Aminoglycosides in Early Sepsis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Gentamicin + narrow spectrum betalactam, Cefotaxime, Piperacillin-tazobactam.
- Who it may be relevant to
- Registry conditions: Sepsis. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Norway
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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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
Overview
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.
Interventions
- Drug Gentamicin + narrow spectrum betalactam
Empirical therapy for suspected community-acquired sepsis with gentamicin + narrow spectrum betalactam (either one of penicillin, ampicillin, or cloxacillin) - Drug Cefotaxime
Empirical therapy for suspected community-acquired sepsis with cefotaxime - Drug Piperacillin-tazobactam
Empirical therapy for suspected community-acquired sepsis with piperacillin-tazobactam
Primary outcome measures
- 30-day mortality [Time frame: Up to 30 days after randomization]
- 30-day acute kidney injury [Time frame: Up to 30 days after randomization]
Secondary outcome measures (8)
- In-hospital mortality [Time frame: During index hospitalization (commonly up to 30 days)]
- Duration of hospital stay [Time frame: During index hospitalization (commonly up to 30 days)]
- Duration of intensive care stay [Time frame: During index hospitalization (commonly up to 30 days)]
- Duration of ventilator therapy [Time frame: During index hospitalization (commonly up to 30 days)]
- Duration of vasopressor therapy [Time frame: During index hospitalization (commonly up to 30 days)]
- Hospital readmissions [Time frame: Up to 30 days after discharge from index hospitalization]
- Post-discharge mortality [Time frame: Up to 30 days after discharge from index hospitalization]
- Duration of antibiotic treatment [Time frame: During index hospitalization (commonly up to 30 days)]
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Norway · 5 centers
- Haukeland University Hospital — Bergen
- Lovisenberg Diakonal Hospital — Oslo
- St. Olav's Hospital — Trondheim
- Akershus University Hospital — Lørenskog
- Oslo University Hospital Ullevål — Oslo
Identifiers
NCT: NCT06712641 · 2024-519797-39-00