Treatment Responses of Early Syphilis to Single-dose Ceftriaxone Plus Doxycycline Versus Single-dose Benzathine Penicillin G Plus Doxycycline in People Living With HIV (PLWH)
| Registry | NCT05980871 |
|---|---|
| Status | Terminated - An error of the sample size calculation occurred. A previous calculation based on a previous trial by Cao et al estimated to assign 150 participants to each group. A corrected calculation showed that 43 participants for each group is sufficient. |
| Phase | Phase 4 |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 109 (Actual) |
| Sponsor | National Taiwan University Hospital (Other) |
| Conditions | Early Syphilis |
| Interventions | Doxycycline, Ceftriaxone, benzathine penicillin G (Drug) |
| Dates | start 2023-03-10, primary completion 2025-07-25, completion 2025-07-25, first posted 2023-08-08, last updated 2026-02-25 |
| Locations | 1 site in Taiwan |
Related Papers Related Patents Related Grants Related Experts
All trials for Early Syphilis All trials of Doxycycline All trials of Ceftriaxone
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.
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)
| Arm | Type | Interventions | Description |
|---|---|---|---|
| single-dose ceftriaxone plus doxycycline | Active comparator | Drug: Doxycycline; Drug: Ceftriaxone | single-dose ceftriaxone (1g intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) |
| single-dose BPG plus doxycycline | Active comparator | Drug: Doxycycline; Drug: benzathine penicillin G | single-dose BPG (2.4 million unit \[MU\] intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) |
Sex: All, ages: 20 Years to any
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
| Milestone | CRO/Doxy | BPG/Doxy |
|---|---|---|
| Started | 56 | 53 |
| Completed | 56 | 53 |
| Not completed | 0 | 0 |
Time frame: from treatment to 1 week after treatment
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| CRO/Doxy | 0/56 (0.0%) | 0/56 (0.0%) | 26/56 (46.4%) |
| BPG/Doxy | 0/53 (0.0%) | 0/53 (0.0%) | 15/53 (28.3%) |
| Term | Organ system | CRO/Doxy | BPG/Doxy |
|---|---|---|---|
| Injection site pain or local swelling | Skin and subcutaneous tissue disorders | 24/56 | 11/53 |
| Jarisch-Herxheimer reaction | Immune system disorders | 10/56 | 2/53 |
| Diarrhea | Gastrointestinal disorders | 2/56 | 1/53 |
| Myalgia | Musculoskeletal and connective tissue disorders | 0/56 | 1/53 |
Limitations and caveats: The sample size calculation was based on a prior study with different dosing regimens and analytical strategies, which may have led to an overestimation of the efficacy with single-dose CRO and, consequently, affected the sample size estimation. The open-label design may have introduced bias. The absence of whole-genome sequencing limited the ability to distinguish treatment failure from reinfection. Routine CSF exams were not performed, potentially missing cases of asymptomatic neurosyphilis.
| Facility | City | Country | Status |
|---|---|---|---|
| Kuan-Yin Lin | Taipei, Taiwan | Taiwan |