Article Text

Protocol
Short course antibiotic treatment of Gram-negative bacteraemia (GNB5): a study protocol for a randomised controlled trial
  1. Sandra Tingsgård1,
  2. Simone Bastrup Israelsen1,
  3. Louise Thorlacius-Ussing1,
  4. Karina Frahm Kirk2,
  5. Birgitte Lindegaard3,
  6. Isik S Johansen4,
  7. Andreas Knudsen5,
  8. Suzanne Lunding6,
  9. Pernille Ravn6,
  10. Christian Østergaard Andersen7,
  11. Thomas Benfield1
  1. 1Center of Research and Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
  2. 2Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
  3. 3Department of Pulmonary Medicine and Infectious Diseases, Copenhagen University Hospital - North Zealand, Hillerød, Denmark
  4. 4Department of Infectious Diseases, Odense Universitetshospital, Odense, Denmark
  5. 5Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark
  6. 6Department of Internal Medicine, Section for Infectious Diseases, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark
  7. 7Department of Clinical Microbiology, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
  1. Correspondence to Dr Sandra Tingsgård; sandra.tingsgaard{at}regionh.dk

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.

  • Infection control
  • Clinical trials
  • INFECTIOUS DISEASES
  • Clinical Trial
  • Urinary tract infections
http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

Footnotes

  • Twitter @STingsgard, @israelsen_sb

  • Contributors TB is the sponsor of the study. ST is the coordinating principal investigator. TB conceived the research question of the study. TB and ST obtained the funding for the study. TB, ST, SBI, LT-U and CØA participated in the design of the study. ST drafted the study protocol. TB, ST, SBI, LT-U, BL, ISJ, SL, CØA, PR, KFK and AK contributed to the implementation of the study and revised the protocol critically for important intellectual content. All authors read and approved the final manuscript.

  • Funding 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.

  • Disclaimer Sponsor and investigators are independent of economic or competing interests. Participants will not be financially reimbursed. Results from the study are only for scientific and public use and have no commercial interest.

  • 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.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.