Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

• ClinicalTrials.gov Identifier: NCT05980871
• Recruitment Status: Recruiting
• First Posted: August 8, 2023
• Last Update Posted: August 8, 2023
• Sponsor: National Taiwan University Hospital
• Information provided by (Responsible Party): National Taiwan University Hospital

Tracking Information

• First Submitted Date: March 8, 2023
• First Posted Date: August 8, 2023
• Last Update Posted Date: August 8, 2023
• Actual Study Start Date: March 10, 2023
• Estimated Primary Completion Date: March 15, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 31, 2023)

Rate of serologic response at month 6 [ Time Frame: Month 6 ]

Serologic response is defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: July 31, 2023)

• Rate of microbiologic response of syphilis at week 4 [ Time Frame: Week 4 ]
  Microbiologic response of syphilis is defined as T. pallidum PCR Ct value >38
• Rate of microbiologic response of bacterial STIs at week 4 [ Time Frame: Week 4 ]
  Microbiologic response of bacterial STIs is defined as negative PCR results
• Rate of serologic response at months 3 and 12 [ Time Frame: Months 3 and 12 ]
  Serologic response is defined as either a 4-fold or greater decline in RPR titer compared to baseline or being RPR-nonreactive

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline
• Official Title: Treatment Responses of Early Syphilis to Single-dose Ceftriaxone Plus Doxycycline Versus Single-dose Benzathine Penicillin G Plus Doxycycline in PLWH
• Brief Summary: In a prospective study investigating the prevalence of STIs among at-risk PLWH, the prevalence of Chlamydia trachomatis and N. 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 BPG plus doxycycline as the treatment for early syphilis among PLWH.

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
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Early Syphilis

Intervention

• Drug: Doxycycline
  doxycycline (100 mg orally twice daily for 7 days)
• Drug: Ceftriaxone
  Ceftriaxone (1g intramuscularly once)
• Drug: benzathine penicillin G
  benzathine penicillin G (2.4 MU intramuscularly once)

Study Arms

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

  • Drug: Doxycycline
  • Drug: Ceftriaxone
• Active Comparator: single-dose BPG plus doxycycline
  single-dose BPG (2.4 MU intramuscularly once) plus doxycycline (100 mg orally twice daily for 7 days)
  Interventions:

  • Drug: Doxycycline
  • Drug: benzathine penicillin G

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 31, 2023): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 15, 2025
• Estimated Primary Completion Date: March 15, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Kuan-Yin Lin; +886975607715; kuanyin0828@gmail.com

• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT05980871
• Other Study ID Numbers: 202206138MIND
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: National Taiwan University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: National Taiwan University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kuan-Yin Lin; National Taiwan University Hospital

• PRS Account: National Taiwan University Hospital
• Verification Date: March 2023