Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

National Taiwan University

Status and phase: Terminated; 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 sexually transmitted infections (STIs) among at-risk people living with HIV (PLWH), the prevalence of Chlamydia trachomatis and Neisseria 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 benzathine penicillin G (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: 109 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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109 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 million unit \[MU\] intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)

Treatment:

Drug: Doxycycline

Drug: benzathine penicillin G