Epirubicin for the Treatment of Sepsis & Septic Shock

NCT05033808 | Recruiting Phase 2 DMC

• 4 other identifiers: EPOS_ZKSJ01342021-002300-1201EN2001DRKS00025884
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 5

Brief 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. 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.

Conditions

Sepsis

Keywords

epirubicin; disease tolerance; myelotoxicity; pilot study

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 14 days after administration of study drug

Secondary Outcomes (11)

• Survival at day 14, 28 and 90

  14, 28 and 90 days

• SOFA score

  Up to 14 days after administration of study drug

• Cardiotoxicity

  7 days after administration of study drug

• "Success" rate

  3 days after administration of study drug

• Adverse events

  Up to 90 days after administration of study drug

Other Outcomes (6)

• Epirubicin plasma concentrations

  At 15minutes and at 1, 2, 3, 6, 12, and 24 hours after administration of study drug

• DNA damage

  Up to 7 days after administration of study drug

• Cytokines

  Up to 14 days after administration of study drug

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Administration of NaCl i.v. as placebo once.

Drug: Placebo

Epirubicin Phase I

EXPERIMENTAL

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

Drug: Epirubicin

Epirubicin Phase II

EXPERIMENTAL

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

Drug: Epirubicin

Epirubicin Phase III

EXPERIMENTAL

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

Drug: Epirubicin

Interventions

Epirubicin DRUG

Epirubicin is given once over 15 Minutes via a central line

Epirubicin Phase I; Epirubicin Phase II; Epirubicin Phase III

Placebo DRUG

NaCl is given once over 15 Minutes via a central line

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jena University Hospital: lead
• Ruhr University of Bochum: collaborator
• University Medicine Greifswald: collaborator

Study Sites (5)

Jena University Hospital

Jena, Thuringia, 07747, Germany

RECRUITING

University Hospital Knappschafstkrankenhaus Bochum

Bochum, 44892, Germany

NOT YET RECRUITING

University Medicine Greifswald

Greifswald, 17489, Germany

NOT YET RECRUITING

Universitätsklinikum Hamburg Eppendorf

Hamburg, 20251, Germany

NOT YET RECRUITING

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

NOT YET RECRUITING

Related Publications (2)

• 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.

  PMID: 24184056 BACKGROUND

• 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.

  PMID: 38653508 DERIVED

MeSH Terms

Conditions

Sepsis

Interventions

Epirubicin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Sebastian Weis, M.D.

  Jena University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sebastian Weis, M.D.

CONTACT

+49 (0) 3641-932; Sebastian.Weis@med.uni-jena.de

Daniel O Thomas-Rüddel, M.D.

CONTACT

+49 (0) 3641-932; Daniel.Thomas@med.uni-jena.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study medication is provided in colored infusion bags with additional covers
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Sequential dose escalation with three dosing groups and placebo.

Study Record Dates

• First Submitted: August 4, 2021
• First Posted: September 5, 2021
• Study Start: October 19, 2022
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 12, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (5)