Aminoglycosides in Early Sepsis

NCT ID: NCT06712641

Last Updated: 2025-08-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1900 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-31
• Study Completion Date: 2033-05-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gentamicin + narrow spectrum betalactam

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

Group Type: ACTIVE_COMPARATOR

Gentamicin + narrow spectrum betalactam

Intervention Type: DRUG

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

Cefotaxime or piperacillin-tazobactam

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

Group Type: ACTIVE_COMPARATOR

Cefotaxime

Intervention Type: DRUG

Empirical therapy for suspected community-acquired sepsis with cefotaxime

Piperacillin-tazobactam

Intervention Type: DRUG

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

Interventions

Gentamicin + narrow spectrum betalactam

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

Intervention Type: DRUG

Cefotaxime

Empirical therapy for suspected community-acquired sepsis with cefotaxime

Intervention Type: DRUG

Piperacillin-tazobactam

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ullevaal University Hospital

OTHER

Sponsor Role: collaborator

University Hospital, Akershus

OTHER

Sponsor Role: lead

Responsible Party

Magnus Nakrem Lyngbakken

Postdoctoral fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Akershus University Hospital

Lørenskog, , Norway

Oslo University Hospital Ullevål

Oslo, , Norway

Countries

Norway

Central Contacts

Magnus N Lyngbakken, MD PhD

Role: CONTACT

magnus.lyngbakken@medisin.uio.no

+4793408837

Kristian Tonby, MD PhD

Role: CONTACT

kristian.tonby@medisin.uio.no

+4741550565

Facility Contacts

Magnus N Lyngbakken, MD PhD

Role: primary

magnus.lyngbakken@medisin.uio.no

+4793408837

Jan Erik Berdal, MD PhD

Role: backup

Jan-Erik.Berdal@ahus.no

+4748205817

Kristian Tonby, MD PhD

Role: primary

kristian.tonby@medisin.uio.no

+4741550565

Aleksander R Holten, MD PhD

Role: backup

aleksander.holten@gmail.com

+4799275784

Other Identifiers

2024-519797-39-00

Identifier Type: -

Identifier Source: org_study_id