Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

Study Overview
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Brief Summary
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In a prospective study investigating the prevalence of STIs among at-risk PLWH, the prevalence of Chlamydia trachomatis and N. gonorrhoeae was 24.7% and 12.1%, respectively. Surprisingly, the study found high rates of C. trachomatis and/or N. gonorrhoeae co-infections in PLWH with recent hepatitis C virus (HCV) infection (50%), HBsAg positivity (44%), and early syphilis (36%). Considering the high rate of sexually transmitted co-infections, combination therapy of single-dose ceftriaxone plus 7-day doxycycline for early syphilis may provide convenience and benefit to treatment of N. gonorrhoeae and C. trachomatis co-infections at a single clinic encounter. In the present study, this study aim to compare the efficacy of ceftriaxone plus doxycycline versus BPG plus doxycycline as the treatment for early syphilis among PLWH.

Detailed Description
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Enrolled criteria: PLWH aged 20 years or more PLWH with early syphilis (i.e. primary, secondary, or early latent syphilis), confirmed by a positive rapid plasma reagin (RPR) titer with a reactive Treponema pallidum particle agglutination (TPPA) assay. PLWH has provided informed consent *A participant with repeated syphilis can be repeated enrolled after signing an informed consent if the previous episode of early syphilis was successfully treated with achieving at least a 4-fold decrease in RPR titers and 48-week follow-up is completed. Exclusion criteria: PLWH with RPR titers of less than 4 Exposure to antibiotics with activity against T. pallidum, such as penicillins, third-generation cephems, doxycycline, or macrolides, within the preceding 4 weeks A known or suspected infection other than syphilis requiring additional treatment with an antimicrobial active against T. pallidum A history of intolerance to penicillin, ceftriaxone, or doxycycline Pregnancy Primary outcome: Serologic response at month 6 (defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive) Secondary outcomes: Microbiologic response of syphilis (defined as T. pallidum PCR Ct value >38) at week 4 Microbiologic response of bacterial STIs (defined as negative PCR results) at week 4 Serologic response at months 3 and 12 Safety of study treatment recorded by using a diary (all adverse events will be coded and graded according to Common Terminology Criteria for Adverse Events [CTCAE] v4.0.) Adherence evaluation (the noting of tablet intake in the diary for the 7 days of the treatment period)

Official Title
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Treatment Responses of Early Syphilis to Single-dose Ceftriaxone Plus Doxycycline Versus Single-dose Benzathine Penicillin G Plus Doxycycline in PLWH

Conditions
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Early Syphilis

Intervention / Treatment
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* Drug: Doxycycline
* Drug: Ceftriaxone
* Drug: benzathine penicillin G


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PLWH aged 20 years or more PLWH with early syphilis (i.e. primary, secondary, or early latent syphilis), confirmed by a positive rapid plasma reagin (RPR) titer with a reactive Treponema pallidum particle agglutination (TPPA) assay. PLWH has provided informed consent Exclusion Criteria: PLWH with RPR titers of less than 4 Exposure to antibiotics with activity against T. pallidum, such as penicillins, third- generation cephems, doxycycline, or macrolides, within the preceding 4 weeks A known or suspected infection other than syphilis requiring additional treatment with an antimicrobial active against T. pallidum A history of intolerance to penicillin, ceftriaxone, or doxycycline Pregnancy

Ages Eligible for Study
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Minimum Age: 20 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 ceftriaxone plus doxycycline<br>single-dose ceftriaxone (1g intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) | Drug: Doxycycline<br>* doxycycline (100 mg orally twice daily for 7 days)<br>Drug: Ceftriaxone<br>* Ceftriaxone (1g intramuscularly once)<br>|
| Active Comparator: single-dose BPG plus doxycycline<br>single-dose BPG (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) | Drug: Doxycycline<br>* doxycycline (100 mg orally twice daily for 7 days)<br>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 |
| --- | --- | --- |
| Rate of serologic response at month 6 | Serologic response is defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of microbiologic response of syphilis at week 4 | Microbiologic response of syphilis is defined as T. pallidum PCR Ct value >38 | Week 4 | 
| Rate of microbiologic response of bacterial STIs at week 4 | Microbiologic response of bacterial STIs is defined as negative PCR results | Week 4 | 
| Rate of serologic response at months 3 and 12 | Serologic response is defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive | Months 3 and 12 |