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Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT

Ross, Jonathan D.C.; Harding, Jan; Duley, Lelia; Montgomery, Alan A; Hepburn, Trish; Tan, Wei; Brittain, Clare; Meakin, Garry; Sprange, Kirsty; Thandi, Sukhwinder; Jackson, Louise; Roberts, Tracy; Wilson, Janet; White, John; Dewsnap, Claire; Cole, Michelle; Lawrence, Tessa

Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT Thumbnail


Authors

Jonathan D.C. Ross

Jan Harding

Lelia Duley

ALAN MONTGOMERY ALAN.MONTGOMERY@NOTTINGHAM.AC.UK
Director Nottingham Clinical Trials Unit

TRISH HEPBURN Trish.Hepburn@nottingham.ac.uk
Senior Medical Statistician

Wei Tan

GARRY MEAKIN Garry.Meakin@nottingham.ac.uk
Senior Trial Manager

Sukhwinder Thandi

Louise Jackson

Tracy Roberts

Janet Wilson

John White

Claire Dewsnap

Michelle Cole

Tessa Lawrence



Abstract

Background: Gonorrhoea is a common sexually transmitted infection that can cause pain and discomfort, affect fertility in women and lead to epididymo-orchitis in men. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance reducing its effectiveness. Gentamicin is a potential alternative treatment requiring further evaluation. Objectives: To assess the clinical effectiveness and cost-effectiveness of gentamicin as an alternative
treatment to ceftriaxone in the treatment of gonorrhoea.

Design: A multicentre, parallel-group, blinded, non-inferiority randomised controlled trial.

Setting: Fourteen sexual health clinics in England. Participants: Adults aged 16–70 years with a diagnosis of uncomplicated, untreated genital, pharyngeal or rectal gonorrhoea based on a positive Gram-stained smear on microscopy or a positive nucleic acid
amplification test (NAAT).

Randomisation and blinding: Participants were randomised using a secure web-based system, stratified by clinic. Participants, investigators and research staff assessing participants were blinded to treatment allocation.

Interventions: Allocation was to either 240 mg of gentamicin (intervention) or 500 mg of ceftriaxone (standard treatment), both administered as a single intramuscular injection. All participants also received 1 g of oral azithromycin.

Main outcome measure: The primary outcome measure was clearance of Neisseria gonorrhoeae at all infected sites, confirmed by a negative Aptima Combo 2® (Hologic Inc., Marlborough, MA, USA) NAAT, at 2 weeks post treatment.

Results: We randomised 720 participants, of whom 81% were men. There were 358 participants in the gentamicin group and 362 in the ceftriaxone group; 292 (82%) and 306 (85%) participants, respectively, were included in the primary analysis. Non-inferiority of gentamicin to ceftriaxone could not be demonstrated
[adjusted risk difference for microbiological clearance –6.4%, 95% confidence interval (CI) –10.4% to –2.4%]. Clearance of genital infection was similar in the two groups, at 94% in the gentamicin group and 98% in the ceftriaxone group, but clearance of pharyngeal infection and rectal infection was lower in the gentamicin group (80% vs. 96% and 90% vs. 98%, respectively). Reported pain at the injection site was higher for gentamicin than for ceftriaxone. The side-effect profiles were comparable between the groups. Only one serious adverse event was reported and this was deemed not to be related to the trial medication. The economic analysis found that treatment with gentamicin is not cost neutral compared
with standard care, with average patient treatment costs higher for those allocated to gentamicin (£13.90, 95% CI £2.47 to £37.34) than to ceftriaxone (£6.72, 95% CI £1.36 to £17.84).

Limitations: Loss to follow-up was 17% but was similar in both treatment arms. Twelve per cent of participants had a negative NAAT for gonorrhoea at their baseline visit but this was balanced between treatment groups and unlikely to have biased the trial results.

Conclusions: The trial was unable to demonstrate non-inferiority of gentamicin compared with ceftriaxone in the clearance of gonorrhoea at all infected sites. Clearance at pharyngeal and rectal sites was lower for participants allocated to gentamicin than for those allocated to ceftriaxone, but was similar for genital sites
in both groups. Gentamicin was associated with more severe injection site pain. However, both gentamicin and ceftriaxone appeared to be well tolerated.

Future work: Exploration of the genetic determinants of antibiotic resistance in N. gonorrhoeae will help to identify accurate markers of decreased susceptibility. Greater understanding of the immune response to infection can assist gonococcal vaccine development.

Trial registration: Current Controlled Trials ISRCTN51783227.
Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 20.
See the NIHR Journals Library website for further project information.

Citation

Ross, J. D., Harding, J., Duley, L., Montgomery, A. A., Hepburn, T., Tan, W., …Lawrence, T. (2019). Gentamicin as an alternative to ceftriaxone in the treatment of gonorrhoea: the G-TOG non-inferiority RCT. Health Technology Assessment, 23(20), 1-104. https://doi.org/10.3310/hta23200

Journal Article Type Article
Acceptance Date May 1, 2019
Online Publication Date May 1, 2019
Publication Date May 1, 2019
Deposit Date Jun 25, 2019
Publicly Available Date Mar 29, 2024
Journal Health Technology Assessment
Print ISSN 1366-5278
Electronic ISSN 2046-4924
Publisher NIHR Journals Library
Peer Reviewed Not Peer Reviewed
Volume 23
Issue 20
Pages 1-104
DOI https://doi.org/10.3310/hta23200
Keywords Health Policy
Public URL https://nottingham-repository.worktribe.com/output/2226742
Publisher URL https://www.journalslibrary.nihr.ac.uk/hta/hta23200#/abstract

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