three dosing groups and placebo.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboAdministration of NaCl i.v. as placebo once. |
| Epirubicin Phase I | Experimental | Drug: EpirubicinAdministration of epirubicin i.v. 3.75 mg/m2 once. |
| Epirubicin Phase II | Experimental | Drug: EpirubicinAdministration of epirubicin i.v. 7.5 mg/m2 once. |
| Epirubicin Phase III | Experimental | Drug: EpirubicinAdministration of epirubicin i.v. 15 mg/m2 once. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- admitted to the ICU with sepsis or septic shock, diagnosed within the previous 24 hours
Key exclusion criteria (17 listed)
- Leukopenia/Neutropenia/Thrombocytopenia-prior or upon inclusion (Leucocyte Count <4000/μL; Neutrophile/ platelets Count below Lower Limit of Normal).
- Weight >135 kg/BMI >45.
- Active neoplasia.
- History of chemotherapy.
- Hypersensitivity to epirubicin
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EpirubicinEpirubicin is given once over 15 Minutes via a central line | Drug | Epirubicin Phase I, Epirubicin Phase II, Epirubicin Phase III |
| PlaceboNaCl is given once over 15 Minutes via a central line | Drug | Placebo |
Primary outcome
Number of participants with myelotoxicity
Time frame: Up to 14 days after administration of study drug
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.
11 secondary outcomes
Survival at day 14, 28 and 90
Time frame: 14, 28 and 90 days
SOFA score
Time frame: Up to 14 days after administration of study drug
Cardiotoxicity
Time frame: 7 days after administration of study drug
"Success" rate
Time frame: 3 days after administration of study drug
Adverse events
Time frame: Up to 90 days after administration of study drug
Quality of life assesed by the SF-36 questionaire
Time frame: At follow up 90 days after administration of study drug
Fluid balance and urine output
Time frame: Up to 14 days after administration of study drug
Need for renal replacement therapy
Time frame: Up to 14 days after administration of study drug
Oxygenation index (paO2/FiO2)
Time frame: Up to 14 days after administration of study drug
Need for respiratory support
Time frame: Up to 14 days after administration of study drug
Need for catecholamines and inotropes
Time frame: Up to 14 days after administration of study drug
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2024.
- Background: PubMed 24184056Figueiredo N, Chora A, Raquel H, Pejanovic N, Pereira P, Hartleben B, Neves-Costa A, Moita C, Pedroso D, Pinto A, Marques S, Faridi H, Costa P, Gozzelino R, Zhao JL, Soares MP, Gama-Carvalho M, Martinez J, Zhang Q, Doring G, Grompe M, Simas JP, Huber TB, Baltimore D, Gupta V, Green DR, Ferreira JA, Moita LF. Anthracyclines induce DNA damage response-mediated protection against severe sepsis. Immunity. 2013 Nov 14;39(5):874-84. doi: 10.1016/j.immuni.2013.08.039. Epub 2013 Oct 31.
- Derived from this study: PubMed 38653508Thomas-Ruddel D, Bauer M, Moita LF, Helbig C, Schlattmann P, Ehler J, Rahmel T, Meybohm P, Grundling M, Schenk H, Kocher T, Brunkhorst FM, Graler M, Heger AJ, Weis S; EPOS-1 study group; SepNetCriticalCare TrialsGroup. Epirubicin for the Treatment of Sepsis and Septic Shock (EPOS-1): study protocol for a randomised, placebo-controlled phase IIa dose-escalation trial. BMJ Open. 2024 Apr 22;14(4):e075158. doi: 10.1136/bmjopen-2023-075158.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sebastian Weis, M.D. principal investigator
Jena University Hospital
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Epirubicin in people with Sepsis, run by Jena University Hospital at 5 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sebastian Weis, M.D. (+49 (0) 3641-932 ext. 3100, Sebastian.Weis@med.uni-jena.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with myelotoxicity (time frame: Up to 14 days after administration of study drug). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05033808, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2024.