Mycoplasma Genitalium Antibiotic Susceptibility and Treatment (MEGA)

NCT00358462 | Completed Phase 3 Results DMC

• 4 other identifiers: 2699505-0143 (protocol number)U19AI031448R01AI072728
• Study Type: interventional
• Target: 606
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Urethritis

Keywords

NGU, M genitalium, Ureaplasma, azithromycin, doxycycline

Outcome Measures

Primary Outcomes (2)

• mITT Analysis of Eradication of M. Genitalium at First Follow-up Study Visit

  Microbiologic cure of M. genitalium at first follow-up visit (defined as a negative in-house PCR test performed on urine)

  approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)

• mITT Analysis of Eradication of U. Urealyticum at First Follow-up Visit

  Microbiologic cure, defined as negative PCR for U. urealyticum (if cultured), or negative culture at first follow-up visit

  3 weeks (allowable window 2-5)

Secondary Outcomes (6)

• Clinical Cure Among Case Subjects Who Were Positive for M. Genitalium at the Initial Study Visit

  approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)

• Clinical Cure Among Case Subjects Who Were Positive for Ureaplasmas at the Initial Study Visit

  approximately 3 weeks after initial study visit (allowable window is 2-5 weeks after initial study visit)

• Minimum Inhibitory Concentrations (MIC) of M. Genitalium for Azithromycin

  baseline

• Minimum Inhibitory Concentrations (MIC) of M. Genitalium for Doxycycline

  baseline

• Minimum Inhibitory Concentrations (MIC) of U. Ureaplasma Biovar 2

  baseline

Study Arms (2)

Active azithromycin+placebo doxycycline

ACTIVE COMPARATOR

Active azithromycin (1g) and placebo doxycycline

Drug: Azithromycin

Active doxycycline+placebo azithromycin

ACTIVE COMPARATOR

Active doxycycline and placebo azithromycin

Drug: Doxycycline

Interventions

Azithromycin DRUG

two 500mg tablets or four 250mg tablets administered as a single dose

Also known as: Zithromax, Zmax

Active azithromycin+placebo doxycycline

Doxycycline DRUG

one 100mg capsule administered twice daily for seven days

Also known as: Doryx, Doxychel, Monodox, Oracea, Periostat, Vibra-Tabs, Vibramycin

Active doxycycline+placebo azithromycin

Eligibility Criteria

• Age: 16 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Public Health -- Seattle & King County Sexually Transmitted Diseases Clinic located at Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Related Publications (3)

• Khosropour CM, Manhart LE, Gillespie CW, Lowens MS, Golden MR, Jensen NL, Kenny GE, Totten PA. Efficacy of standard therapies against Ureaplasma species and persistence among men with non-gonococcal urethritis enrolled in a randomised controlled trial. Sex Transm Infect. 2015 Aug;91(5):308-13. doi: 10.1136/sextrans-2014-051859. Epub 2015 Jan 23.

  PMID: 25616607 DERIVED

• Khosropour CM, Manhart LE, Colombara DV, Gillespie CW, Lowens MS, Totten PA, Golden MR, Simoni J. Suboptimal adherence to doxycycline and treatment outcomes among men with non-gonococcal urethritis: a prospective cohort study. Sex Transm Infect. 2014 Feb;90(1):3-7. doi: 10.1136/sextrans-2013-051174. Epub 2013 Oct 8.

  PMID: 24106340 DERIVED

• Manhart LE, Gillespie CW, Lowens MS, Khosropour CM, Colombara DV, Golden MR, Hakhu NR, Thomas KK, Hughes JP, Jensen NL, Totten PA. Standard treatment regimens for nongonococcal urethritis have similar but declining cure rates: a randomized controlled trial. Clin Infect Dis. 2013 Apr;56(7):934-42. doi: 10.1093/cid/cis1022. Epub 2012 Dec 7.

  PMID: 23223595 DERIVED

MeSH Terms

Conditions

Urethritis

Interventions

Azithromycin; Doxycycline

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Lisa E. Manhart, PhD - PI
• Organization: University of Washington

lmanhart@uw.edu

206-744-3646

Study Officials

• Lisa E Manhart, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: July 27, 2006
• First Posted: July 31, 2006
• Study Start: January 1, 2007
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: August 15, 2018
• Results First Posted: March 8, 2013

Record last verified: 2018-07

Locations

US (1)