title: Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.
abstract: Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea.
  
  
  
  This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness.
  
  
  
  The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate whether gentamicin is not clinically worse than ceftriaxone for the treatment of gonorrhoea. This will inform clinical practice and policy for the treatment of gonorrhoea when current therapy with cephalosporins is no longer effective, or is contraindicated.
  
  
  
  International Standard Randomised Controlled Trial Number - ISRCTN51783227 , Registered on 18 September 2014. Current protocol version 2.0 17 June 2015.
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Brittain
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Margaret
authors.initials: M
authors.lastname: Childs
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Lelia
authors.initials: L
authors.lastname: Duley
authors.affiliation: University Hospitals Birmingham NHS Foundation Trust, Whittall Street Clinic, Whittall Street, Birmingham, B4 6DH, UK.
authors.forename: Jan
authors.initials: J
authors.lastname: Harding
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Trish
authors.initials: T
authors.lastname: Hepburn
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Garry
authors.initials: G
authors.lastname: Meakin
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Montgomery
authors.affiliation: Nottingham Clinical Trials Unit, Nottingham Health Science Partners, Queen's Medical Centre, C Floor South Block, Nottingham, NG7 2UH, UK.
authors.forename: Wei
authors.initials: W
authors.lastname: Tan
authors.affiliation: University Hospitals Birmingham NHS Foundation Trust, Whittall Street Clinic, Whittall Street, Birmingham, B4 6DH, UK. jonathan.ross@uhb.nhs.uk.
authors.forename: Jonathan D C
authors.initials: JD
authors.lastname: Ross
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D017963:Azithromycin / Q000008:administration & dosage; D002443:Ceftriaxone / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D003362:Cost-Benefit Analysis; D016527:Drug Costs; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004739:England; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D006069:Gonorrhea / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012074:Remission Induction; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D002443:Ceftriaxone; D017963:Azithromycin
keywords: Ceftriaxone; Gentamicin; Gonorrhoea; Noninferiority; Randomised trial; Resistance; Treatment