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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
305
2 gm single dose (4 tablets orally at 500 mg each).
Placebo capsule will be filled with lactose only and be identical in appearance to the capsule of Azithromycin, Tinidazole, Doxycycline.
100 mg orally, twice daily for 7 days.
1 gram (gm) (2 tablets orally at 500 milligrams (mg) each).
University of Alabama Hospital - Infectious Diseases
Birmingham, Alabama, United States
Delgado Personal Health Center
New Orleans, Louisiana, United States
Johns Hopkins Hospital - Emergency Medicine
Baltimore, Maryland, United States
University of North Carolina School of Medicine - Center for Infectious Diseases
Chapel Hill, North Carolina, United States
Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea
At all study visits, unsolicited adverse events were recorded. Nausea, Vomiting, Abdominal pain, and Diarrhea were recorded using National Cancer Institute Common Toxicity Criteria (Version 3.0).
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting
At all study visits, unsolicited adverse events were recorded. Nausea, Vomiting, Abdominal pain, and Diarrhea were recorded using National Cancer Institute Common Toxicity Criteria (Version 3.0).
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset
At all study visits, unsolicited adverse events were recorded.
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain
At all study visits, unsolicited adverse events were recorded. Nausea, Vomiting, Abdominal pain, and Diarrhea were recorded using National Cancer Institute Common Toxicity Criteria (Version 3.0).
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea
At all study visits, unsolicited adverse events were recorded. Nausea, Vomiting, Abdominal pain, and Diarrhea were recorded using National Cancer Institute Common Toxicity Criteria (Version 3.0).
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
Clinical Cure of NGU: Did not meet criteria for clinical failure at last evaluable follow-up visit. Clinical Failure at first follow-up: \[Persistent symptoms AND \>= 5 polymorphonuclear leukocytes (PMNs) per 3-5 oil immersion fields (regardless of urethral discharge)\] OR Persistent urethral discharge on exam (regardless of symptoms or number of PMNs). Clinical Failure at second follow-up: \>= 5 PMNs per 3-5 oil immersion fields (regardless of symptoms or presence of urethral discharge) OR Persistent urethral discharge on exam (regardless of symptoms or number of PMNs)
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Percentage of Participants Achieving Clinical Cure of NGU With (Doxycycline Plus Doxycycline/Tinidazole) Versus (Azithromycin Plus Azithromycin/Tinidazole)
Clinical Cure of NGU: Did not meet criteria for clinical failure at last evaluable follow-up visit. Clinical Failure at first follow-up: \[Persistent symptoms AND \>= 5 PMNs per 3-5 oil immersion fields (regardless of urethral discharge)\] OR Persistent urethral discharge on exam (regardless of symptoms or number of PMNs). Clinical Failure at second follow-up: \>= 5 PMNs per 3-5 oil immersion fields (regardless of symptoms or presence of urethral discharge) OR Persistent urethral discharge on exam (regardless of symptoms or number of PMNs)
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
Microbiological cure of Chlamydia trachomatis refers to the percentage of men with NGU who were negative for Chlamydia trachomatis at the last available result and had been positive for Chlamydia trachomatis at baseline.
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
Microbiological cure of Trichomonas vaginalis refers to the percentage of men with NGU who were negative for Trichomonas vaginalis (swab and urine specimens) at the last available result and had been positive for Trichomonas vaginalis at baseline (swab or urine specimen).
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole
Microbiological Cure of Mycoplasma Genitalium refers to the percentage of men with NGU who were negative for Mycoplasma Genitalium at the last available result and had been positive for Mycoplasma Genitalium at baseline.
Time frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)
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Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis
Percentage of men with non-gonococcal urethritis that had a positive result for Chlamydia trachomatis at baseline (enrollment)
Time frame: Baseline (enrollment visit)
Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis
Percentage of men with non-gonococcal urethritis that had a positive result for Trichomonas vaginalis from a urethral swab or urine specimen at baseline (enrollment)
Time frame: Baseline (enrollment visit)
Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis
Percentage of men with non-gonococcal urethritis that had a positive result for Mycoplasma genitalium at baseline (enrollment)
Time frame: Baseline (enrollment)
Clinical, Behavioral, and Demographic Predictors of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis
Clinical, behavioral, and demographic variables considered were discharge amount and appearance; condom use last sex; new recent partner; number of partners and new partners in last 30 days as well as last 3 months; number of times vaginal sex, oral sex, or anal sex in past 30 days; always/almost always used condom in last 3 months.
Time frame: Baseline (enrollment visit)
Clinical, Behavioral, and Demographic Predictors of Trichomonas Vaginalis in Men With Non-gonococcal Urethritis
Trichomonas vaginalis was determined from urethral swab or urine specimen. Clinical, behavioral, and demographic predictors considered included discharge amount and appearance; condom use last sex; new recent partner; number of partners and new partners in last 30 days and last 3 months; number of times vaginal sex, oral sex, or anal sex in last 30 days; always/almost always used condom in last 3 months.
Time frame: Baseline (enrollment visit)
Clinical, Behavioral, and Demographic Predictors of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis
Logistic multiple regression with independent variable selection based on single variable models with p\<0.10. Participants positive at enrollment for Mycoplasma genitalium from urine specimen. Potential variables: discharge amount and appearance; condom use last sex; new recent partner, number of partners and new partners in last 30 days and last 3 months; number of times vaginal sex, oral sex, or anal sex in last 30 days; always/almost always used condom last 3 months.
Time frame: Baseline (enrollment visit)
Specimens for Future Studies to Determine the Role of Unique and Novel Pathogens in the Etiology of Non-gonococcal Urethritis
Urethral swabs and urine specimens collected at each study visit for future studies to determine the role of unique and novel pathogens in the etiology of non-gonococcal urethritis
Time frame: Baseline (enrollment); First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)