Aminoglycosides in Early Sepsis

Phase 4

Not yet recruiting

• Conditions: Sepsis
• Interventions: Drug: Gentamicin + narrow spectrum betalactam; Drug: Cefotaxime; Drug: Piperacillin-tazobactam

• Registration Number: NCT06712641
• Lead Sponsor: University Hospital, Akershus

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-27
• Study First Submitted QC: 2024-11-27
• Study First Posted: 2024-12-02
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-27
• Last Update Posted: 2025-01-29
• Study Start: 2025-06
• Primary Completion: 2028-06
• Study Completion: 2033-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1940

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)
• Recent use of nephrotoxic drugs (e.g. cisplatin)
• Suspected or confirmed carrier of extended spectrum betalactamase (ESBL) producing bacteria
• Multiple myeloma
• Renal transplantation
• Myasthenia gravis
• Known hypersensitivity to any of the study drugs
• Pregnancy
• Any condition where gentamicin in the opinion of the investigator poses an unacceptable risk

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Gentamicin + narrow spectrum betalactam	Gentamicin + narrow spectrum betalactam	Empirical therapy for suspected community-acquired sepsis with gentamicin + narrow spectrum betalactam (either one of penicillin, ampicillin, or cloxacillin)
Cefotaxime or piperacillin-tazobactam	Piperacillin-tazobactam	Empirical therapy for suspected community-acquired sepsis with broad spectrum betalactam (either one of cefotaxime or piperacillin-tazobactam)
Cefotaxime or piperacillin-tazobactam	Cefotaxime	Empirical therapy for suspected community-acquired sepsis with broad spectrum betalactam (either one of cefotaxime or piperacillin-tazobactam)

Primary Outcome Measures

Name	Time	Method
30-day mortality	Up to 30 days after randomization	All-cause mortality up to 30 days after randomization
30-day acute kidney injury	Up to 30 days after randomization	Any acute kidney injury up to 30 days after randomization

Secondary Outcome Measures

Name	Time	Method
In-hospital mortality	During index hospitalization (commonly up to 30 days)	All-cause mortality during index hospitalization
Duration of hospital stay	During index hospitalization (commonly up to 30 days)	Duration of index hospitalization (days)
Duration of intensive care stay	During index hospitalization (commonly up to 30 days)	Duration of stay in intensive care unit (days)
Duration of ventilator therapy	During index hospitalization (commonly up to 30 days)	Duration of therapy with invasive mechanical ventilation (days)
Duration of vasopressor therapy	During index hospitalization (commonly up to 30 days)	Duration of therapy with vasoactive (vasopressor) (days)
Hospital readmissions	Up to 30 days after discharge from index hospitalization	Readmission after discharge from index hospitalization
Post-discharge mortality	Up to 30 days after discharge from index hospitalization	All-cause mortality after discharge from index hospitalization
Duration of antibiotic treatment	During index hospitalization (commonly up to 30 days)	Duration of antibiotic therapy during index hospitalization (days of therapy, DOT)
Gut microbiome composition	During index hospitalization (commonly up to 30 days)	Impact on the gut microbiome

Trial Locations

Locations (2)

Akershus University Hospital; 🇳🇴 Lørenskog, Norway

Oslo University Hospital Ullevål; 🇳🇴 Oslo, Norway