Short Course Regimen of Doxycycline for the Treatment of Chlamydial Infection
Study Details
Study Description
Brief Summary
Participants will take a 3-day course of doxycycline or a 7-day course of doxycycline to treat urogenital chlamydia infections (women) and rectal infections (men).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) in the world, with an estimated 232 million incident infections in 2019. Prior to 2021, the Centers for Disease Control and Prevention (CDC) Sexually Transmitted Infection (STI) Treatment Guidelines recommended either doxycycline (100 mg twice daily for 7 days) or azithromycin (1 gram single dose) for the treatment of both rectal and urogenital CT. The 2021 revised guidelines recommend doxycycline as the preferred treatment for CT, except for pregnant women and "persons for whom adherence with multiday dosing is a considerable concern." The 2021 World Health Organization (WHO) Guidelines for symptomatic STI treatment also recommend a seven-day regimen of doxycycline for CT treatment. The extent to which this recommendation will be translated into practice remains to be seen, since many clinicians prefer to use azithromycin due to the relative ease of a single dose treatment and possibility for directly observed therapy in some settings. Clinicians have raised concerns about incomplete patient adherence to a week-long regimen, particularly in adolescents.
One impetus for changing the CT treatment guidelines was the available evidence that doxycycline is substantially superior for treatment of rectal CT compared to azithromycin. Rectal CT is well-recognized as a common infection among cisgender men who have sex with men (MSM) and other persons assigned male at birth (AMAB) but is often overlooked among cisgender women and other persons assigned female at birth (AFAB). Increasing evidence demonstrates that rectal CT is common and may impact treatment success for concomitant urogenital infections among women. Among cisgender women, the prevalence of rectal CT among clinic patients is 8-9%, and approximately 70% of women with urogenital CT have concurrent rectal CT. However, routine screening for rectal CT is not recommended for cisgender women because the clinical implications of this infection are uncertain. Undiagnosed and inadequately treated rectal infections may lead to infections or re-infections in the urogenital tract, but there is insufficient evidence for that hypothesis to date. To the extent that women are treated with azithromycin rather than doxycycline due to adherence concerns, unrecognized and inadequately treated rectal infections may contribute to urogenital re-infection and adverse reproductive health outcomes.
The full 7-day regimen of doxycycline may not be required to cure CT infection. Clinical trials using less frequent doxycycline regimens or higher initial doses of doxycycline have demonstrated cure rates of 98%, and observational evidence suggests that partial adherence to the 7-day regimen is sufficient to achieve clinical cure.
This study will examine the non-inferiority of a 3-day regimen of doxycycline compared to the recommended 7-day regimen for the treatment of both rectal and urogenital CT. If this shorter regimen is found to be non-inferior to the standard 7-day regimen, it is anticipated that uptake of doxycycline for CT treatment will become more widespread, leading to better individual and public health outcomes compared to widespread use of azithromycin, and at a lower cost with more judicious antibiotic use than a 7-day doxycycline regimen.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 3-Day Regimen of Doxycycline Participants randomized to receive doxycycline for 3 days for treatment of chlamydial infection. |
Drug: 3-Day Regimen of Doxycycline
Participants will receive a 7-day pre-filled medication container with 3 days of doxycycline active treatment and 4 days of a placebo to match doxycycline. The active treatment is 100 milligrams (mg) of doxycycline administered orally twice per day. A placebo capsule of lactose monohydrate will be administered orally twice per day on Days 4-7.
|
| Active Comparator: 7-Day Regimen of Doxycycline Participants randomized to receive doxycycline for 7 days for treatment of chlamydial infection. |
Drug: 7-Day Regimen of Doxycycline
Participants will receive a 7-day pre-filled medication container with 7 days of doxycycline active treatment. The active treatment is 100 mg of doxycycline administered orally twice per day.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants with Microbiological Cure of Urogenital Infection in Persons Assigned Female at Birth (AFAB) [Day 29]
Microbiological cure is defined as a negative nucleic acid amplification test (NAAT) of vaginal swab at Day 29, without a positive NAAT of vaginal swab between treatment and Day 29.
- Number of Participants with Microbiological Cure of Rectal Infection in Persons Assigned Male at Birth (AMAB) [Day 29]
Microbiological cure is defined as a negative NAAT of rectal swab at Day 29, without a positive NAAT of rectal swab between treatment and Day 29.
Secondary Outcome Measures
- Number of Participants with Microbiological Cure of Rectal Infection in Persons AFAB [Day 29]
Microbiological cure is defined as a negative NAAT of rectal swab at Day 29, without a positive NAAT of rectal swab between treatment and Day 29.
- Number of Participants with Microbiological Cure of Urethral Infection in Persons AMAB [Day 29]
Microbiological cure is defined as a negative NAAT of urine at Day 29, without positive NAAT of urine between treatment and Day 29.
- Number of Participants with Microbiological Cure of total CT Infection in Persons AFAB [Day 29]
Microbiological cure is defined as a negative NAAT at all anatomic sites that were positive at baseline at Day 29, without positive NAAT at any anatomic sites between treatment and Day 29.
- Number of Participants with Microbiological Cure of total CT Infection in Persons AMAB [Day 29]
Microbiological cure is defined as a negative NAAT at all anatomic sites that were positive at baseline at Day 29, without positive NAAT at any anatomic sites between treatment and Day 29.
- Number of Participants with Microbiological Cure of Rectal Infection in Persons AMAB, Stratified by Lymphogranuloma Venereum (LGV) Status [Day 29]
Microbiological cure is defined as a negative NAAT of rectal swab at Day 29, without a positive NAAT of rectal swab between treatment and Day 29.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has untreated urogenital CT (in persons AFAB) or rectal CT (in persons AMAB), diagnosed by a positive NAAT result or point-of care test result within 14 days
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Must be age ≥16 years (where the Institutional Review Board (IRB) permits individuals aged 16-17 years old to consent to research); otherwise age > 18 years
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Willing and able to understand and provide written informed consent before initiation of any study procedures
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Willing to complete a 7-day study drug regimen
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Willing to abstain from condomless anal or vaginal sex during the trial
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Willing and able to adhere to planned study procedures for all study visits
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Has valid contact information
Exclusion Criteria:
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For persons AFAB: lower abdominal or pelvic pain or other signs or symptoms consistent with a clinical diagnosis of pelvic inflammatory disease (PID)
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Signs and symptoms that, in the judgement of a qualified clinician, warrant a prolonged course of treatment with doxycycline
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Received antimicrobial therapy active against C. trachomatis within 21 days prior to positive CT test result, or between the positive CT test result and study enrollment
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Planning to take antimicrobial therapy active against CT during the study period (e.g. doxycycline post-exposure prophylaxis, treatment for Mycoplasma genitalium infection, acne, or any other non-STI medical condition)
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Currently enrolled in or plan to enroll in another study using antimicrobial therapy active against C. trachomatis during the study period
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Pregnant or lactating, or plan to become pregnant within the study period
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Known moderate to severe allergy to tetracyclines, excluding tetracycline-induced photosensitivity
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Plan to move or travel to another location that would preclude study follow-up appointments in clinic in the next 30 days
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Use of a medication contraindicated to treatment with doxycycline within 7 days prior to enrollment or during the study period (systemic retinoids, barbiturates, carbamazepine, phenytoin, warfarin)
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Previous enrollment in this trial
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Any condition that, in the judgment of the investigator, precludes participation because it could affect participant safety or determination of study endpoints
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Emory University Hospital Midtown | Atlanta | Georgia | United States | 30308 |
| 2 | Grady Infectious Diseases Clinic (Ponce Clinic) | Atlanta | Georgia | United States | 30308 |
| 3 | University of Rochester | Rochester | New York | United States | 14627 |
| 4 | University of Washington Harborview Medical Center | Seattle | Washington | United States | 98104 |
| 5 | Ganjoni Clinic | Mombasa | Kenya | ||
| 6 | Partners in Health, Research and Development | Thika | Kenya |
Sponsors and Collaborators
- Emory University
- Infectious Diseases Clinical Research Consortium
Investigators
- Principal Investigator: Julia Dombrowski, MD, MPH, University of Washington
- Principal Investigator: Christine Khosropour, PhD, MPH, University of Washington
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EUCC-DMID-22-0019