Official Title: “Randomized Clinical Trial Evaluating Treatment Failure Following Recommended Therapy (Azithromycin Versus Doxycycline) for Genital Chlamydial Infection in Females in Youth Correctional Facilities”

Chlamydia is a common infection among youth and can be given from one person to another during sex. Many people who have Chlamydia have no signs of infection at all, but can pass the infection to anyone they have sex with. If not treated, Chlamydia can lead to serious health problems. This study will look at how well medicines given for Chlamydia infection work. Participants will include 380 Chlamydia-positive, non-pregnant females, ages 12-21, living in long-term, female-only, youth correctional facilities. Participants will be assigned to receive either doxycycline (2 times per day, by mouth, for 7 days) or azithromycin (1 single dose by mouth). Study procedures will include collection of at least 3 urine samples to test for Chlamydia. Study visits will occur during initial enrollment in the study, day 28 after starting treatment, and day 67. Participants will be involved in study related procedures for up to 67 days.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2011

Genital Chlamydia is a public health concern. The World Health Organization (WHO) estimates that 90 million of all new cases of sexually transmitted diseases (STDs) per year are caused by Chlamydia trachomatis. In the United States alone, approximately 3 million new cases of Chlamydia are reported yearly, and the costs associated with their management and complications exceed $2 billion. Unfortunately, at least 75% of females with Chlamydia are asymptomatic, and unless the infection is detected through Chlamydia testing (screening), their infection may be transmitted to others or lead to complications. The Centers of Disease Control and Prevention (CDC) recommends either azithromycin 1 gram (gm) by mouth (PO) once or doxycycline 100 milligrams (mg) PO twice daily (BID) for 7 days as co-equal therapies for uncomplicated Chlamydia. This phase III study is designed primarily to determine the frequency of Chlamydia treatment failure following either azithromycin or doxycycline regimens, and to assess if the efficacy of the azithromycin regimen is inferior to that of the doxycycline regimen. A secondary aim will be to determine demographic predictors of Chlamydia treatment failure following azithromycin or doxycycline treatment, and to explore clinical parameters, which distinguish those with persistent infection. The study design of this Phase III trial will address major limitations of prior Chlamydia efficacy studies and the findings will reveal both the true efficacy of azithromycin and doxycycline in uncomplicated Chlamydia in female adolescents and the factors that predict treatment failure. This study is designed primarily to determine the frequency of Chlamydia treatment failure following either azithromycin or doxycycline regimens and to evaluate whether the efficacy of the azithromycin regimen is inferior to the doxycycline regimen.

Both drugs are Food and Drug Administration (FDA) approved for use in the U.S. Females age 12-21 years in good health (based on vital signs and provider's clinical evaluation documented in medical records) who are residing in long-term female-segregated (not co-ed) youth correctional facilities (YCFs) (usual stay >3 weeks) and who are identified as Chlamydia-infected would comprise the study population. Only individuals who have a positive Chlamydia screening test are enrolled, and those with negative screening tests are excluded.

Consenting Chlamydia-positive subjects at the enrollment visit [study visit #1) will be enrolled, asked to provide demographic data, to provide a first-void urine sample (not a mid-stream specimen) for repeat Chlamydia testing with Gen-Probe (GP) AC2 (for verification of Chlamydia), and then randomized to 1 of 2 treatment arms (190 subjects per arm):

doxycycline 100 mg PO BID for 7 days or azithromycin 1 gm PO single dose. Both therapies are given as directly observed, and side effects are evaluated at the first follow-up visit (day 28 after study drug initiation). If a subject who's GP AC2 from the enrollment treatment visit returns negative for C. trachomatis, they will be categorized as unevaluable and will be removed from the study, then the site investigator will determine whether the subject will complete this treatment or will receive other therapy. Subjects whose GP AC2 at the enrollment treatment visit is positive for C. trachomatis will then be asked to provide a first-void urine sample for repeat Chlamydia testing with GP AC2 at 28- and 67-days after study drug initiation (corresponding to the first follow-up visit [study visit #2] and second follow-up visit [study visit #3], respectively).

Intervention(s) in this Clinical Trial

• Drug: Azithromycin
  • FDA approved, a 1 gm single dose, two 500 mg tablets.
• Drug: Doxycycline
  • FDA approved, a 100 mg capsule twice a day for 7 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Azithromycin
  • Azithromycin 1 gm oral single dose.
• Experimental: Doxycycline
  • Doxycycline 100 mg oral twice a day (BID) for 7 days.

Primary Measures

• Microbiological cure; microbiological failure; unevaluable and indeterminate outcome.
  • Time Frame: Study visit # 2 (Day 28 after therapy started) and study visit # 3 (Day 67 after therapy started).
    Safety Issue?: No

Secondary Measures

• Evaluate whether demographical characteristics and clinical parameters predict treatment outcome.
  • Time Frame: Baseline, study visit #2 (Day 28 after therapy is started) and study visit #3 (Day 67 after therapy is started).
    Safety Issue?: No

Inclusion Criteria:

• Female between the ages of 12 and 21 years
• Residing in a long-term female-segregated (no co-ed) youth correctional facility (YCF)
• Diagnosed with genital Chlamydia as determined by a screening C. trachomatis nucleic acid amplification test (NAAT)
• Anticipated length of stay at the YCF at the time of enrollment is > 3 weeks
• Willingness to provide written consent
• Willingness to comply with study procedures

Exclusion Criteria:

• Diagnosed with gonorrhea as determined by a screening Neisseria gonorrhoeae nucleic acid amplification test (NAAT)
• Clinical diagnosis of pelvic inflammatory disease (PID) based on review of medical records
• Known allergy to tetracyclines or macrolides
• Currently pregnant or breastfeeding
• History of photosensitivity related to doxycycline use
• Having received antimicrobial therapy with activity against C. trachomatis within 21 days of the positive Chlamydia screening NAAT or in the interval between the positive screening NAAT and study enrollment
• Any concomitant infection, which requires antimicrobial therapy with activity against
• C. trachomatis
• Previously enrolled in this study
• Unable to swallow pills
• Other exclusion criteria, per clinician judgment, that prohibits subject from enrolling in study
• Of note, current use of oral contraceptive agents (OCPs) is not an

  exclusion criteria

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 12 Years

Maximum Age for this Clinical Trial: 21 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Overall Contact: William M Geisler (205) 934-4376 

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00980148

Study ID Number: 07-0012

ClinicalTrials.gov Identifier: NCT00980148

Health Authority: United States: Institutional Review Board