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TerminatedNCT05980871Updated Feb 25, 2026Results posted

Treatment Responses of Early Syphilis to Ceftriaxone Plus Doxycycline

A Phase 4 interventional study of Doxycycline and Ceftriaxone in Early Syphilis, sponsored by National Taiwan University Hospital. Terminated at 1 site in Taiwan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2026-02-25.

Sponsored by National Taiwan University Hospital · Phase 4, Interventional, and Treatment

Why this study was 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
Enrollment
109
Allocation
Randomized
Ages
20 Years and older
Sex
All
01

Study 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.

Read the 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)
02

Conditions studied

  • Early Syphilis

Keywords

  • sexually transmitted infection
  • Treponema pallidum
  • gonorrhea
  • chlamydia
03

In context

Syphilis

126 studies on the registry are indexed under Syphilis; 34 are open to participants now.

This study's enrollment of 109 is below the median of 354 across 85 interventional studies indexed under Syphilis.

Browse Syphilis studies →

Lead sponsor

National Taiwan University Hospital is the lead sponsor of 2,615 studies on the registry; 576 are open to participants now.

Of its 11 completed or terminated interventional studies of FDA-regulated products, 2 (18%) have results posted.

Browse National Taiwan University Hospital studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion criteria

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
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
109 participants (actual)

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)

    Drug: Doxycycline · Drug: Ceftriaxone

  • 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 · Drug: benzathine penicillin G

Interventions

06

What researchers measure

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

    Time frame: Month 6

Secondary outcomes

  1. Rate of Microbiologic Response of Syphilis at Week 4

    Microbiologic response of syphilis is defined as T. pallidum PCR Ct value \>38

    Time frame: Week 4

  2. Rate of Microbiologic Response of Bacterial STIs at Week 4

    Microbiologic response of bacterial STIs is defined as negative PCR results

    Time frame: Week 4

  3. 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

    Time frame: Month 3

  4. 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

    Time frame: Month 12

07

Results

Posted Feb 25, 2026
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.

Participant flow

Recruitment started from March 10, 2023, to August 16, 2024. Participants were recruited from infectious diseases clinics at the National Taiwan University Hopsital, Taiwan.

Participant flow — Overall Study
MilestoneCRO/DoxyBPG/Doxy
Started5653
Completed5653
Not completed00

Outcome measures

PrimaryRate 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

Time frame:
Month 6
Reported as:
Count of participants · Participants
Rate of Serologic Response at Month 6
ParticipantsCRO/DoxyBPG/Doxy
Rate of Serologic Response at Month 63440
Statistical analysis
  • CRO/Doxy vs BPG/Doxy · Chi-squared · p = <0.05 · Risk difference (rd): -0.148 · 95% CI -0.32 to 0.025
SecondaryRate of Microbiologic Response of Syphilis at Week 4

Microbiologic response of syphilis is defined as T. pallidum PCR Ct value \>38

Time frame:
Week 4
Reported as:
Count of participants · Participants
Rate of Microbiologic Response of Syphilis at Week 4
ParticipantsCRO/DoxyBPG/Doxy
Rate of Microbiologic Response of Syphilis at Week 41720
SecondaryRate of Microbiologic Response of Bacterial STIs at Week 4

Microbiologic response of bacterial STIs is defined as negative PCR results

Time frame:
Week 4
Reported as:
Count of participants · Participants
Rate of Microbiologic Response of Bacterial STIs at Week 4
ParticipantsCRO/DoxyBPG/Doxy
Rate of Microbiologic Response of Bacterial STIs at Week 41613
SecondaryRate 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

Time frame:
Month 3
Reported as:
Count of participants · Participants
Rate of Serologic Response at Month 3
ParticipantsCRO/DoxyBPG/Doxy
Rate of Serologic Response at Month 33231
Statistical analysis
  • CRO/Doxy vs BPG/Doxy · Chi-squared · p = 0.887 · Risk difference (rd): -0.013 · 95% CI -0.199 to 0.172
SecondaryRate 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

Time frame:
Month 12
Reported as:
Count of participants · Participants
Rate of Serologic Response at Month 12
ParticipantsCRO/DoxyBPG/Doxy
Rate of Serologic Response at Month 123938
Statistical analysis
  • CRO/Doxy vs BPG/Doxy · Chi-squared · p = 0.814 · Risk difference (rd): -0.021 · 95% CI -0.191 to 0.15

Adverse events

Collected over from treatment to 1 week after treatment. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CRO/Doxy0/56 (0%)0/56 (0%)26/56 (46.4%)
BPG/Doxy0/53 (0%)0/53 (0%)15/53 (28.3%)
Most frequent other events
Most frequent other events
EventCRO/DoxyBPG/Doxy
Injection site pain or local swellingSkin and subcutaneous tissue disorders24/5611/53
Jarisch-Herxheimer reactionImmune system disorders10/562/53
DiarrheaGastrointestinal disorders2/561/53
MyalgiaMusculoskeletal and connective tissue disorders0/561/53

Baseline characteristics

Age, Continuous
Age, Continuous(years)CRO/DoxyBPG/DoxyTotal
Median38 (33 to 46)40 (35 to 46)39 (34 to 46)
Sex: Female, Male
Sex: Female, Male(Participants)CRO/DoxyBPG/DoxyTotal
Female000
Male5653109
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CRO/DoxyBPG/DoxyTotal
American Indian or Alaska Native000
Asian5653109
Native Hawaiian or Other Pacific Islander000
Black or African American000
White000
More than one race000
Unknown or Not Reported000
Receiving ART at baseline
Receiving ART at baseline(Participants)CRO/DoxyBPG/DoxyTotal
Count of participants5652108
CD4 count at baseline
CD4 count at baseline(cells/mm^3)CRO/DoxyBPG/DoxyTotal
Median556 (477 to 794)565 (446 to 733)558 (449 to 774)
08

Study locations

1 site
  • Kuan-Yin Lin
    Taipei, Taiwan 110, Taiwan
09

References and documents

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Mar 2023 to primary completion in Jul 2025, 28 months.

Results were first posted in Feb 2026, 7 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 8, 2023
First posted
Aug 8, 2023
StartActual
Mar 10, 2023
Primary completionActual
Jul 25, 2025
CompletionActual
Jul 25, 2025
Results first posted
Feb 25, 2026
Last update
Feb 25, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Feb 25, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05980871
Lead sponsor
National Taiwan University Hospital
Responsible party
Sponsor
First posted
Aug 8, 2023
Start date
Mar 10, 2023
Primary completion
Jul 25, 2025
Completion
Jul 25, 2025
Results posted
Feb 25, 2026
Last update
Feb 25, 2026

Study contacts

Kuan-Yin Lin
principal investigator · National Taiwan University Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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