TY - JOUR

T1 - Short course antibiotic treatment of Gram-negative bacteraemia (GNB5)

T2 - A study protocol for a randomised controlled trial

AU - Tingsgård, Sandra

AU - Israelsen, Simone Bastrup

AU - Thorlacius-Ussing, Louise

AU - Frahm Kirk, Karina

AU - Lindegaard, Birgitte

AU - Johansen, Isik S.

AU - Knudsen, Andreas

AU - Lunding, Suzanne

AU - Ravn, Pernille

AU - Østergaard Andersen, Christian

AU - Benfield, Thomas

N1 - Funding Information: The study is partly financially supported by a grant from Hvidovre Hospital Strategic Research Fund, Danish Regions Medicine Grant, grant number EMN-2019-01055, and Capital Region of Denmark Research Fund, grant number A6688. Additional federal funding will be sought. Study participants and the Research Ethics Committee of the Capital Region of Denmark will be informed if additional funding has been granted. Publisher Copyright: © 2023 BMJ Publishing Group. All rights reserved.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Clinical Trial

KW - Clinical trials

KW - Infection control

KW - INFECTIOUS DISEASES

KW - Urinary tract infections

U2 - 10.1136/bmjopen-2022-068606

DO - 10.1136/bmjopen-2022-068606

M3 - Journal article

C2 - 37156588

AN - SCOPUS:85158123728

VL - 13

JO - BMJ Open

JF - BMJ Open

SN - 2044-6055

IS - 5

M1 - e068606

ER -