500-mg Versus 1000-mg Ceftriaxone for Uncomplicated Gonorrhea Infection

This is a noninferiority randomized controlled trial to compare the treatment effect of 500-mg to 1000-mg of ceftriaxone for uncomplicated gonorrhea infection in men.

• ceftriaxone 500-mg (Drug): single-dose ceftriaxone 500-mg intramuscular injection, dissolved in 2 mL of 1% lidocaine hydrochloride solution
• ceftriaxone 1000-mg (Drug): single-dose ceftriaxone 1000-mg intramuscular injection, dissolved in 3.5 mL of 1% lidocaine hydrochloride solution

Primary outcomes

• Treatment response of UGI [From enrollment to 14 days after treatment]: The proportion of participants with successful treatment of UGI, defined as a NAAT-negative and, if applicable, a culture-negative result of the primary anatomic sites of infection 7-14 days after treatment; a culture-negative result is required only if N. gonorrhoeae culture was positive at the screening visit.

Secondary outcomes

• Symptom duration [From enrollment to 14 days after treatment]: Symptom duration, including dysuria, genital discharge, sore throat, anorectal pain, rectal bleeding, and rectal discharge, in the subgroup of patients who have baseline symptoms attributable to UGIs.
• Treatment-related adverse events [From enrollment to 14 days after treatment]: Treatment-related adverse events until 14 days after treatment.
• MIC of ceftriaxone of isolates [From enrollment to 14 days after treatment]: MIC of ceftriaxone of isolates at screening and test-of-cure (TOC) visits.
• NG-MAST [From enrollment to 14 days after treatment]: NG-MAST at screening and TOC visits.
• Gene mutations associated with drug resistance for extended-spectrum cephalosporins [From enrollment to 14 days after treatment]: Gene mutations associated with drug resistance for extended-spectrum cephalosporins at screening and TOC visits.

Sex: Male, ages: 18 Years to any

Inclusion Criteria:

* 18 years or older man, and
* having oropharyngeal, anorectal or urogenital N. gonorrhoeae infection confirmed by culture or a positive NAAT

Exclusion Criteria:

* Suspicion of a complicated N. gonorrhoeae infection. Complicated N. gonorrhoeae infection is defined as the presence of epididymitis, arthritis, bacteremia, conjunctivitis, or disseminated gonococcal infection.
* Use of systemic cephalosporins, doxycycline, or azithromycin at the screening visit or within 30 days prior to the enrollment visit is prohibited. Participants who require immediate antibiotic treatment at the screening visit, based on clinician judgment or shared decision-making with the participant, without awaiting PCR or culture confirmation, will be excluded from the study. Use of doxycycline for post-exposure prophylaxis (Doxy-PEP) is permitted.
* A NAAT test positive for C. trachomatis or M. genitalium at the screening visit.
* A history of allergy or intolerance to ceftriaxone, penicillins, or lidocaine, in alignment with the contraindications listed in the Sintrix (ceftriaxone) injection package insert. Allergy or intolerance is defined as the occurrence of adverse symptoms following antibiotic administration, including but not limited to skin rash, pruritus, dyspnea, angioedema, anaphylaxis, dizziness, nausea, vomiting, headache, or diarrhea. Laboratory abnormalities include cytopenias, eosinophilia, and elevated levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, or creatinine. Penicillins include natural penicillins (e.g., penicillin G), aminopenicillins (e.g., amoxicillin, ampicillin), penicillinase-resistant penicillins (e.g., oxacillin, dicloxacillin), extended-spectrum penicillins (e.g., piperacillin), and other agents classified within the penicillin class.

• Study Protocol and Statistical Analysis Plan (PDF, 2025-09-30)