A single injection of gentamicin, an older antibiotic, is being tested head-to-head against the current standard treatment, ceftriaxone, to see if it can cure gonorrhoea just as well. This matters because *Neisseria gonorrhoeae* is rapidly developing resistance to ceftriaxone, the last reliably effective antibiotic for the infection. The UK has few backup options. If gentamicin proves non-inferior, clinicians gain a second, effective first-line drug, reducing the pressure that drives resistance against ceftriaxone alone. The trial will recruit 718 patients across seven sexual health clinics in England. Participants receive either a 240 mg injection of gentamicin or a 500 mg injection of ceftriaxone, both with a single oral dose of azithromycin. The primary measure is a negative test for the bacteria two weeks after treatment. If successful, this would directly change clinical guidelines for treating gonorrhoea, offering a safe, cost-neutral alternative that could extend the useful life of both antibiotics. It addresses a quiet but serious public health threat: the gradual erosion of effective treatments for a common sexually transmitted infection.
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Design: A multi-centre, parallel group, blinded, randomised controlled trial, with equal allocation [1:1]. Setting: The trial will take place in sexual health outpatient clinics in Birmingham, Leeds, London (3 centres), Manchester, Sheffield and Southampton. Target Population: Men and women aged 16-70 with a diagnosis of genital, pharyngeal or rectal gonorrhoea. Eligibility Criteria: Inclusion • men and women aged 16-70 • diagnosis of untreated genital, pharyngeal or rectal gonorrhoea based on a positive gram stained smear on microscopy, or positive nucleic acid amplification test (NAAT) • written informed consent Exclusion • concurrent bacterial sexually transmitted infection (except for chlamydia) • known contra-indications or allergy to gentamicin, ceftriaxone or azithromycin • pregnancy or breastfeeding • complicated gonorrhoea infections e.g. pelvic inflammatory disease, epididymo-orchitis • need for concurrent additional antibiotic therapy • weight less than 40kg • received ceftriaxone or gentamicin within the preceding 28 days Health Technologies being assessed: Ceftriaxone is the current accepted therapy for gonorrhoea and recommended in the British Association for Sexual Health and HIV guidelines (www.bashh.org). Azithromycin is given with ceftriaxone to provide antimicrobial cover for Chlamydia trachomatis, which occurs as a co-infection in 30% of patients with gonorrhoea, and to also provide additional antimicrobial activity against N. gonorrhoeae. Azithromycin is not recommended as monotherapy for gonorrhoea due to the risk of resistance rapidly developing and poor tolerability of the higher dose required (2g). The health technology being assessed is gentamicin in comparison to ceftriaxone for the treatment of gonorrhoea. Participants will be randomised to receive either a single intramuscular injection of gentamicin (240mg) OR single intramuscular injection of ceftriaxone (500mg). Additionally both groups will receive a single oral dose of azithromycin (1g). Participants will be blinded to which therapy they receive. Measurement of costs and outcomes: The primary outcome measure is clearance of N. gonorrhoeae at the infected site confirmed by a negative nucleic acid amplification test, two weeks post treatment (as recommended by the British Association for Sexual Health and HIV). Secondary outcomes are clinical resolution of symptoms, frequency of adverse events and tolerability of therapy. Laboratory assessment of antibiotic resistance will be performed by measuring minimum inhibitory concentrations (MICs) to assess what concentration of antibiotic is required to completely inhibit bacterial growth. Isolate MICs will be measured using the serial agar dilution method. The economic analysis will compare the costs associated with the current standard treatment, ceftriaxone, with those of the proposed alternative treatment, gentamicin, in the treatment of gonorrhoea. Given that the primary objective of the trial is to determine non-inferiority of gentamicin, the economic analysis will focus on establishing whether the use of gentamicin rather than ceftriaxone is cost-neutral in the treatment of gonorrhoea. Sample size: Based on an efficacy rate of 96% for the ceftriaxone regimen which is consistent with previous treatment trials a total sample size of 646 (323 in each group) will achieve 90% power to detect non-inferiority with lower confidence interval of 5% using a one-sided binomial test for non-inferiority. The significance level is 0.0250. To allow for a loss to follow up rate of up to 10%, the study will recruit a total of 718 patients. A 5% lower confidence interval was acceptable to 17 of 24 sexual health patients whose opinion was sought and provides a realistic recruitment target. Project timetable including recruitment rate: Months -6-0: the first 6 months will be dedicated to the trial set-up including negotiating contracts, producing all study do
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