Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

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)

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.

Study Overview

• Status: Terminated
• Conditions: Early Syphilis
• Intervention / Treatment: Drug: Doxycycline; Drug: Ceftriaxone; Drug: benzathine penicillin G

Detailed 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)

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taiwan
    • Taipei, Taiwan, Taiwan, 110
      • Kuan-Yin Lin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: single-dose ceftriaxone plus doxycycline; single-dose ceftriaxone (1g intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)	Drug: Doxycycline; doxycycline (100 mg orally twice daily for 7 days); Drug: Ceftriaxone; Ceftriaxone (1g intramuscularly once)
Active Comparator: single-dose BPG plus doxycycline; single-dose BPG (2.4 million unit [MU] intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)	Drug: Doxycycline; doxycycline (100 mg orally twice daily for 7 days); Drug: benzathine penicillin G; benzathine penicillin G (2.4 MU intramuscularly once)

What is the study measuring?

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 Month 3	Serologic response is defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive	Month 3
Rate of Serologic Response at Month 12	Serologic response is defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive	Month 12

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Kuan-Yin Lin, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2023
• Primary Completion (Actual): July 25, 2025
• Study Completion (Actual): July 25, 2025

Study Registration Dates

• First Submitted: March 8, 2023
• First Submitted That Met QC Criteria: July 31, 2023
• First Posted (Actual): August 8, 2023

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 22, 2026
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: gonorrhea; Treponema pallidum; chlamydia; sexually transmitted infection
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Chlamydiaceae Infections; Sexually Transmitted Diseases, Bacterial; Neisseriaceae Infections; Pathological Conditions, Signs and Symptoms; Sexually Transmitted Diseases; Chlamydia Infections; Gonorrhea; Syphilis; Treponemal Infections; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Amides; Naphthacenes; Tetracyclines; beta-Lactams; Lactams; Cephalosporins; Thiazines; Penicillins; Cefotaxime; Cephacetrile; Ceftriaxone; Doxycycline; Penicillin G
• Other Study ID Numbers: 202206138MIND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No