Urethritis
Conditions
Keywords
non-gonococcal urethritis, doxycycline, azithromycin, sexually transmitted, tinidazole
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.
Interventions
DRUGTinidazole
2 gm single dose (4 tablets orally at 500 mg each).
OTHERPlacebo
Placebo capsule will be filled with lactose only and be identical in appearance to the capsule of Azithromycin, Tinidazole, Doxycycline.
DRUGDoxycycline
100 mg orally, twice daily for 7 days.
DRUGAzithromycin
1 gram (gm) (2 tablets orally at 500 milligrams (mg) each).
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
16 Years to 45 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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). |
| Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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). |
| Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | At all study visits, unsolicited adverse events were recorded. |
| Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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). |
| Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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). |
| Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | Baseline (enrollment) | Percentage of men with non-gonococcal urethritis that had a positive result for Mycoplasma genitalium at baseline (enrollment) |
| Clinical, Behavioral, and Demographic Predictors of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | Baseline (enrollment visit) | 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. |
| Percentage of Participants Achieving Clinical Cure of NGU With (Doxycycline Plus Doxycycline/Tinidazole) Versus (Azithromycin Plus Azithromycin/Tinidazole) | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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) |
| Clinical, Behavioral, and Demographic Predictors of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | Baseline (enrollment visit) | 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. |
| Specimens for Future Studies to Determine the Role of Unique and Novel Pathogens in the Etiology of Non-gonococcal Urethritis | Baseline (enrollment); First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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 |
| Clinical, Behavioral, and Demographic Predictors of Trichomonas Vaginalis in Men With Non-gonococcal Urethritis | Baseline (enrollment visit) | 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. |
| Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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. |
| Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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). |
| Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | First follow-up visit (Day 15-19), second follow-up visit (Day 35-45) | 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. |
| Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | Baseline (enrollment visit) | Percentage of men with non-gonococcal urethritis that had a positive result for Chlamydia trachomatis at baseline (enrollment) |
| Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis | Baseline (enrollment visit) | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Doxycycline Doxycycline 100 mg by mouth twice a day (2 pills/day = 200 mg/day) for 7 days plus placebo azithromycin by mouth single dose and placebo tinidazole. | 76 |
| Doxycycline + Tinidazole Doxycycline 100 mg by mouth twice a day for 7 days plus placebo azithromycin single dose plus tinidazole 2 gm by mouth single dose (4 tablets at 500 mg each). | 73 |
| Azithromycin Azithromycin 1 gm by mouth single dose (2 tablets at 500 mg each) plus doxycycline placebo twice a day for 7 days plus tinidazole placebo single dose. | 77 |
| Azithromycin + Tinidazole Azithromycin 1 gm by mouth single dose (2 tablets at 500 mg each) plus doxycycline placebo twice a day for 7 days plus tinidazole single dose (4 tablets at 500 mg each). | 79 |
| Total | 305 |
Baseline characteristics
| Characteristic | Total | Doxycycline | Doxycycline + Tinidazole | Azithromycin | Azithromycin + Tinidazole |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 1 Participants | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 298 Participants | 75 Participants | 72 Participants | 75 Participants | 76 Participants |
| Age, Continuous | 26.8 years STANDARD_DEVIATION 6.9 | 27.3 years STANDARD_DEVIATION 7 | 27.8 years STANDARD_DEVIATION 6.8 | 26.4 years STANDARD_DEVIATION 6.7 | 25.7 years STANDARD_DEVIATION 7.2 |
| Region of Enrollment United States | 305 participants | 76 participants | 73 participants | 77 participants | 79 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 305 Participants | 76 Participants | 73 Participants | 77 Participants | 79 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 18 / 76 | 25 / 73 | 11 / 77 | 24 / 79 |
| serious Total, serious adverse events | 0 / 76 | 0 / 73 | 0 / 77 | 0 / 79 |
Outcome results
Primary
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)
Population: Modified intent to treat: all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 47 Percentage of participants |
| Doxycycline + Tinidazole | Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 51 Percentage of participants |
| Azithromycin | Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 39 Percentage of participants |
| Azithromycin + Tinidazole | Percentage of Participants Achieving Clinical Cure of Non-gonococcal Urethritis (NGU) With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 48 Percentage of participants |
Primary
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)
Population: Modified intent-to-treat population was comprised of all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea | 0 Participants |
| Doxycycline + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea | 3 Participants |
| Azithromycin | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea | 3 Participants |
| Azithromycin + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Diarrhea | 7 Participants |
Primary
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)
Population: Modified intent-to-treat population was comprised of all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea | 3 Participants |
| Doxycycline + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea | 4 Participants |
| Azithromycin | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea | 0 Participants |
| Azithromycin + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Nausea | 4 Participants |
Primary
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)
Population: Modified intent-to-treat population was comprised of all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain | 6 Participants |
| Doxycycline + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain | 5 Participants |
| Azithromycin | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain | 3 Participants |
| Azithromycin + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting of Abdominal Pain | 5 Participants |
Primary
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)
Population: Modified intent-to-treat population was comprised of all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset | 1 Participants |
| Doxycycline + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset | 1 Participants |
| Azithromycin | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset | 1 Participants |
| Azithromycin + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Stomach Upset | 0 Participants |
Primary
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)
Population: Modified intent-to-treat population was comprised of all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting | 4 Participants |
| Doxycycline + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting | 2 Participants |
| Azithromycin | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting | 0 Participants |
| Azithromycin + Tinidazole | Safety and Tolerability of Doxycycline/Tinidazole and Azithromycin/Tinidazole: Number of Participants Reporting Vomiting | 0 Participants |
Secondary
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)
Population: All study participants who met major eligibility criteria (per protocol) with evaluable baseline measures.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Doxycycline | Clinical, Behavioral, and Demographic Predictors of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | Negative for Chlamydia Trachomatis at Baseline | 162 Participants |
| Doxycycline | Clinical, Behavioral, and Demographic Predictors of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | Positive for Chlamydia Trachomatis at Baseline | 128 Participants |
Comparison: The null hypothesis is that the odds ratio for age (per 5 years) is 1 versus the alternative that it is greater than or less than 1. This was tested in a multivariable logistic regression model.p-value: 0.00595% CI: [0.6, 0.91]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for scant discharge (reference category is no discharge) is 1 versus the alternative that it is greater than or less than 1. This was tested in a multivariable logistic regression model.p-value: 0.7895% CI: [0.33, 2.3]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for moderate discharge amount (reference category is no discharge) is 1 versus the alternative that it is greater than or less than 1. This was tested in a multivariable logistic regression model.p-value: 0.16495% CI: [0.75, 5.33]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for large amount of discharge (reference category is no discharge) is 1 versus the alternative that it is greater than or less than 1. This was tested in a multvariable logistic regression model.p-value: 0.91995% CI: [0.23, 5.17]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for 2 or more sex partners in the last 3 months (reference category is 0-1 partners) is 1 versus the alternative that it is greater than or less than 1.p-value: 0.05195% CI: [1, 3.3]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for 1 or more new sex partners in the last 30 days (reference category is 0) is 1 versus the alternative that it is greater than or less than 1.p-value: 0.07695% CI: [0.86, 22.74]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for ever having sex with a prostitute or sex for money, drugs, or other things (reference category is no) is 1 versus the alternative that it is greater than or less than 1.p-value: 0.07595% CI: [0.13, 1.1]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for visit due to sexually transmitted disease contact (reference category is no) is 1 versus the alternative that it is greater than or less than 1.p-value: <0.00195% CI: [1.93, 7.98]Regression, Logistic
Secondary
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)
Population: All study participants who met major eligibility criteria (per protocol) with evaluable baseline results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Doxycycline | Clinical, Behavioral, and Demographic Predictors of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | Positive for Mycoplasma Genitalium at Baseline | 90 Participants |
| Doxycycline | Clinical, Behavioral, and Demographic Predictors of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | Negative for Mycoplasma Genitalium at Baseline | 202 Participants |
Comparison: The null hypothesis is that the odds ratio for age (per 5 years) is 1 versus the alternative that the odds ratio is greater than or less than 1.p-value: 0.03295% CI: [0.66, 0.98]Regression, Logistic
Secondary
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)
Population: All study participants who met major eligibility criteria (per protocol) with evaluable baseline results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Doxycycline | Clinical, Behavioral, and Demographic Predictors of Trichomonas Vaginalis in Men With Non-gonococcal Urethritis | Negative for Trichomonas Vaginalis at Baseline | 253 Participants |
| Doxycycline | Clinical, Behavioral, and Demographic Predictors of Trichomonas Vaginalis in Men With Non-gonococcal Urethritis | Positive for Trichomonas Vaginalis at Baseline | 38 Participants |
Comparison: The null hypothesis is that the odds ratio for 2 or more sex partners in the last 3 months (reference category is 0-1 partners) is 1 versus the alternative that it is greater than or less than 1. This was tested in a multivariable logistic regression model.p-value: 0.00995% CI: [0.06, 0.66]Regression, Logistic
Comparison: The null hypothesis is that the odds ratio for ever having sex with a prostitute or for money, drugs, or other things(reference category is no) is 1 versus the alternative that it is greater than or less than 1. This was tested in a multivariable logistic regression model.p-value: 0.07495% CI: [0.92, 6.22]Regression, Logistic
Secondary
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)
Population: Modified intent-to-treat population was comprised of all subjects randomized who received at least one dose of study drug therapy or placebo
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Percentage of Participants Achieving Clinical Cure of NGU With (Doxycycline Plus Doxycycline/Tinidazole) Versus (Azithromycin Plus Azithromycin/Tinidazole) | 49 Percentage of participants |
| Doxycycline + Tinidazole | Percentage of Participants Achieving Clinical Cure of NGU With (Doxycycline Plus Doxycycline/Tinidazole) Versus (Azithromycin Plus Azithromycin/Tinidazole) | 44 Percentage of participants |
Secondary
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)
Population: Participants who were positive at baseline, returned for follow-up, and had evaluable test results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 89 Percentage of participants |
| Doxycycline + Tinidazole | Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 75 Percentage of participants |
| Azithromycin | Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 66 Percentage of participants |
| Azithromycin + Tinidazole | Percentage of Participants Achieving Microbiological Cure of Chlamydia Trachomatis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 61 Percentage of participants |
Secondary
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)
Population: Participants who were positive at baseline, returned for follow-up, and had evaluable test results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 23 Percentage of participants |
| Doxycycline + Tinidazole | Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 32 Percentage of participants |
| Azithromycin | Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 52 Percentage of participants |
| Azithromycin + Tinidazole | Percentage of Participants Achieving Microbiological Cure of Mycoplasma Genitalium With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 68 Percentage of participants |
Secondary
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)
Population: Participants who were positive at baseline, returned for follow-up, and had evaluable test results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 55 Percentage of participants |
| Doxycycline + Tinidazole | Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 75 Percentage of participants |
| Azithromycin | Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 56 Percentage of participants |
| Azithromycin + Tinidazole | Percentage of Participants Achieving Microbiological Cure of Trichomonas Vaginalis With Doxycycline Versus Doxycycline With Tinidazole; and Azithromycin Versus Azithromycin With Tinidazole | 50 Percentage of participants |
Secondary
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)
Population: All study participants with evaluable baseline test results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | 50 Percentage of participants |
| Doxycycline + Tinidazole | Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | 38 Percentage of participants |
| Azithromycin | Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | 38 Percentage of participants |
| Azithromycin + Tinidazole | Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis | 46 Percentage of participants |
Secondary
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)
Population: All study participants with evaluable baseline test results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | 29 Percentage of participants |
| Doxycycline + Tinidazole | Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | 30 Percentage of participants |
| Azithromycin | Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | 32 Percentage of participants |
| Azithromycin + Tinidazole | Prevalence of Mycoplasma Genitalium in Men With Non-gonococcal Urethritis | 32 Percentage of participants |
Secondary
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)
Population: All study participants with evaluable baseline test results.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Doxycycline | Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis | 14 Percentage of participants |
| Doxycycline + Tinidazole | Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis | 16 Percentage of participants |
| Azithromycin | Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis | 12 Percentage of participants |
| Azithromycin + Tinidazole | Prevalence of Trichomonas Vaginalis (Swab or Urine Specimen) in Men With Non-gonococcal Urethritis | 10 Percentage of participants |
Secondary
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)