Aminoglycosides in Early Sepsis

NCT06712641 | Recruiting Phase 4 DMC

• 1 other identifier: 2024-519797-39-00
• Study Type: interventional
• Target: 1,900
• Locations: 1 country
• Sites: 5

Brief Summary

Norwegian guidelines for empirical antibiotic therapy in suspected community acquired sepsis recommend the combination of narrow spectrum betalactam and aminoglycoside as the first choice, but broad spectrum betalactams are considered equally appropriate, effective, and safe. However, fear of renal complications due to gentamicin and concern for lacking evidence for efficiency commonly leads to the use of broad spectrum betalactam therapy, a larger driver of antibiotic resistance. In patients with suspected community acquired sepsis, the investigators hypothesize that empirical combination therapy with narrow spectrum betalactams and aminoglycosides is safe and non-inferior to empirical therapy with broad spectrum betalactams. More specifically, the investigators hypothesize that the proportion of patients with acute kidney injury or death will be similar between these two treatment groups. Furthermore, the investigators hypothesize that the aminoglycoside-based regimen has lesser impact on the gut microbiome. Antimicrobial resistance is one of the most urgent health threats of our time, and Norwegian hospitals were required but failed to reduce the use of broad-spectrum antibiotics with 30% by the end of 2020. In this context, novel initiatives aiming at reducing use of antibiotics are direly needed.

Conditions

Sepsis

Keywords

sepsis; antibiotics; aminoglycosides; cephalosporins

Outcome Measures

Primary Outcomes (2)

• 30-day mortality

  All-cause mortality up to 30 days after randomization

  Up to 30 days after randomization

• 30-day acute kidney injury

  Any acute kidney injury up to 30 days after randomization

  Up to 30 days after randomization

Secondary Outcomes (8)

• In-hospital mortality

  During index hospitalization (commonly up to 30 days)

• Duration of hospital stay

  During index hospitalization (commonly up to 30 days)

• Duration of intensive care stay

  During index hospitalization (commonly up to 30 days)

• Duration of ventilator therapy

  During index hospitalization (commonly up to 30 days)

• Duration of vasopressor therapy

  During index hospitalization (commonly up to 30 days)

Study Arms (2)

Gentamicin + narrow spectrum betalactam

ACTIVE COMPARATOR

Empirical therapy for suspected community-acquired sepsis with gentamicin + narrow spectrum betalactam (either one of penicillin, ampicillin, or cloxacillin)

Drug: Gentamicin + narrow spectrum betalactam

Cefotaxime or piperacillin-tazobactam

ACTIVE COMPARATOR

Empirical therapy for suspected community-acquired sepsis with broad spectrum betalactam (either one of cefotaxime or piperacillin-tazobactam)

Drug: Cefotaxime; Drug: Piperacillin-tazobactam

Interventions

Gentamicin + narrow spectrum betalactam DRUG

Empirical therapy for suspected community-acquired sepsis with gentamicin + narrow spectrum betalactam (either one of penicillin, ampicillin, or cloxacillin)

Gentamicin + narrow spectrum betalactam

Cefotaxime DRUG

Empirical therapy for suspected community-acquired sepsis with cefotaxime

Cefotaxime or piperacillin-tazobactam

Piperacillin-tazobactam DRUG

Empirical therapy for suspected community-acquired sepsis with piperacillin-tazobactam

Cefotaxime or piperacillin-tazobactam

Eligibility Criteria

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

You may qualify if:

• Hospitalized
• Adults 18 year or older
• Clinical suspicion of community acquired sepsis with indication for empirical antibiotic therapy
• National Early Warning Score 2 (NEWS2) ≥ 5
• Signed informed consent must be obtained and documented according to ICH GCP, and national/local regulations

You may not qualify if:

• Established chronic kidney failure (eGFR \< 30 ml/min/1.73m2)
• Presentation with septic shock with multiorgan failure
• Suspicion of condition necessitating specific antimicrobial therapy (e.g. atypical pneumonia, fungal infection, parasitic infection, mycobacterial infection)
• Current or recent use of nephrotoxic drugs (e.g cisplatin within previous 2 months)
• Suspected or confirmed carrier of extended spectrum betalactamase (ESBL) producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), or other drug-resistant microbes necessitating specific antimicrobial therapy
• Multiple myeloma
• Renal transplantation
• Renal replacement therapy
• Myasthenia gravis
• Known hypersensitivity to any of the study drugs
• Pregnancy

Sponsors & Collaborators

• University Hospital, Akershus: lead
• Ullevaal University Hospital: collaborator

Study Sites (5)

Haukeland University Hospital

Bergen, Bergen, Norway

NOT YET RECRUITING

Lovisenberg Diakonal Hospital

Oslo, Oslo, Norway

NOT YET RECRUITING

St. Olav's Hospital

Trondheim, Trondheim, Norway

NOT YET RECRUITING

Akershus University Hospital

Lørenskog, 1478, Norway

RECRUITING

Oslo University Hospital Ullevål

Oslo, 0450, Norway

RECRUITING

MeSH Terms

Conditions

Sepsis

Interventions

Gentamicins; Cefotaxime; Piperacillin, Tazobactam Drug Combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoglycosides; Glycosides; Carbohydrates; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Tazobactam; Penicillanic Acid; Penicillins; Piperacillin; Ampicillin; Penicillin G; Sulfones; Drug Combinations; Pharmaceutical Preparations

Central Study Contacts

Magnus N Lyngbakken, MD PhD

CONTACT

+4793408837; magnus.lyngbakken@medisin.uio.no

Kristian Tonby, MD PhD

CONTACT

+4741550565; kristian.tonby@medisin.uio.no

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 27, 2024
• First Posted: December 2, 2024
• Study Start: April 23, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): May 1, 2033
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

NO (5)