Status and phase
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About
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.
Full 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.
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
Inclusion criteria main study
18 years or older
Anorectal, cervical/vaginal or urethral Ng infection, diagnosed by the following:
Provide samples from the included infection site for NAAT and direct culture immediately before treatment
Willing to abstain from anal, vaginal and oral sex until the test of cure (TOC)-visit, or use condoms during sex
Willing and able to return for a TOC-visit 7-14 days after treatment
Provide informed consent
Accept intramuscular injections
Exclusion criteria main study
Pre-randomisation:
Suspicion of a complicated Ng infection based on signs and/or symptoms indicating pelvic inflammatory disease (PID), epididymitis, prostatitis or gonococcal arthritis*
Another (sexually transmitted) infection or a suspicion of another infection for which systemic antimicrobial therapy is indicated
Pregnancy, having a wish to become pregnant or breastfeeding (tested at inclusion visit)
Not able to read/understand Dutch or English
HIV infection if:
Known allergy or adverse reactions to ceftriaxone, ertapenemor gentamicin
Known renal impairment (based on estimated GFR using Cockroft and Gault formula using serum creatinin measured with a point-of-care (POC) test; cut off value renal impairment eGFR ≤ 50 ml/min)
Known liver cirrhosis (based on history)
Known congestive heart failure (based on history)
Known myasthenia gravis
Known hearing loss or balance disorder, confirmed by an ear-nose-throat (ENT)-doctor or for which an ENT doctor has been consulted and a diagnostic process is still in progress (based on history)
Concurrent use of any of the following medication:
Use of any antimicrobial therapy other than nitrofurantoin or metronidazole in the two weeks prior to study enrollment (based on history)
Previous enrollment in the study
Concurrent participation in other non-observational medical research*
Unlikely to adhere to the study protocol
Post-randomisation:
Exclusion of participants from the modified intention to treat analysis (mITT):
Negative result of Ng NAAT of sample collected on T0 (the day of treatment). This could be the case in the following situations:
Loss to follow-up, i.e. no study visit TOC 7-14 days after treatment administration.
Exclusion from per protocol analysis (PP):
Inclusion criteria PK substudy (healthy volunteers):
Exclusion criteria PK substudy (healthy volunteers)
Pre-randomisation:
Pregnancy, having a wish to become pregnant or breastfeeding (tested at inclusion visit)
Not able to read/understand Dutch or English
Known allergy or adverse reactions to ceftriaxone, ertapenem, or fosfomycin.
Known renal impairment (based on estimated GFR using Cockroft and Gault formula using serum creatinin measured with a point-of-care (POC) test; cut off value renal impairment eGFR ≤ 50 ml/min)
Known liver cirrhosis (based on history)
Concurrent use of any of the following medication:
Use of any systemic antimicrobial therapy other than nitrofurantoin or metronidazole in the two weeks prior to study enrollment (based on history)
Concurrent participation in other non-observational medical research (apart from NABOGO RCT)
Unlikely to adhere to the study
Primary purpose
Allocation
Interventional model
Masking
346 participants in 4 patient groups
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Data sourced from clinicaltrials.gov
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