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

NCT ID: NCT06090565

Last Updated: 2023-10-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2022-12-22

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.

Conditions

Gonorrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Cefixime plus doxycycline

Single-dose cefixime 800 mg plus doxycycline 100 mg b.i.d. for 7 days

Group Type: EXPERIMENTAL

Cefixime

Intervention Type: DRUG

Two 400 mg tablets will be administered orally to equal a 800 mg dose.

Doxycyclin

Intervention Type: DRUG

One 100 mg tablet will be administered orally twice a day for 7 days

Ceftriaxone plus azithromycin

Single dose ceftriaxone 1 g plus single-dose azithromycin 2 g

Group Type: ACTIVE_COMPARATOR

Ceftriaxon

Intervention Type: DRUG

Dose of 1 g intramuscular one time

Azithromycin

Intervention Type: DRUG

Four 500 mg tablets will be administered orally to equal a 2 g dose.

Interventions

Cefixime

Two 400 mg tablets will be administered orally to equal a 800 mg dose.

Intervention Type: DRUG

Doxycyclin

One 100 mg tablet will be administered orally twice a day for 7 days

Intervention Type: DRUG

Ceftriaxon

Dose of 1 g intramuscular one time

Intervention Type: DRUG

Azithromycin

Four 500 mg tablets will be administered orally to equal a 2 g dose.

Intervention Type: DRUG

Other Intervention Names

Cefixime (ATC code J01DD08); Doxyhexal (ATC code J01AA02); Ceftriaxone (ATC code J01DD04); Sumamed (ATC code J01FA10)

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Örebro University, Sweden

OTHER

Sponsor Role: collaborator

Bulovka Hospital

OTHER

Sponsor Role: lead

Responsible Party

Filip Rob MD, PhD

Head of Dermatovenereology Dept.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Filip Rob, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Nemocnice Na Bulovce

Locations

Venereology Prague, Medicentrum Beroun

Prague, , Czechia

University Hospital Bulovka

Prague, , Czechia

Countries

Czechia

Other Identifiers

9937

Identifier Type: -

Identifier Source: org_study_id