Comparisons of Treatment Responses of Early Syphilis to Benzathine Penicillin G With or Without Doxycycline

Study Overview
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Brief Summary
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This randomized controlled superiority study will be conducted during 2023-2025. The eligible participants are adult people living with HIV (PLWH) who are newly diagnosed with early syphilis. Participants will be randomized in a 1:1 ratio to receive single-dose benzathine penicillin G (BPG) (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) or single-dose BPG. The primary outcome is serologic response, defined as a decline of rapid plasma reagin (RPR) titer by 4-fold or greater, at week 24 and week 48; and the secondary outcomes include microbiologic response of syphilis and bacterial sexually transmitted infections (STIs) assessed by nucleic-acid amplification test (NAAT) at week 4.

Official Title
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Comparisons of Treatment Responses of Early Syphilis to 2.4 Milliunits (MU) Single-dose Benzathine Penicillin G With or Without Doxycycline in People Living With HIV

Conditions
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Early Syphilis, Latent, Serological Relapse After Treatment

Intervention / Treatment
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* Drug: Benzathine Penicillin G
* Drug: Doxycycline Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: People living with HIV (PLWH) aged ≥18 years with early syphilis Confirmed by a positive RPR titer with a reactive TPPA assay Exclusion Criteria: PWH with RPR titers of <4 Exposure to antibiotics with activity against T. pallidum within the preceding 4 weeks (penicillin, 3rd cephalosporin, doxycycline, macrolides) A known or suspected infection requiring additional treatment with an antimicrobial active against T. pallidum (penicillin, 3rd cephalosporin, doxycycline, macrolides) Testing positive for C. trachomatis and M. genitalium, for which doxycycline or macrolide was administered A history of intolerance to penicillin or doxycycline PLWH have already participated in this study Pregnancy

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Active Comparator: single-dose BPG plus doxycycline<br>single-dose benzathine penicillin G (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) | Drug: Benzathine Penicillin G<br>* Benzathine Penicillin G (2.4 MU intramuscularly once)<br>Drug: Doxycycline Capsule<br>* doxycycline (100 mg orally twice daily for 7 days)<br>|
| Placebo Comparator: single-dose BPG<br>single-dose benzathine penicillin G (2.4 MU intramuscularly once) | Drug: Benzathine Penicillin G<br>* Benzathine Penicillin G (2.4 MU intramuscularly once)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serologic response | Either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive | Weeks 24 and week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiologic response of syphilis | T. pallidum PCR Ct value >38 | Week 4 | 
| Microbiologic response of bacterial STIs | negative STI PCR results | Week 4 | 
| Safety of study treatment |  | Week 4 | 
| Adherence evaluation of tablet intake |  | Week 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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syphilis, rapid plasma reagin