New AntiBiotic Treatment Options for Uncomplicated Anogenital GOnorrhoea
- Conditions
- Gonorrhea
- Interventions
- Registration Number
- NCT03294395
- Lead Sponsor
- Public Health Service of Amsterdam
- Brief Summary
This study evaluates the efficacy of three experimental antibiotics in the treatment of uncomplicated anogenital gonorrhoea. Participants will be randomized to one of four study arms and will receive either one of the three experimental antibiotics (ertapenem, fosfomycin and gentamicin) or the current standard antibiotic (ceftriaxone). Both the study team and the participant are blinded to the administered treatment. This enables the investigators to compare the eradication capacity and safety of the experimental antibiotics with the standard treatment.
\*Following the advise of the DSMB based on a planned interim analysis, in October 2018 one study arm (fosfomycin 6g PO) was dropped and the randomized clinical trial was continued with three treatment arms (ceftriaxone 500mg IM, ertapenem 1000mg IM and gentamicin 5mg/kg IM) and without the oral placebo.
- Detailed Description
Antimicrobial resistance (AMR) to extended spectrum cephalosporins (ESC) among Neisseria gonorrhoeae (Ng) is a major public health concern. With no alternative antimicrobial treatment options for gonorrhoea and only a few new drugs in the development pipeline, it is important to test existing antibiotics for their efficacy in gonorrhoea treatment. This project aims to identify new treatment modalities for uncomplicated gonorrhoea using the registered drugs ertapenem, fosfomycin and gentamicin. This trial is a double blind randomized clinical non-inferiority trial with four treatment arms. 108 participants are randomly assigned to each study arm . Participants will receive either ceftriaxone 500mg intramuscularly (IM) or ertapenem 1000mg IM or gentamicin 5mg/kg IM with a maximum of 400mg (in two doses) supplemented with an oral placebo, or receive fosfomycin 6g oral suspension supplemented with an intramuscular placebo. The bacterial eradication capacity of the study antimicrobials at the included infection site is measured 7-14 days after treatment, using an RNA-based Nucleic Acid Amplification Test (NAAT).
\*Following the advise of the DSMB based on a planned interim analysis, in October 2018 one study arm (fosfomycin 6g PO) was dropped and the randomized clinical trial was continued with three treatment arms (ceftriaxone 500mg IM, ertapenem 1000mg IM and gentamicin 5mg/kg IM) and without the oral placebo.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 346
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Gentamicin im Gentamicin Sulfate, Injectable Gentamicin sulfate, injectable 5mg/kg (single intramuscular dose) + placebo (single oral dose) Ertapenem im Ertapenem 1000 MG Ertapenem 1000mg (single intramuscular dose) + placebo (single oral dose) Fosfomycin po Fosfomycin Oral Suspension Fosfomycin oral suspension 6g (single oral dose) + placebo (single intramuscular dose) Ceftriaxone im Ceftriaxone Current standard treatment. Ceftriaxone 500mg (single intramuscular dose) + placebo (single oral dose)
- Primary Outcome Measures
Name Time Method Proportion of participants with treatment success in each study arm for the included anatomic infection 7-14 days after treatment Proportion of participants with treatment success in each study arm using a molecular test (Nucleic acid amplification test, NAAT). Treatment succes is defined as a negative test of cure (NAAT) 7-14 days after treatment.
- Secondary Outcome Measures
Name Time Method Blood plasma concentration of ceftriaxone, ertapenem and gentamicin in a subset of 60 NABOGO participants within 24 hours after treatment administration The blood plasma concentration will be measured 1 times within the first 24 hours after treatment administration. With these measurements the investigators will estimate the population pharmacokinetics of ceftriaxone, ertapenem and gentamicin.
Antimicrobial susceptibility of Ng-strains to study antibiotics Day 0 (before treatment) - 28 (after treatment) The in vitro antimicrobial susceptibility (in MIC) of the experimental and reference treatment will be measured in all Ng strains collected at all infected anatomical sites of each participant at inclusion and in case of a positive test of cure.
Proportion of participants with treatment success in each study arm at all anatomical infection sites 7-28 days after treatment Proportion of participants with treatment success in each study arm using a molecular test (Nucleic acid amplification test, NAAT). Treatment succes is defined as a negative test of cure (NAAT) 7-28 days after treatment.
Clinical and demographic predictors for treatment failure until 7-14 days after treatment The investigators will measure if demographic (e.g. gender, HIV status) and clinical factors (e.g. anatomical location, duration of symptoms before treatment) are associated with treatment failure (treatment failure is defined as any case in which the participant received escape medication).
Incidence of treatment-emergent adverse events until 30 days after treatment The incidence, type and severity of treatment-related adverse events as assessed by CTCAE v4.0 will be measured.
Duration of symptoms after treatment 1-30 days after treatment All participants are asked to report their symptoms daily in a diary, this will be evaluated at the follow-up visit (7-14 days after treatment) and at the online evaluation questionnaire (30 days after treatment). The mean duration of all symptoms after treatment will be measured for all study antibiotics.
Blood plasma concentration of ceftriaxone, ertapenem and fosfomycin in 60 healthy volunteers 24 hours Healthy volunteers will be randomly assigned to one of the three antibiotics. After administration of the antibiotic, the blood plasma concentration will be measured 4 times within the first 24 hours. With these measurements the investigators will estimate the population pharmacokinetics of ceftriaxone, ertapenem and fosfomycin.
Trial Locations
- Locations (1)
Public Health Service
🇳🇱Amsterdam, Noord Holland, Netherlands