Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

NCT05980871 | Terminated Phase 4 Results

• 1 other identifier: 202206138MIND
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Early Syphilis

Keywords

sexually transmitted infection; Treponema pallidum; gonorrhea; chlamydia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Rate of Microbiologic Response of Syphilis at Week 4

  Week 4

• Rate of Microbiologic Response of Bacterial STIs at Week 4

  Week 4

• Rate of Serologic Response at Month 3

  Month 3

• Rate of Serologic Response at Month 12

  Month 12

Study Arms (2)

single-dose ceftriaxone plus doxycycline

ACTIVE COMPARATOR

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

Drug: Doxycycline; Drug: Ceftriaxone

single-dose BPG plus doxycycline

ACTIVE COMPARATOR

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

Drug: Doxycycline; Drug: benzathine penicillin G

Interventions

benzathine penicillin G DRUG

benzathine penicillin G (2.4 MU intramuscularly once)

single-dose BPG plus doxycycline

Doxycycline DRUG

doxycycline (100 mg orally twice daily for 7 days)

single-dose BPG plus doxycycline; single-dose ceftriaxone plus doxycycline

Ceftriaxone DRUG

Ceftriaxone (1g intramuscularly once)

single-dose ceftriaxone plus doxycycline

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

Kuan-Yin Lin

Taipei, Taiwan, 110, Taiwan

Location

MeSH Terms

Conditions

Syphilis; Sexually Transmitted Diseases; Treponemal Infections; Gonorrhea; Chlamydia Infections

Interventions

Doxycycline; Ceftriaxone; Penicillin G

Condition Hierarchy (Ancestors)

Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sexually Transmitted Diseases, Bacterial; Communicable Diseases; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neisseriaceae Infections; Chlamydiaceae Infections

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Penicillins

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.

Results Point of Contact

• Title: Tzong-Yow Wu
• Organization: National Taiwan University Hospital Yunlin Branch

retep0102@gmail.com

886-933594074

Study Officials

• Kuan-Yin Lin

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2023
• First Posted: August 8, 2023
• Study Start: March 10, 2023
• Primary Completion: July 25, 2025
• Study Completion: July 25, 2025
• Last Updated: February 25, 2026
• Results First Posted: February 25, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)