Clinical trial NCT00322465
Conditions: Urethritis
Keywords: non-gonococcal urethritis, doxycycline, azithromycin, sexually transmitted, tinidazole
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2006-11-01; Completion date: 2009-04-01
Enrollment: 305 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will look at the safety, effectiveness, and tolerability of combination medications for the initial treatment of non-gonococcal urethritis (NGU). NGU is inflammation of the tube that carries urine from the bladder. NGU is caused by bacteria that may be passed from person to person during sex. This study will compare the 2 currently recommended NGU treatments, doxycycline and azithromycin, taken with tinidazole (another medication to treat certain sexually transmitted infections). Tinidazole used with doxycycline or azithromycin may cure NGU better than when doxycycline or azithromycin is used alone. Study participants will be 300 men ages 16-45 years with NGU attending sexually transmitted disease clinics in Birmingham, AL; New Orleans, LA; Durham, NC; and Baltimore, MD. Study participation will last 7 weeks and involve 3 visits. At each visit, participants will provide a urine sample, have 2 urethral swabs, and have their urethra checked for discharge indicating infection.

Detailed description:
This study represents a clinical evaluation of the use of combination therapy for the initial treatment of non-gonococcal urethritis (NGU). This study will provide more current data on the comparison of cure rates between the 2 currently recommended therapies for NGU, doxycycline and azithromycin. Emerging clinical data has suggested that the latter may have become more efficacious for NGU as it is more effective in eradicating Mycoplasma (M.) genitalium from the genital tract than the former. Only in vitro data, limited as it is, suggests that doxycycline should be active against M. genitalium. The researchers hypothesize that cure rates for NGU will be significantly improved for both doxycycline and azithromycin using combination therapy with tinidazole. Important safety and tolerability data will be collected with regards to the use of combination therapy. Additionally, the study will provide data on the prevalence of the targeted pathogens in 4 geographic areas and on characteristics of men with NGU that may help to target populations who would benefit the most from combination therapy. The researchers hypothesize that currently recommended initial therapies for NGU are inadequate in at least certain populations due to lack of coverage for Trichomonas (T.) vaginalis. The researchers further hypothesize that between the 2 currently recommended regimens, azithromycin will result in a greater number of cures than doxycycline due to its greater efficacy in M. genitalium infected men. The primary study objectives are to: compare the clinical cure rates of doxycycline versus doxycycline with tinidazole; and azithromycin versus azithromycin with tinidazole for the treatment of NGU; and to evaluate the safety and tolerability of doxycycline/tinidazole and azithromycin/tinidazole in the treatment of NGU. Secondary study objectives are to: evaluate microbiological cure of Chlamydia (C.) trachomatis, T. vaginalis, M. genitalium in men treated with doxycycline versus doxycycline with tinidazole; and azithromycin versus azithromycin with tinidazole. Analysis will also include: (doxycycline plus doxycycline/tinidazole) versus (azithromycin plus azithromycin/tinidazole); for the clinical cure rates, analysis will also include: (doxycycline plus doxycycline/tinidazole) versus (azithromycin plus azithromycin/tinidazole); determine the prevalence of C. trachomatis, T. vaginalis, and M. genitalium in the study population of men with non-gonococcal urethritis; determine clinical, behavioral, and demographic predictors of the above organisms in men with non-gonococcal urethritis; and collect specimens for future studies to determine the role of unique and novel pathogens in the etiology of non-gonococcal urethritis. Outcome measures include clinical failure, clinical cure, microbiological cure, and unevaluable cure assessed at the first and second follow-up visits. Study participants will include 300 men ages 16-45 years with NGU attending sexually transmitted disease clinics in Birmingham, AL; New Orleans, LA; Durham, NC; and Baltimore, MD. Subjects will be randomly assigned to 1 of 4 active treatment arms: 75 subjects doxycycline; 75 subjects doxycycline plus tinidazole; 75 subjects azithromycin; and 75 subjects azithromycin plus tinidazole.

Arms: arm 1: Doxycycline 100 mg orally twice daily (2 pills/day = 200 mg/day) for 7 days plus placebo azithromycin orally single dose and placebo tinidazole. arm 2: Doxycycline 100 mg orally twice daily for 7 days plus placebo azithromycin single dose plus tinidazole 2 gm orally single dose (4 tablets at 500 mg each). arm 3: Azithromycin 1 gram (gm) orally single dose (2 tablets at 500 milligrams (mg) each) plus doxycycline placebo twice daily for 7 days plus tinidazole placebo single dose. arm 4: Azithromycin 1 gm orally single dose (2 tablets at 500 mg each) plus doxycycline placebo twice daily for 7 days plus tinidazole single dose (4 tablets at 500 mg each).
Interventions: intervention 1: Tinidazole intervention 2: Placebo intervention 3: Doxycycline intervention 4: Azithromycin
Intervention descriptions: intervention 1: 2 gm single dose (4 tablets orally at 500 mg each). intervention 2: Placebo capsule will be filled with lactose only and be identical in appearance to the capsule of Azithromycin, Tinidazole, Doxycycline. intervention 3: 100 mg orally, twice daily for 7 days. intervention 4: 1 gram (gm) (2 tablets orally at 500 milligrams (mg) each).

Protocol documents: