Clinical trial NCT00322465: NGU: Doxycycline (Plus or Minus Tinidazole) Versus Azithromycin (Plus or Minus Tinidazole)
Official title: Phase II Randomized, Placebo-Controlled Double-Blind 4-Arm Trial for the Treatment of Non-Gonococcal Urethritis (NGU): Doxycycline (Plus or Minus Tinidazole) Versus Azithromycin (Plus or Minus Tinidazole)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Urethritis
Keywords: non-gonococcal urethritis, doxycycline, azithromycin, sexually transmitted, tinidazole
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2006-05-08
Enrollment: 305
Sex: MALE
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Male, 16 to 45 years old.
* Symptoms of non-gonococcal urethritis (NGU), including urethral discharge and/or dysuria for less than or equal to 14 days, or urethral discharge on exam.
* Urethral smear with greater than or equal to 5 polymorphonuclear leukocytes (PMNs) per 3-5 oil immersion fields.
* Willing to abstain from sexual intercourse or use condoms during the study.
* Willingness to provide written consent.

Exclusion Criteria:

* Presence of gonorrhea at baseline visit.
* History of recurrent non-gonococcal urethritis (NGU) (3 or more episodes in the prior year) or history of recent NGU (within past 30 days).
* Signs or symptoms of epididymitis or prostatitis.
* Known allergy to or intolerance of tinidazole, tetracyclines, macrolides or metronidazole.
* History of photosensitivity related to doxycycline use.
* Received systemic antibiotics within 30 days of study enrollment.
* Unwillingness to abstain from alcohol for 24 hours after enrollment.
* Serious underlying infection, including known HIV or other primary or secondary immunosuppression.
* Concomitant infection, which requires antimicrobial therapy.
* History of mental illness, which would preclude responsible participation in the study.
* Current drug abuse that might affect ability to follow the protocol.
* Previously enrolled in this study.
* Men who have sex with men, due to different microbiology of NGU.
* Voided within the previous hour.
* Ingested alcohol within the past 8 hours.
* Subject requires concurrent lithium, anticoagulation therapy, or antabuse.

Primary outcomes:
measure: Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Secondary outcomes:
measure: Percentage of Participants Achieving Clinical Cure of NGU With (Doxycycline Plus Doxycycline/Tinidazole) Versus (Azithromycin Plus Azithromycin/Tinidazole)
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
timeFrame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
measure: Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis
timeFrame: Baseline (enrollment visit)
measure: Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis
timeFrame: Baseline (enrollment visit)
measure: Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis
timeFrame: Baseline (enrollment)
measure: Clinical, Behavioral, and Demographic Predictors of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis
timeFrame: Baseline (enrollment visit)
measure: Clinical, Behavioral, and Demographic Predictors of Trichomonas Vaginalis in Men With Non-gonococcal Urethritis
timeFrame: Baseline (enrollment visit)
measure: Clinical, Behavioral, and Demographic Predictors of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis
timeFrame: Baseline (enrollment visit)
measure: Specimens for Future Studies to Determine the Role of Unique and Novel Pathogens in the Etiology of Non-gonococcal Urethritis
timeFrame: Baseline (enrollment); First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Hospital - Infectious Diseases
state: Alabama
city: New Orleans
country: United States
facility: Delgado Personal Health Center
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital - Emergency Medicine
state: Maryland
city: Chapel Hill
country: United States
facility: University of North Carolina School of Medicine - Center for Infectious Diseases
state: North Carolina
Study officials:
References:
citation: Schwebke JR, Rompalo A, Taylor S, Sena AC, Martin DH, Lopez LM, Lensing S, Lee JY. Re-evaluating the treatment of nongonococcal urethritis: emphasizing emerging pathogens--a randomized clinical trial. Clin Infect Dis. 2011 Jan 15;52(2):163-70. doi: 10.1093/cid/ciq074.