Clinical trial NCT06712641: Aminoglycosides in Early Sepsis
Official title: Aminoglycosides in Early Sepsis (AGES): A Randomized Pragmatic Clinical Trial Comparing Gentamicin and Narrow Spectrum Betalactams to Broad Spectrum Betalactams as Empirical Treatment in Patients With Suspected Sepsis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Sepsis
Keywords: sepsis
antibiotics
aminoglycosides
cephalosporins
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
Collaborators: name: Ullevaal University Hospital
First posted: 2024-12-02
Enrollment: 1940
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)
* 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

Primary outcomes:
measure: 30-day mortality
timeFrame: Up to 30 days after randomization
measure: 30-day acute kidney injury
timeFrame: Up to 30 days after randomization
Secondary outcomes:
measure: In-hospital mortality
timeFrame: During index hospitalization (commonly up to 30 days)
measure: Duration of hospital stay
timeFrame: During index hospitalization (commonly up to 30 days)
measure: Duration of intensive care stay
timeFrame: During index hospitalization (commonly up to 30 days)
measure: Duration of ventilator therapy
timeFrame: During index hospitalization (commonly up to 30 days)
measure: Duration of vasopressor therapy
timeFrame: During index hospitalization (commonly up to 30 days)
measure: Hospital readmissions
timeFrame: Up to 30 days after discharge from index hospitalization
measure: Post-discharge mortality
timeFrame: Up to 30 days after discharge from index hospitalization
measure: Duration of antibiotic treatment
timeFrame: During index hospitalization (commonly up to 30 days)
measure: Gut microbiome composition
timeFrame: During index hospitalization (commonly up to 30 days)
Other outcomes:
Locations:
city: Lørenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital Ullevål
Study officials:
References: