Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA)

Official Title: “Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA): A Randomized Double-blinded Treatment Trial to Assess the Efficacy of Azithromycin and Doxycycline for Clinical and Microbiological Cure of M. Genitalium in Men With Nongonococcal Urethritis”

The purpose of this study is to find out which of 2 different antibiotics, doxycycline or azithromycin, works best against germs that may cause nongonococcal urethritis.

Study participants will include approximately 1200 men, 16 years of age or older, attending a sexually transmitted diseases clinic in Seattle, Washington with clinical signs of urethral inflammation (>=5PMNs/HPF on a Gram-stained slide prepared from urethral exudates and/or a visible urethral discharge upon examination).

Urine specimens will be collected and tested for Mycoplasma genitalium and Ureaplasmas. Each participant will receive a blinded packet of study medication. Participants will answer an enrollment questionnaire and will also receive a log to complete between visits to record information about treatment adherence, side effects, symptoms, and sexual activity. All subjects will be asked to return for evaluation 3 weeks after the initial clinic visit.

Subjects who test positive for M. genitalium and/or Ureaplasmas at the initial clinic visit will also be asked to return for a third study visit, 6 weeks following the initial clinic visit. During follow-up visits, participants will answer a follow-up questionnaire and will be re-evaluated for signs of urethritis. Those who were initially positive for M. genitalium and/or Ureaplasmas will be re-tested for these organisms.

Study participants with signs and/or symptoms of urethritis or who test positive for M.

genitalium or Ureaplasmas at the follow-up study visit will receive another blinded treatment packet containing the alternate medication. Those who require additional treatment at the 6-week visit will be asked to return for a fourth follow-up study visit at 9-10 weeks. Study participants who did not test positive for M. genitalium or Ureaplasmas at the initial clinic visit, but who continue to demonstrate signs and/or symptoms of infection at their single follow-up study visit will treated according to clinic standard of care (after the study clinician unblinds their randomly-assigned treatment regimen).

OBJECTIVES

The primary objective of this study is to determine the relative effectiveness of azithromycin and doxycycline in eradicating Mycoplasma genitalium and Ureaplasmas among men with nongonococcal urethritis (NGU).

Secondary objectives of this study are to: - determine the sensitivity of persisting organisms to azithromycin and doxycycline by performing minimum inhibitory concentration (MIC) testing - determine the relationship between persistence/recurrence of clinical signs and persistent/recurrent detection of M. genitalium and Ureaplasmas among men with NGU treated with azithromycin or doxycycline, measured by follow-up clinical exams and repeated assays performed on specimens collected at follow-up study visits

STUDY DESCRIPTION

1200 men with NGU, ages 16 and older, will be enrolled in a randomized double-blinded treatment trial. Urine samples, oral swabs, and urethral swabs will be obtained from each subject at the initial clinic visit. Urine specimens will be tested for M. genitalium and Ureaplasma. Study participants will be randomly assigned to receive one of two pre-packaged treatments: active doxycycline plus placebo azithromycin or active azithromycin plus placebo doxycycline. Subjects will complete a questionnaire, and will be given a simple standardized log in which they will be asked to keep track of adherence to the study drug, record solicited adverse events, note when symptoms disappear and/or reappear, and document sexual activity between study visits.

Subjects who test positive for M. genitalium or Ureaplasmas at the initial clinic visit will be asked to return for at least two follow-up study visits: at approximately 3 and 6 weeks following the initial clinic visit. During follow-up visits, participants will answer a follow-up questionnaire and will be re-evaluated for signs of urethritis and re-tested for M. genitalium and Ureaplasmas. Study participants with signs and/or symptoms of urethritis or who test positive for M. genitalium or Ureaplasmas at the follow-up study visits will receive a blinded treatment packet containing the alternate medication, or will be offered open-label moxifloxacin if the alternate treatment regimen was administered at the prior follow-up study visit. If additional treatment is administered at the 6-week follow-up study visit, a fourth study visit will be scheduled to occur approximately 9 or 10 weeks following the initial clinic visit.

Study participants who were negative for M. genitalium and Ureaplasma at enrollment will be asked to return for evaluation for a single follow-up study visit, approximately 3 weeks after the initial clinic visit. At this visit they will complete the follow-up questionnaire and provide specimens for future testing.

Intervention(s) in this Clinical Trial

• Drug: Azithromycin
  • two 500mg tablets or four 250mg tablets administered as a single dose
• Drug: Doxycycline
  • one 100mg capsule administered twice daily for seven days

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Active azithromycin and placebo doxycycline
• Active Comparator: 2
  • Active doxycycline and placebo azithromycin

Primary Measures

• Eradication of M. genitalium or Ureaplasmas at first follow-up study visit
  • Time Frame: approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)
    Safety Issue?: No

Secondary Measures

• Minimum inhibitory concentrations (MIC) of all cultivable strains of M. genitalium and Ureaplasmas
  • Time Frame: on-going
    Safety Issue?: No
• Clinical cure as measured by the absence of recurrent or persistent signs and/or symptoms of urethral infection among case subjects who were positive for M. genitalium or Ureaplasmas at the initial study visit
  • Time Frame: approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)
    Safety Issue?: No

Inclusion Criteria:

• Has a visible urethral discharge or greater than or equal to 5 polymorphonuclear leukocytes (PMNs) per high power field on a Gram-stained slide of a urethral swab sample
• Possesses and is willing to disclose valid contact information for follow-up
• English-speaking
• Gives informed consent
• Exhibits understanding of study procedures
• Exhibits ability to comply with study procedures for the entire length of the study

Exclusion Criteria:

• Has previously participated in this study
• Has taken antibiotics within the prior month
• Has known allergies to tetracyclines or azithromycin
• Is being treated with any of the following: warfarin, ergot derivatives, pimozide (Orap), propafenone (Rytmonorm, Rythmol), disopyramide (Norpace, Rythmodan), rifampin, digoxin, isotretinoin, or methotrexate
• Has received a kidney, heart, or lung transplant.
• Is undertaking concomitant systemic steroid therapy

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: University of Washington Other

Overall Clinical Trial Officials and Contacts

Overall Contact: Lisa E. Manhart, PhD (206) 744-3646 lmanhart@u.washington.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00358462

Study ID Number: 26995-D

ClinicalTrials.gov Identifier: NCT00358462

Health Authority: United States: Institutional Review Board