Epirubicin for the Treatment of Sepsis & Septic Shock

NCT ID: NCT05033808

Last Updated: 2024-03-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-19

Study Completion Date

2024-12-31

Brief Summary

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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

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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

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Sepsis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Sequential dose escalation with three dosing groups and placebo.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Study medication is provided in colored infusion bags with additional covers

Study Groups

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Placebo

Administration of NaCl i.v. as placebo once.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

NaCl is given once over 15 Minutes via a central line

Epirubicin Phase I

Administration of epirubicin i.v. 3.75 mg/m2 once.

Group Type EXPERIMENTAL

Epirubicin

Intervention Type DRUG

Epirubicin is given once over 15 Minutes via a central line

Epirubicin Phase II

Administration of epirubicin i.v. 7.5 mg/m2 once.

Group Type EXPERIMENTAL

Epirubicin

Intervention Type DRUG

Epirubicin is given once over 15 Minutes via a central line

Epirubicin Phase III

Administration of epirubicin i.v. 15 mg/m2 once.

Group Type EXPERIMENTAL

Epirubicin

Intervention Type DRUG

Epirubicin is given once over 15 Minutes via a central line

Interventions

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Epirubicin

Epirubicin is given once over 15 Minutes via a central line

Intervention Type DRUG

Placebo

NaCl is given once over 15 Minutes via a central line

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* admitted to the ICU with sepsis or septic shock, diagnosed within the previous 24 hours

Exclusion Criteria

* 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.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ruhr University of Bochum

OTHER

Sponsor Role collaborator

University Medicine Greifswald

OTHER

Sponsor Role collaborator

Jena University Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sebastian Weis, M.D.

Role: PRINCIPAL_INVESTIGATOR

Jena University Hospital

Locations

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Jena University Hospital

Jena, Thuringia, Germany

Site Status RECRUITING

University Hospital Knappschafstkrankenhaus Bochum

Bochum, , Germany

Site Status NOT_YET_RECRUITING

University Medicine Greifswald

Greifswald, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Hamburg Eppendorf

Hamburg, , Germany

Site Status NOT_YET_RECRUITING

Universitätsklinikum Würzburg

Würzburg, , Germany

Site Status NOT_YET_RECRUITING

Countries

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Germany

Central Contacts

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Sebastian Weis, M.D.

Role: CONTACT

+49 (0) 3641-932 ext. 3100

Daniel O Thomas-Rüddel, M.D.

Role: CONTACT

+49 (0) 3641-932 ext. 3267

Facility Contacts

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Sebastian Weis, M.D.

Role: primary

+49 (0) 3641-932 ext. 3100

Daniel O Thomas-Rüddel, M.D.

Role: backup

+49 (0) 3641-932 ext. 3267

Tim Rahmel, M.D.

Role: primary

+49 234 299 ext. 80025

Hartmuth Nowak, M.D.

Role: backup

+49 (234) 299 ext. 80039

Matthias Gründling, M.D.

Role: primary

+49 (0) 3834 86 ext. 5810

Sven-Olaf Kuhn, M.D.

Role: backup

+49 (0) 3834 86 ext. 5801

Axel Nierhaus, M.D.

Role: primary

+49 (0) 40 7410 ext. 55325

Grit Ringeis

Role: backup

+49 (0) 40 7410 ext. 35315

Patrick Meybohm, Prof.

Role: primary

+(49)931-201 ext. 30000

Eva Kranke

Role: backup

+(49)931-201 ext. 30024

References

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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.

Reference Type BACKGROUND
PMID: 24184056 (View on PubMed)

Thomas-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.

Reference Type DERIVED
PMID: 38653508 (View on PubMed)

Other Identifiers

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2021-002300-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

01EN2001

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DRKS00025884

Identifier Type: REGISTRY

Identifier Source: secondary_id

EPOS_ZKSJ0134

Identifier Type: -

Identifier Source: org_study_id

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