Cefixime Plus Doxycycline Compared to Ceftriaxone Plus Azithromycin for Treatment of Gonorrhoea
Condition: Gonorrhea
MeSH terms: Gonorrhea
Study type: Interventional
Phase: Phase 4

Summary: 
      A non-inferiority, open-label, multicentre randomised controlled trial to compare two
      therapeutic regimens for the treatment of uncomplicated urogenital, rectal or pharyngeal
      gonorrhoea in men and women between 18 and 75 years of age. Patients were enrolled and
      treated from April 2021 to June 2022 at the Dermatovenerology Department, University Hospital
      Bulovka, Prague, Czech Republic and the Venereology Prague, Medicentrum Beroun, Prague, Czech
      Republic.
    

Detailed description: 
      Non-inferiority, open-label, multicentre randomised clinical trial (RCT) compared two
      regimens for the treatment of uncomplicated urogenital, rectal or pharyngeal gonorrhoea in
      men and women between 18 and 65 years of age. Patients were enrolled and treated from April
      2021 to June 2022 at the Dermatovenerology Department, University Hospital Bulovka, Prague,
      and the Venereology Prague, Medicentrum Beroun, Prague, Czech Republic.

      Laboratory testing The diagnosis of gonorrhoea and C. trachomatis infection was established
      from urogenital, rectal and pharyngeal swab specimens. Laboratory testing for inclusion in
      the study and at 3 weeks after initiation of treatment was performed using the Cobas 4800
      CT/NG NAAT assay (Roche Diagnostics, Indianapolis, IN, USA). At test of cure visits 1 and 3
      weeks after the initiation of treatment, swabs for cultivation of N. gonorrhoeae were also
      sampled and immediately inoculated onto non-selective and selective Modified Thayer-Martin
      agar plates. Inoculated agar plates were directly transferred to the hospital laboratory for
      incubation at 36°C in a humid 5% CO2-enriched atmosphere for 48 hours. Suspected gonococcal
      colonies were species verified using the biochemical NEISSERIAtest® (LACHEMA, Brno, Czech
      Republic) or the PolyViteX VCAT3® medium (Biomérieux, Marcy l'Etoile, France).

      Statistical analyses Sample size was based on assessing non-inferiority of the cefixime plus
      doxycycline arm compared to the ceftriaxone plus azithromycin arm with a one-sided 5% type I
      error rate. We estimated the sample size based on estimates from other gonorrhoea treatment
      studies and expert opinions. The target sample size of 152 participants (76 per group) was
      based on an assumed treatment failure of 0% in the ceftriaxone-azithromycin arm and 2% in the
      cefixime-doxycycline arm, which would provide at least 90% power for the comparison of the
      primary endpoint. Intention-to-treat (ITT) and per-protocol analyses were done; per protocol
      results are reported here and ITT results in the online supplement. The ITT population was
      composed of all randomised patients; the per-protocol population consisted of patients who
      were randomised, received the allocated regimen (for doxycycline, at least ≥85% (12/14) of
      the prescribed dose) underwent follow-up examinations, and abstained from any sexual
      activities, including protected intercourse, during the study period. For each study group,
      the proportion of patients with urogenital, rectal or pharyngeal gonorrhoea who achieved
      microbiological cure was calculated. The Clopper-Pearson exact method was used to estimate
      confidence intervals (CIs). We used chi-square tests (Pearson's or Fisher's test when less
      than five observations) for binomial outcome measures and Student's t test for continuous
      outcome measures, as appropriate.
    

Intervention name(s): Cefixime; Doxycyclin; Ceftriaxon; Azithromycin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Two 400 mg tablets will be administered orally to equal a 800 mg dose.; One 100 mg tablet will be administered orally twice a day for 7 days; Dose of 1 g intramuscular one time; Four 500 mg tablets will be administered orally to equal a 2 g dose.
Other intervention name(s): Cefixime (ATC code J01DD08); Doxyhexal (ATC code J01AA02); Ceftriaxone (ATC code J01DD04); Sumamed (ATC code J01FA10)
Intervention MeSH terms: Azithromycin; Doxycycline; Ceftriaxone; Cefixime
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Patients were randomised to cefixime 800 mg single oral dose plus doxycycline 100 mg twice a day orally for 7 days or the comparator ceftriaxone 1 g single intramuscular dose plus azithromycin 2 g single oral dose with a computer-generated pseudo-random code using permuted block randomisation in a 1:1 ratio
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neisseria gonorrhoeae; Cefixime; Azithromycin; Ceftriaxone; Doxycycline