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. 2023 May 8;13(5):e068606.
doi: 10.1136/bmjopen-2022-068606.

Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial

Sandra Tingsgård  1 , Simone Bastrup Israelsen  2 , Louise Thorlacius-Ussing  2 , Karina Frahm Kirk  3 , Birgitte Lindegaard  4 , Isik S Johansen  5 , Andreas Knudsen  6 , Suzanne Lunding  7 , Pernille Ravn  7 , Christian Østergaard Andersen  8 , Thomas Benfield  2
Affiliations

Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial

Sandra Tingsgård et al. BMJ Open. .

Abstract

Introduction: Prolonged use of antibiotics is closely related to antibiotic-associated infections, antimicrobial resistance and adverse drug events. The optimal duration of antibiotic treatment for Gram-negative bacteremia (GNB) with a urinary tract source of infection is poorly defined.

Methods and analysis: Investigator-initiated multicentre, non-blinded, non-inferiority randomised controlled trial with two parallel treatment arms. One arm will receive shortened antibiotic treatment of 5 days and the other arm will receive antibiotic treatment of 7 days or longer. Randomisation will occur in equal proportion (1:1) no later than day 5 of effective antibiotic treatment as determined by antibiogram. Immunosuppressed patients and those with GNB due to non-fermenting bacilli (Acinetobacter spp, Pseudomonas spp), Brucella spp, Fusobacterium spp or polymicrobial growth are ineligible.The primary endpoint is 90-day survival without clinical or microbiological failure to treatment. Secondary endpoints include all-cause mortality, total duration of antibiotic treatment, hospital readmission and Clostridioides difficile infection. Interim safety analysis will be performed after the recruitment of every 100 patients. Given an event rate of 12%, a non-inferiority margin of 10%, and 90% power, the required sample size to determine non-inferiority is 380 patients. Analyses will be performed on both intention-to-treat and per-protocol populations.

Ethics and dissemination: The study is approved by the Danish Regional Committee on Health Research (H-19085920) and the Danish Medicines Agency (2019-003282-17). The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.

Trial registration number: ClinicalTrials.Gov:NCT04291768.

Keywords: Clinical Trial; Clinical trials; INFECTIOUS DISEASES; Infection control; Urinary tract infections.

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Conflict of interest statement

Competing interests: TB reports grants from Novo Nordisk Foundation, Lundbeck Foundation, Simonsen Foundation, GSK, Pfizer, Gilead, Kai Hansen Foundation and Erik and Susanna Olesen’s Charitable Fund; personal fees from GSK, Pfizer, Boehringer Ingelheim, Gilead, MSD, Pentabase ApS, Becton Dickinson, Janssen and Astra Zeneca; outside the submitted work. The remaining authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Flow chart on study level.
Figure 2
Figure 2
Flow chart on participant level.
See this image and copyright information in PMC

References

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