Efficacy of Combination Therapies for Gonorrhea Treatment
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Randomized Clinical Trial Evaluating the Efficacy of Gentamicin/Azithromycin and Gemifloxacin/Azithromycin Combination Therapies as an Alternative Regimen for Uncomplicated Urogenital Gonorrhea|
- Number of enrollees negative by culture at cervix/urethra, regardless of history of re-exposure, divided by the number of positive gonococcal cultures at cervix/urethra at enrollment and who return within 10-17 days (microbiological cure). [ Time Frame: 10-17 days after treatment. ] [ Designated as safety issue: No ]
- Eradication of rectal or pharyngeal infection: percentage of enrollees negative by culture at Visit 2. [ Time Frame: 10-17 days after treatment. ] [ Designated as safety issue: No ]
- Clinical and antimicrobial susceptibility profile of treatment failures. [ Time Frame: Isolates obtained at a follow-up study visit after drug administration (Day 10-17 or Day 18-30). Data obtained on all treatment failures. ] [ Designated as safety issue: No ]
- Resolution of symptoms and signs (clinical cure) assessed by the proportion of patients whose gonorrhea-related symptoms present at enrollment have resolved. [ Time Frame: 10-17 days after treatment. ] [ Designated as safety issue: No ]
- Antimicrobial susceptibility profile of enrollment isolates. [ Time Frame: Isolates obtained at enrollment (Day 0). ] [ Designated as safety issue: No ]
- Safety and tolerability of each regimen: percent of treated patients experiencing mild, moderate, severe, or life-threatening adverse events (AEs) either temporarily associated or not associated with study product. [ Time Frame: Day 0 through Day 17 and until Day 30 ] [ Designated as safety issue: Yes ]
|Study Start Date:||June 2010|
|Study Completion Date:||May 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Regimen B: gemifloxacin plus azithromycin
Gemifloxacin 320 mg by mouth one time plus azithromycin 2 gm by mouth one time.
One 320 mg tablet administered orally.Drug: Azithromycin
Four 500 mg tablets will be administered orally to equal a 2 gm dose.
Experimental: Regimen A: gentamicin plus azithromycin
Gentamicin 240 mg intramuscular (IM) one time for patients greater than 45 kg or 5 mg/kg IM one time for patients less than or equal to 45 kg plus azithromycin 2 gm by mouth one time.
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.Drug: Azithromycin
Four 500 mg tablets will be administered orally to equal a 2 gm dose.
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
|United States, Alabama|
|University of Alabama Hospital - Infectious Diseases|
|Birmingham, Alabama, United States, 35249-0001|
|United States, California|
|Los Angeles County Department of Public Health - Sexually Transmitted Disease Program|
|Los Angeles, California, United States, 90007-2608|
|San Francisco Department of Public Health - San Francisco City Clinic|
|San Francisco, California, United States, 94103-4030|
|United States, Maryland|
|Johns Hopkins Bayview Medical Center - Infectious Diseases|
|Baltimore, Maryland, United States, 21224-2735|
|United States, Pennsylvania|
|Magee Women's Hospital of UPMC - Reproductive Infectious Disease Research|
|Pittsburgh, Pennsylvania, United States, 15213-3108|