NGU: Doxycycline (Plus or Minus Tinidazole) Versus Azithromycin (Plus or Minus Tinidazole) - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00322465

Purpose

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.

Condition	Intervention	Phase
C Trachomatis M Genitalium T Vaginalis Urethritis Non-Gonococcal Urethritis	Drug: Azithromycin Drug: Tinidazole Drug: Doxycycline Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study
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)

Resource links provided by NLM:

Drug Information available for: Doxycycline Tinidazole Doxycycline hyclate Azithromycin Doxycycline calcium

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Evaluate the safety and tolerability of doxycycline/tinidazole and azithromycin/tinidazole in the treatment of NGU. [ Time Frame: Duration of study ] [ Designated as safety issue: Yes ]
For the treatment of NGU, compare the clinical cure rates of doxycycline versus doxycycline with tinidazole; and azithromycin versus azithromycin with tinidazole. [ Time Frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical cure rates, analysis will also include: (doxycycline plus doxycycline/tinidazole) versus (azithromycin plus azithromycin/tinidazole). [ Time Frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45). ] [ Designated as safety issue: No ]
Evaluate microbiological cure of C. trachomatis, T. vaginalis, and M. genitalium in men treated with doxycycline versus doxycycline with tinidazole; and azithromycin versus azithromycin with tinidazole. [ Time Frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45). ] [ Designated as safety issue: No ]
Prevalence of C. trachomatis, T. vaginalis, and M. genitalium in men with non-gonococcal urethritis; clinical, behavioral, and demographic predictors of C. trachomatis, T. vaginalis, and M. genitalium in men with non-gonococcal urethritis. [ Time Frame: Duration of study ] [ Designated as safety issue: No ]
Collect specimens for future studies to determine the role of unique and novel pathogens in the etiology of non-gonococcal urethritis. [ Time Frame: First follow-up visit (Day 15-19), second follow-up visit (Day 35-45). ] [ Designated as safety issue: No ]

Enrollment:	305
Study Start Date:	November 2006
Study Completion Date:	May 2009
Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Doxycycline: Experimental Doxycycline 100 mg PO BID (2 pills/day = 200 mg/day) for 7 days plus placebo azithromycin PO single dose and placebo tinidazole.	Drug: Doxycycline 100 mg PO BID for 7 days. Drug: Placebo Placebo azithromycin; placebo tinidazole; and doxycycline placebo.
Doxycycline + Tinidazole: Experimental Doxycycline 100 mg PO BID for 7 days plus placebo azithromycin single dose plus tinidazole 2 gm PO single dose (4 tablets at 500 mg each).	Drug: Tinidazole 2 gm single dose (4 tablets PO at 500 mg each). Drug: Doxycycline 100 mg PO BID for 7 days. Drug: Placebo Placebo azithromycin; placebo tinidazole; and doxycycline placebo.
Azithromycin + Tinidazole: Experimental Azithromycin 1 gm PO single dose (2 tablets at 500 mg each) plus doxycycline placebo BID for 7 days plus tinidazole placebo single dose (4 tablets at 500 mg each).	Drug: Azithromycin 1 gm (2 tablets PO at 500 mg each). Drug: Tinidazole 2 gm single dose (4 tablets PO at 500 mg each). Drug: Placebo Placebo azithromycin; placebo tinidazole; and doxycycline placebo.
Azithromycin: Experimental Azithromycin 1 gm PO single dose (2 tablets at 500 mg each) plus doxycycline placebo BID for 7 days plus tinidazole placebo single dose.	Drug: Azithromycin 1 gm (2 tablets PO at 500 mg each). Drug: Placebo Placebo azithromycin; placebo tinidazole; and doxycycline placebo.

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 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 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 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

Ages Eligible for Study:	16 Years to 45 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322465

Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, Louisiana
Louisiana State University
New Orleans, Louisiana, United States, 70112
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7030

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

More Information

No publications provided

Responsible Party:	HHS/NIAID/DMID ( Robert Johnson )
Study ID Numbers:	05-0120
Study First Received:	May 4, 2006
Last Updated:	November 5, 2009
ClinicalTrials.gov Identifier:	NCT00322465 History of Changes
Health Authority:	United States: Institutional Review Board; United States: Federal Government; United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

non-gonococcal urethritis, doxycycline, azithromycin, sexually transmitted, tinidazole

Additional relevant MeSH terms:

Anti-Infective Agents
Antiprotozoal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Bacterial Agents
Antimalarials
Antiparasitic Agents
Urologic Diseases

Azithromycin
Therapeutic Uses
Urethral Diseases
Antitrichomonal Agents
Alkylating Agents
Urethritis
Doxycycline
Tinidazole

ClinicalTrials.gov processed this record on November 09, 2009