Comparisons of Treatment Responses of Early Syphilis to Benzathine Penicillin G With or Without Doxycycline

Comparisons of Treatment Responses of Early Syphilis to 2.4 Milliunits (MU) Single-dose Benzathine Penicillin G With or Without Doxycycline in People Living With HIV

This randomized controlled superiority study will be conducted during 2023-2025. The eligible participants are adult people living with HIV (PLWH) who are newly diagnosed with early syphilis. Participants will be randomized in a 1:1 ratio to receive single-dose benzathine penicillin G (BPG) (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days) or single-dose BPG. The primary outcome is serologic response, defined as a decline of rapid plasma reagin (RPR) titer by 4-fold or greater, at week 24 and week 48; and the secondary outcomes include microbiologic response of syphilis and bacterial sexually transmitted infections (STIs) assessed by nucleic-acid amplification test (NAAT) at week 4.

Study Overview

• Status: Not yet recruiting
• Conditions: Early Syphilis, Latent, Serological Relapse After Treatment
• Intervention / Treatment: Drug: Benzathine Penicillin G; Drug: Doxycycline Capsule

• Study Type: Interventional
• Enrollment (Estimated): 688
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kuan-Yin Lin, MD; Phone Number: +886975607715; Email: kuanyin0828@gmail.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• People living with HIV (PLWH) aged ≥18 years with early syphilis
• Confirmed by a positive RPR titer with a reactive TPPA assay

Exclusion Criteria:

• PWH with RPR titers of <4
• Exposure to antibiotics with activity against T. pallidum within the preceding 4 weeks (penicillin, 3rd cephalosporin, doxycycline, macrolides)
• A known or suspected infection requiring additional treatment with an antimicrobial active against T. pallidum (penicillin, 3rd cephalosporin, doxycycline, macrolides)
• Testing positive for C. trachomatis and M. genitalium, for which doxycycline or macrolide was administered
• A history of intolerance to penicillin or doxycycline
• PLWH have already participated in this study
• 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 BPG plus doxycycline; single-dose benzathine penicillin G (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)	Drug: Benzathine Penicillin G; Benzathine Penicillin G (2.4 MU intramuscularly once); Drug: Doxycycline Capsule; doxycycline (100 mg orally twice daily for 7 days)
Placebo Comparator: single-dose BPG; single-dose benzathine penicillin G (2.4 MU intramuscularly once)	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
Serologic response	Either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive	Weeks 24 and week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiologic response of syphilis	T. pallidum PCR Ct value >38	Week 4
Microbiologic response of bacterial STIs	negative STI PCR results	Week 4
Safety of study treatment		Week 4
Adherence evaluation of tablet intake		Week 4

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: China Medical University Hospital; Kaohsiung Medical University Chung-Ho Memorial Hospital; Taipei Veterans General Hospital, Taiwan; National Cheng-Kung University Hospital; Far Eastern Memorial Hospital; Chiayi Christian Hospital; Kaohsiung Veterans General Hospital.; Chi Mei Medical Hospital; National Taiwan University Hospital Hsin-Chu Branch; Taoyuan General Hospital; National Taiwan University Hospital, Yun-Lin Branch

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 1, 2023
• First Submitted That Met QC Criteria: October 1, 2023
• First Posted (Actual): October 5, 2023

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: syphilis; rapid plasma reagin
• Additional Relevant MeSH Terms: Infections; Communicable Diseases; Sexually Transmitted Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Latent Infection; Sexually Transmitted Diseases, Bacterial; Spirochaetales Infections; Treponemal Infections; Urogenital Diseases; Genital Diseases; Syphilis; Syphilis, Latent; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline; Penicillins; Penicillin G Benzathine; Penicillin G; Penicillin G Procaine
• Other Study ID Numbers: 202305061MINA

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