Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial

• Published in: Current controlled trials in cardiovascular medicine Vol. 17; no. 1; p. 558
• Main Authors: Brittain, Clare, Childs, Margaret, Duley, Lelia, Harding, Jan, Hepburn, Trish, Meakin, Garry, Montgomery, Alan A, Tan, Wei, Ross, Jonathan D C
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 24.11.2016; BioMed Central
• Subjects: Administration, Oral; Adolescent; Adult; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - economics; Antibiotics; Azithromycin - administration & dosage; Ceftriaxone; Ceftriaxone - administration & dosage; Ceftriaxone - adverse effects; Ceftriaxone - economics; Ceftriaxone sodium; Clinics; Comparative analysis; Cost-Benefit Analysis; Drug Costs; Drug Resistance, Bacterial; Drug therapy; Drug Therapy, Combination; England; Female; Gentamicin; Gentamicins - administration & dosage; Gentamicins - adverse effects; Gentamicins - economics; Gonorrhea; Gonorrhea - diagnosis; Gonorrhea - drug therapy; Gonorrhea - economics; Gonorrhea - microbiology; Humans; Hypotheses; Infections; Inflammatory diseases; Injections, Intramuscular; Laboratories; Male; Microbial Sensitivity Tests; Middle Aged; Minority & ethnic groups; Pelvic inflammatory disease; Remission Induction; Research Design; Sexual health; Sexually transmitted diseases; STD; Study Protocol; Time Factors; Treatment Outcome; Womens health; Young Adult; United Kingdom > UK; England; Resistance; Gonorrhoea; Treatment; Gentamicin; Randomised trial; Noninferiority; Ceftriaxone
• ISSN: 1745-6215; 1745-6215
• DOI: 10.1186/s13063-016-1683-8

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.