A Study of Doxycycline to Treat Chlamydial Infection

Study Overview
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Brief Summary
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This is a Phase 4 blinded, randomized, active-controlled, non-inferiority trial. Persons of any gender identity will be eligible. Final evaluable population will include a minimum 596 individuals: 298 persons assigned female sex at birth (AFAB) with confirmed urogenital chlamydia (CT) and 298 persons assigned male at birth (AMAB) with confirmed rectal chlamydia (CT). Approximately 664 participants will be enrolled to achieve a minimum 596 participants who contribute primary outcome data. Randomization will be stratified by study site and sex at birth: 332 persons assigned female sex at birth (AFAB) and 332 persons assigned male sex at birth (AMAB). Participants will be randomized 1:1 to a 3-day regimen of doxycycline or a 7-day regimen of doxycycline. The study blind will be maintained by providing 7 days of identical pre-filled blister packs, one with 3 days of active treatment and 4 days of placebo, and the other with 7 days of active treatment. Participants will be asked to return 28 days after randomization (at day 29), at which time they will be re-tested for chlamydia (CT) using a laboratory-based chlamydia (CT) nucleic acid amplification test (NAAT).

Detailed Description
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This is a Phase 4 blinded, randomized, active-controlled, non-inferiority trial. Persons of any gender identity will be eligible. Final evaluable population will include a minimum 596 individuals: 298 persons assigned female sex at birth (AFAB) with confirmed urogenital chlamydia (CT) and 298 persons assigned male at birth (AMAB) with confirmed rectal chlamydia (CT). Approximately 664 participants will be enrolled to achieve a minimum 596 participants who contribute primary outcome data. Randomization will be stratified by study site and sex at birth: 332 persons assigned female sex at birth (AFAB) and 332 persons assigned male sex at birth (AMAB). Participants will be randomized 1:1 to a 3-day regimen of doxycycline or a 7-day regimen of doxycycline. The study blind will be maintained by providing 7 days of identical pre-filled blister packs, one with 3 days of active treatment and 4 days of placebo, and the other with 7 days of active treatment. Participants will be asked to return 28 days after randomization (at day 29), at which time they will be re-tested for chlamydia (CT) using a laboratory-based chlamydia (CT) nucleic acid amplification test (NAAT). The primary objective is to compare the efficacy of a 3-day vs. 7-day regimen of doxycycline for treatment of urogenital chlamydia (CT) infection in persons assigned female sex at birth (AFAB) based on proportion of participants with microbiologic cure (negative nucleic acid amplification test [NAAT] of vaginal swab and no positive nucleic acid amplification test (NAAT) of vaginal swab between study treatment and Day 29) at Day 29. Also, to compare the efficacy of a 3-day vs. 7-day regimen of doxycycline for treatment of rectal chlamydia (CT) infection in persons assigned male sex at birth (AMAB) based on proportion of participants with microbiologic cure (negative nucleic acid amplification test (NAAT) of rectal swab and no positive nucleic acid amplification test (NAAT) of rectal swab between study treatment and Day 29) at Day 29. The secondary objectives are to compare the efficacy of a 3-day vs. 7-day regimen of doxycycline for treatment of rectal CT infection in persons AFAB based on microbiologic cure. Also, to compare the efficacy of a 3-day vs. 7-day regimen of doxycycline for treatment of urethral CT infection in persons AMAB based on microbiologic cure. In addition, compare the efficacy of a 3-day vs. 7-day regimen of doxycycline for treatment of total CT infection (any anatomic site) in persons AFAB and AMAB based on microbiologic cure. Lastly, to compare the efficacy of a 3-day vs. 7-day regimen of doxycycline for treatment of rectal CT infection in persons AMAB based on microbiologic cure, stratified by lymphogranuloma venereum (LGV) status.

Official Title
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A Phase 4 Study of a 3-Day vs. 7-Day Regimen of Doxycycline for the Treatment of Chlamydial Infection

Conditions
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Chlamydial Infection

Intervention / Treatment
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* Drug: Doxycycline
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has untreated urogenital chlamydia (CT) (in persons assigned female sex at birth (AFAB)) or rectal CT (in persons assigned male sex at birth (AMAB)), diagnosed with a positive nucleic acid amplification test (NAAT) result or point-of care test * result within 14 days *Point-of-care test may or may not be FDA-cleared for CLIA waiver for diagnosis depending upon anatomic site of infection. Must be age >/=16 years (where the IRB permits individuals aged 16-17 years old to consent to research); otherwise age >/= 18 years Willing and able to understand and provide written informed consent before initiation of any study procedures Willing to complete a 7-day study drug regimen Willing to abstain from condomless anal or vaginal sex during the trial Willing and able to adhere to planned study procedures for all study visits Has valid contact information Exclusion Criteria: For persons assigned female sex at birth (AFAB): lower abdominal or pelvic pain or other signs or symptoms consistent with a clinical diagnosis of pelvic inflammatory disease (PID) Per the CDC's 2021 STD Treatment Guidelines or WHO Guidelines for the management of symptomatic STIs Signs and symptoms that, in the judgement of a qualified clinician, warrant a prolonged course of treatment with doxycycline For example, 21 days of doxycycline for presumed lymphogranuloma venereum infection. Received antimicrobial therapy active against C. trachomatis within 21 days prior to positive chlamydia (CT) test result, or between the positive chlamydia (CT) test result and study enrollment Use of the following antibiotics is exclusionary: doxycycline and related tetra- or glycylcyclines, macrolides (including azithromycin), fluoroquinolones, rifampin, quinupristin-dalfopristin, and linezolid. Note: Amoxicillin, penicillin, ceftriaxone, and other beta-lactam antibiotics are not considered exclusionary for this study. Planning to take antimicrobial therapy active against chlamydia (CT) during the study period (e.g. doxycycline post-exposure prophylaxis, treatment for Mycoplasma genitalium infection, acne, or any other non-STI medical condition). Currently enrolled in or plan to enroll in another study using antimicrobial therapy active against C. trachomatis during the study period Pregnant or lactating, or plan to become pregnant within the study period Known moderate to severe allergy to tetracyclines, excluding tetracycline-induced photosensitivity. Plan to move or travel to another location that would preclude study follow-up appointments in clinic in the next 30 days 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) Previous enrollment in this trial Any condition that, in the judgment of the investigator, precludes participation because it could affect participant safety or determination of study endpoints. Of note, the following factors will NOT exclude participants from the study: Concomitant untreated gonorrhea (rectal, pharyngeal, or urethral) or known exposure to gonorrhea in the time between CT testing and study enrollment. Gonococcus (GC) infection identified during the course of pre-screening or screening will be treated with a single dose of ceftriaxone 500mg IM without concomitant azithromycin treatment. Clinical diagnosis of concomitant untreated primary or secondary syphilis or known exposure to syphilis Urethritis among persons AMAB Contraception status Diagnosis of HIV

Ages Eligible for Study
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Minimum Age: 16 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>100 mg of doxycycline orally administered twice daily for 3 days and 4 days of placebo to assigned female at birth (AFAB) participants >/= 16 years old with confirmed urogenital Chlamydia trachomatis (CT). N=166. | Drug: Doxycycline<br>* Doxycycline is a synthetic tetracycline derivative with similar antimicrobial activity.<br>Other: Placebo<br>* Placebo<br>|
| Active Comparator: Arm 2<br>100 mg of doxycycline orally administered twice daily for 7 days to assigned female at birth (AFAB) participants >/= 16 years old with confirmed urogenital Chlamydia trachomatis (CT). N=166. | Drug: Doxycycline<br>* Doxycycline is a synthetic tetracycline derivative with similar antimicrobial activity.<br>|
| Experimental: Arm 3<br>100 mg of doxycycline orally administered twice daily for 3 and 4 days of placebo days to assigned male at birth (AMAB) participants >/= 16 years old with confirmed rectal Chlamydia trachomatis (CT). N=166. | Drug: Doxycycline<br>* Doxycycline is a synthetic tetracycline derivative with similar antimicrobial activity.<br>Other: Placebo<br>* Placebo<br>|
| Active Comparator: Arm 4<br>100 mg of doxycycline orally administered twice daily for 7 days to assigned male at birth (AMAB) participants >/= 16 years old with confirmed rectal Chlamydia trachomatis (CT). N=166. | Drug: Doxycycline<br>* Doxycycline is a synthetic tetracycline derivative with similar antimicrobial activity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of assigned female at birth (AFAB) participants with microbiologic cure as detected via vaginal swab | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day1 through Day 29 | 
| Proportion of assigned male at birth (AMAB) participants with microbiologic cure as detected via rectal swab | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29 | Day 1 through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of assigned female at birth (AFAB) participants with microbiologic cure as detected via rectal swab | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day 1 through Day 29 | 
| Proportion of assigned female at birth (AFAB) participants with microbiologic cure at all anatomic sites that were positive at baseline | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day1 through Day 29 | 
| Proportion of assigned male at birth (AMAB) participants with microbiologic cure as detected via urine | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day 1 through Day 29 | 
| Proportion of assigned male at birth (AMAB) participants with microbiologic cure at all anatomic sites that were positive at baseline | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day 1 through Day 29 | 
| Proportion of lymphogranuloma venereum (LGV)-negative assigned male at birth (AMAB) participants with microbiologic cure as detected via rectal swab. | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day 1 through Day 29 | 
| Proportion of lymphogranuloma venereum (LGV)-positive assigned male at birth (AMAB) participants with microbiologic cure as detected via rectal swab. | A participant with microbiologic cure is defined as having a negative Chlamydia trachomatis (CT) Nucleic Acid Amplification Test (NAAT) at Day 29 and no positive CT NAATs between study treatment and Day 29. | Day 1 through Day 29 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chlamydia, Doxycycline, Infection, intervention, Phase 4