NGU: Doxycycline (Plus or Minus Tinidazole) Versus Azithromycin (Plus or Minus Tinidazole)

NCT00322465 | Completed Phase 2 Results

• 1 other identifier: 05-0120
• Study Type: interventional
• Target: 305
• Locations: 1 country
• Sites: 4

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.

Conditions

Urethritis

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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).

  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).

  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.

  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).

  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).

  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)

  First follow-up visit (Day 15-19), second follow-up visit (Day 35-45)

Secondary Outcomes (11)

• 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)

• 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)

• 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)

• 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)

• Prevalence of Chlamydia Trachomatis in Men With Non-gonococcal Urethritis

  Baseline (enrollment visit)

Study Arms (4)

Doxycycline

EXPERIMENTAL

Doxycycline 100 mg orally twice daily (2 pills/day = 200 mg/day) for 7 days plus placebo azithromycin orally single dose and placebo tinidazole.

Other: Placebo; Drug: Doxycycline

Doxycycline + Tinidazole

EXPERIMENTAL

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).

Drug: Tinidazole; Other: Placebo; Drug: Doxycycline

Azithromycin

EXPERIMENTAL

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.

Other: Placebo; Drug: Azithromycin

Azithromycin + Tinidazole

EXPERIMENTAL

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).

Drug: Tinidazole; Other: Placebo; Drug: Azithromycin

Interventions

Tinidazole DRUG

2 gm single dose (4 tablets orally at 500 mg each).

Azithromycin + Tinidazole; Doxycycline + Tinidazole

Placebo OTHER

Placebo capsule will be filled with lactose only and be identical in appearance to the capsule of Azithromycin, Tinidazole, Doxycycline.

Azithromycin; Azithromycin + Tinidazole; Doxycycline; Doxycycline + Tinidazole

Doxycycline DRUG

100 mg orally, twice daily for 7 days.

Doxycycline; Doxycycline + Tinidazole

Azithromycin DRUG

1 gram (gm) (2 tablets orally at 500 milligrams (mg) each).

Azithromycin; Azithromycin + Tinidazole

Eligibility Criteria

• Age: 16 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (4)

University of Alabama Hospital - Infectious Diseases

Birmingham, Alabama, 35249-0001, United States

Location

Delgado Personal Health Center

New Orleans, Louisiana, 70112-3503, United States

Location

Johns Hopkins Hospital - Emergency Medicine

Baltimore, Maryland, 21287-0005, United States

Location

University of North Carolina School of Medicine - Center for Infectious Diseases

Chapel Hill, North Carolina, 27599-7030, United States

Location

Related Publications (1)

• 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.

  PMID: 21288838 RESULT

MeSH Terms

Conditions

Urethritis

Interventions

Tinidazole; Doxycycline; Azithromycin

Condition Hierarchy (Ancestors)

Urethral Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nitroimidazoles; Nitro Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones

Results Point of Contact

• Title: Jane R. Schwebke, MD
• Organization: University of Alabama at Birmingham

schwebke@uab.edu

(205) 975-5665

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2006
• First Posted: May 8, 2006
• Study Start: November 1, 2006
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: March 1, 2019
• Results First Posted: August 17, 2011

Record last verified: 2011-05

Locations

US (4)