Aminoglycosides in Early Sepsis

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• 30-day mortality [Срок оценки: Up to 30 days after randomization]
• 30-day acute kidney injury [Срок оценки: Up to 30 days after randomization]

Вторичные конечные точки (8)

• In-hospital mortality [Срок оценки: During index hospitalization (commonly up to 30 days)]
• Duration of hospital stay [Срок оценки: During index hospitalization (commonly up to 30 days)]
• Duration of intensive care stay [Срок оценки: During index hospitalization (commonly up to 30 days)]
• Duration of ventilator therapy [Срок оценки: During index hospitalization (commonly up to 30 days)]
• Duration of vasopressor therapy [Срок оценки: During index hospitalization (commonly up to 30 days)]
• Hospital readmissions [Срок оценки: Up to 30 days after discharge from index hospitalization]
• Post-discharge mortality [Срок оценки: Up to 30 days after discharge from index hospitalization]
• Duration of antibiotic treatment [Срок оценки: During index hospitalization (commonly up to 30 days)]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Норвегия · 5 центров

• Haukeland University Hospital — Bergen
• Lovisenberg Diakonal Hospital — Oslo
• St. Olav's Hospital — Trondheim
• Akershus University Hospital — Lørenskog
• Oslo University Hospital Ullevål — Oslo

Идентификаторы

NCT: NCT06712641 · 2024-519797-39-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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