New AntiBiotic Treatment Options for Uncomplicated Anogenital GOnorrhoea

NCT03294395 | Completed Phase 3 DMC

• 1 other identifier: NABOGO
• Study Type: interventional
• Target: 346
• Locations: 1 country
• Sites: 1

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.

Conditions

Gonorrhea

Keywords

Antimicrobial resistance; Antibiotics; Fosfomycin; Ertapenem; Gentamicin; Neisseria Gonorrhoeae

Outcome Measures

Primary Outcomes (1)

• Proportion of participants with treatment success in each study arm for the included anatomic infection

  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.

  7-14 days after treatment

Secondary Outcomes (7)

• Proportion of participants with treatment success in each study arm at all anatomical infection sites

  7-28 days after treatment

• Incidence of treatment-emergent adverse events

  until 30 days after treatment

• Antimicrobial susceptibility of Ng-strains to study antibiotics

  Day 0 (before treatment) - 28 (after treatment)

• Blood plasma concentration of ceftriaxone, ertapenem and gentamicin in a subset of 60 NABOGO participants

  within 24 hours after treatment administration

• Duration of symptoms after treatment

  1-30 days after treatment

Study Arms (4)

Ceftriaxone im

ACTIVE COMPARATOR

Current standard treatment. Ceftriaxone 500mg (single intramuscular dose) + placebo (single oral dose)

Drug: Ceftriaxone

Ertapenem im

EXPERIMENTAL

Ertapenem 1000mg (single intramuscular dose) + placebo (single oral dose)

Drug: Ertapenem 1000 MG

Fosfomycin po

EXPERIMENTAL

Fosfomycin oral suspension 6g (single oral dose) + placebo (single intramuscular dose)

Drug: Fosfomycin Oral Suspension

Gentamicin im

EXPERIMENTAL

Gentamicin sulfate, injectable 5mg/kg (single intramuscular dose) + placebo (single oral dose)

Drug: Gentamicin Sulfate, Injectable

Interventions

Ertapenem 1000 MG DRUG

single dose 1000mg intramuscular injection

Also known as: Invanz

Ertapenem im

Fosfomycin Oral Suspension DRUG

single dose 6g oral suspension

Also known as: Monuril

Fosfomycin po

Gentamicin Sulfate, Injectable DRUG

single dose 5mg/kg (maximum 400mg) intramuscular injection

Also known as: no other names

Gentamicin im

Ceftriaxone DRUG

single dose 500mg intramuscular injection

Also known as: no other names

Ceftriaxone im

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Anorectal, cervical/vaginal or urethral Ng infection, diagnosed by the following:
• Ng-positive Gram-stained smear (intracellular Gram-negative diplococci and leukocytes) and/or
• Positive for Ng by nucleic acid amplification test (NAAT) (Aptima Combo 2) and/or
• Positive for Ng by culture
• 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

You may not qualify if:

• 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
• Not able to read/understand Dutch or English
• HIV infection if:
• CD4+ cell-count \<200 cells/μL (as reported by the patient)
• 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:
• systemic antibacterial antimicrobials other than nitrofurantoin or metronidazole
• systemic immunosuppressive drugs

Sponsors & Collaborators

• Public Health Service of Amsterdam: lead
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator

Study Sites (1)

Public Health Service

Amsterdam, North Holland, 1018WT, Netherlands

Location

Related Publications (3)

• Teker B, Schim van der Loeff M, Boyd A, Mathot R, van Dam A, de Vries H, Jongen VW. Diarrhoea as a frequent adverse event after intramuscular ertapenem treatment for uncomplicated Neisseria gonorrhoeae: a secondary analysis from the NABOGO trial. Sex Transm Infect. 2026 Jan 16:sextrans-2025-056735. doi: 10.1136/sextrans-2025-056735. Online ahead of print.

  PMID: 41545057 DERIVED

• Teker B, de Vries H, Heijman T, van Dam A, Schim van der Loeff M, Jongen VW. Spontaneous clearance of asymptomatic anogenital and pharyngeal Neisseria gonorrhoeae: a secondary analysis from the NABOGO trial. Sex Transm Infect. 2023 Jun;99(4):219-225. doi: 10.1136/sextrans-2022-055488. Epub 2022 Jul 12.

  PMID: 35820778 DERIVED

• de Vries HJC, de Laat M, Jongen VW, Heijman T, Wind CM, Boyd A, de Korne-Elenbaas J, van Dam AP, Schim van der Loeff MF; NABOGO steering group. Efficacy of ertapenem, gentamicin, fosfomycin, and ceftriaxone for the treatment of anogenital gonorrhoea (NABOGO): a randomised, non-inferiority trial. Lancet Infect Dis. 2022 May;22(5):706-717. doi: 10.1016/S1473-3099(21)00625-3. Epub 2022 Jan 19.

  PMID: 35065063 DERIVED

MeSH Terms

Conditions

Gonorrhea

Interventions

Ertapenem; Fosfomycin; Gentamicins; Injections; Ceftriaxone

Condition Hierarchy (Ancestors)

Neisseriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Sexually Transmitted Diseases; Communicable Diseases; Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Organophosphonates; Organophosphorus Compounds; Aminoglycosides; Glycosides; Carbohydrates; Drug Administration Routes; Drug Therapy; Therapeutics; Cefotaxime; Cephacetrile; Cephalosporins; Thiazines; Sulfur Compounds

Study Officials

• Henry JC de Vries, PhD, MD

  Public Health Service of Amsterdam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants receive either intramuscular treatment and if applicable intramuscular placebo. Both particpant and care provider are blind to the regimen.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor MD, PhD

Model Details: A double-blind randomized clinical trial with non-inferiority design \*since October 2018 one study arm (fosfomycin) has been dropped. In a subset of these participants the plasma concentration of ceftriaxone, ertapenem and gentamicin is measured. An open-label randomized substudy evaluating the pharmacokinetics of ceftriaxone ertapenem and fosfomycin in 60 healthy volunteers (this number is in addition to the 346 NABOGO participants with gonorrhea)

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 27, 2017
• Study Start: September 18, 2017
• Primary Completion: June 5, 2020
• Study Completion: June 5, 2020
• Last Updated: August 6, 2021

Record last verified: 2021-07

Locations

NL (1)