Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

National Taiwan University

Status and phase: Active, not recruiting; Phase 4

Conditions: Early Syphilis

Treatments: Drug: benzathine penicillin G; Drug: Ceftriaxone; Drug: Doxycycline

Study type: Interventional

Funder types: Other

Identifiers

NCT05980871

202206138MIND

Details and patient eligibility

About

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.

Full description

Enrolled criteria:

1. PLWH aged 20 years or more
2. 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.
3. 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:

1. PLWH with RPR titers of less than 4
2. Exposure to antibiotics with activity against T. pallidum, such as penicillins, third-generation cephems, doxycycline, or macrolides, within the preceding 4 weeks
3. A known or suspected infection other than syphilis requiring additional treatment with an antimicrobial active against T. pallidum
4. A history of intolerance to penicillin, ceftriaxone, or doxycycline
5. 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:

1. Microbiologic response of syphilis (defined as T. pallidum PCR Ct value >38) at week 4
2. Microbiologic response of bacterial STIs (defined as negative PCR results) at week 4
3. Serologic response at months 3 and 12
4. 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.)
5. Adherence evaluation (the noting of tablet intake in the diary for the 7 days of the treatment period)

Enrollment: 300 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

single-dose ceftriaxone plus doxycycline

Active Comparator group

Description:

single-dose ceftriaxone (1g intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)

Treatment:

Drug: Doxycycline

Drug: Ceftriaxone

single-dose BPG plus doxycycline

Active Comparator group

Description:

single-dose BPG (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)

Treatment:

Drug: Doxycycline

Drug: benzathine penicillin G