Efficacy of Combination Therapies for Gonorrhea Treatment
Condition: Gonorrhoea
MeSH terms: Gonorrhea
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to learn how to better treat gonorrhea infections. Gonorrhea is
      a sexually transmitted disease (STD) that is usually cured with a single antibiotic. However,
      some gonorrhea is not cured with a single antibiotic. The study will look at how well
      treating gonorrhea with 2 antibiotics works. Participants will be assigned to 1 of 2
      treatment groups each receiving a combination of 2 antibiotics. Sites in the United States
      will recruit 500 male and female participants. Participants must be 15 to 60 years old, in
      good health and identified in participating sexually transmitted disease clinics as having
      uncomplicated cervical or urethral gonorrhea. Procedures include collection of current
      symptoms, medical and sexual history, sexual orientation, vital signs, height, weight,
      cervical/urethral cultures and clinical examinations. Volunteers will be involved for about
      17 days.
    

Detailed description: 
      Infection with Neisseria (N.) gonorrhoeae carries a significant public health burden in the
      United States (U.S.). Gonococcal infection can result in pelvic inflammatory disease (PID),
      ectopic pregnancy, infertility, chronic pelvic pain, and increases the risk of transmission
      and acquisition of human immunodeficiency virus (HIV). With over 350,000 cases of gonorrhea
      reported each year, gonorrhea is the second most common notifiable condition. Furthermore, it
      is estimated that case reports account for only half of the incident cases of gonorrhea in
      the U.S. each year. Given that gonorrhea is a bacterial infection which causes symptoms in
      approximately 90 percent of infected men and 50 percent of infected women, the most critical
      aspect of reducing the public health burden of gonorrhea for affected populations is
      provision of effective antimicrobial therapy. In order to identify treatment options for
      patients with suspect or confirmed cephalosporin-resistant N. gonorrhoeae infection and
      patients with severe cephalosporin hypersensitivity, this study plans to determine the
      efficacy of each of 2 combination antimicrobial regimens for the treatment of uncomplicated
      gonococcal infection. This study is a multicenter clinical trial of adult males and females
      diagnosed with urethral or cervical gonococcal infection. Subjects will be enrolled and
      randomized for treatment with either Regimen A: gentamicin 240 mg intramuscular (IM) one time
      for patients >45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus
      azithromycin 2 gm by mouth (PO) one time, or Regimen B: gemifloxacin 320 mg PO one time plus
      azithromycin 2 gm PO one time. Investigators hypothesize that Regimen A will have a clinical
      efficacy estimate that is greater than or equal to 95 percent as well as a lower, one-sided
      95 percent confidence interval (CI 95 percent) bound that is greater than or equal to 90
      percent. The identical hypothesis applies for Regimen B. It should be noted that this is not
      a comparative trial between Regimen A and B, but rather a trial to establish efficacy data
      for each of these two candidate regimens. The primary objective of this study is to determine
      the microbiological efficacy of each of two combination antimicrobial regimens for the
      treatment of uncomplicated gonococcal infection (i.e., non-systemic). Secondary objectives of
      this study are to: assess the safety and tolerability of each candidate regimen; assess the
      eradication of any rectal or pharyngeal gonococcal infection by each regimen; determine the
      antimicrobial susceptibility profile of all gonococcal strains isolated at the time of
      enrollment; determine the clinical and antimicrobial susceptibility profile of all gonococcal
      strains isolated from patients who fail treatment; and assess the efficacy of the candidate
      regimens on the resolution of symptoms and signs (clinical cure). The primary efficacy
      analysis will be based on microbiological cure rate at end of trial based on the modified
      intent-to-treat (MITT) and per protocol (PP) subsets. The number, percent, and a 95 percent
      one-sided (lower) confidence interval of microbiological cure rate successes and failures
      will be computed. Additional analyses will be conducted on the following subsets: male,
      female, men who have sex with men (MSM) status, and subjects denying anal, oral, or vaginal
      intercourse during the follow-up period. Secondary endpoints will include: separate analyses
      of: safety and tolerability of each regimen; eradication of rectal or pharyngeal infection;
      antimicrobial susceptibility profile of enrollment isolates; clinical and antimicrobial
      susceptibility profile of treatment failures; and resolution of
    

Intervention name(s): Azithromycin; Gentamicin; Gemifloxacin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Four 500 mg tablets will be administered orally to equal a 2 gm dose.; Fixed dose of 240 mg intramuscular one time for patients >45 kg and a 5 mg/kg dose for patients less than or equal to 45 kg based on their measured weight in clinic. Most patients will require 2 injections of gentamicin in separate large muscle groups.; One 320 mg tablet administered orally.
Intervention MeSH terms: Azithromycin; Gentamicins; Gemifloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: gonorrhea, gonococcal infections, Neisseria gonorrhoeae