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Cefixime Plus Doxycycline Compared to Ceftriaxone Plus Azithromycin for Treatment of Gonorrhoea

Phase 4
Completed
Conditions
Gonorrhea
Interventions
Registration Number
NCT06090565
Lead Sponsor
Bulovka Hospital
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
161
Inclusion Criteria
  • uncomplicated urogenital, rectal or pharyngeal gonorrhoea diagnosed using the nucleic acid amplification test
Exclusion Criteria
  • any antimicrobial treatment during the 4 weeks before study enrolment
  • pregnancy or lactation
  • autoimmune disease
  • renal, hepatic or cardiac insufficiency
  • immunosuppressive therapy
  • allergy to cephalosporins, macrolides or doxycycline

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ceftriaxone plus azithromycinCeftriaxonSingle dose ceftriaxone 1 g plus single-dose azithromycin 2 g
Cefixime plus doxycyclineCefiximeSingle-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days
Cefixime plus doxycyclineDoxycyclinSingle-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days
Ceftriaxone plus azithromycinAzithromycinSingle dose ceftriaxone 1 g plus single-dose azithromycin 2 g
Primary Outcome Measures
NameTimeMethod
Number of Participants with negative cultures 1 and 3 weeks and a negative NAAT 3 weeks (±3 days) after treatment initiation.One and three weeks (±3 days)

To assess the eradication rate of Neisseria gonorrhoeae by culture and NAAT following a single-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days compared to single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g (Intent to Treat population).

Secondary Outcome Measures
NameTimeMethod
Occurrence of treatment-related severe adverse events in treatment groupsOne and three weeks (±3 days)

Adverse event frequency and severity will be compared between patients who received single-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days compared to single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g

Number of Participants with clinical cure defined as disappearance of clinical symptoms and signs 1 week after treatment according to the clinical assessment of the patient by the physician.One week (±3 days)

To assess clinical cure (disapperance of clinical symptoms and sings) following a single-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days compared to single-dose ceftriaxone 1 g plus single-dose azithromycin 2 g (Intent to Treat population).

Trial Locations

Locations (2)

University Hospital Bulovka

🇨🇿

Prague, Czechia

Venereology Prague, Medicentrum Beroun

🇨🇿

Prague, Czechia

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