Treatment Failure of Chlamydial Infection in Males and Females in Youth Correctional Facilities

Study Overview
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Brief Summary
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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. The study requires 306 evaluable subjects, chlamydia-positive, males and non-pregnant females, ages 12-21, living in long-term, gender-segregated 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.

Detailed Description
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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 (C.) 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 percent 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. 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 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. The study will enroll 650 males and 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 gender-segregated (not co-ed) youth correctional facilities (YCFs) (usual stay >3 weeks) and who are identified as chlamydia-infected would comprise the study population until 306 evaluable subjects are obtained . 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 (190 153 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].

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

Conditions
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Chlamydial Infection

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Doxycycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between the ages of 12 and 21 years Residing in a long-term gender-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) or epididymitis 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 criterion

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm2<br>Doxycycline 100 mg oral twice a day (BID) for 7 days; 153 subjects | Drug: Doxycycline<br>* FDA approved, a 100 mg capsule twice a day for 7 days.<br>|
| Experimental: Arm 1<br>Azithromycin 1 gm oral single dose; 153 subjects | Drug: Azithromycin<br>* FDA approved, a 1 gm single dose, two 500 mg tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess Microbiological Failure of Recommended Azithromycin and Doxycycline Regimens in Uncomplicated Chlamydia Trachomatis Infection in a Setting Where Repeat Exposure to Chlamydia-infected Persons Can be Minimized. | The proportion of participants with testing by Gen-Probe Aptima Combo 2 that is positive for C. trachomatis and C. trachomatis OmpA (Major Outer Membrane Protein) genotyping reveals the baseline chlamydial strain and the repeat positive chlamydial strain to be the same genotype (i.e., concordant). | Study visit # 2 (Day 28 after therapy started) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographical Characteristics and Clinical Parameters to Predict Treatment Outcome. |  | Baseline and study visit #2 (Day 28 after therapy is started) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chlamydia trachomatis, Chlamydia, Doxycycline, Azithromycin