Alternative Antibiotics for Syphilis

July 17, 2025 updated by: Oriol Mitja, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Oral and Neuro-Penetrative Alternative Antibiotics for Patients With Syphilis

The Trep-AB clinical trial will test the efficacy of an investigational neuropenetrative drug, Linezolid (LZD), compared to standard treatment, Benzathine penicillin G (BPG), for early syphilis in humans. The overarching idea of the work proposed herein is to investigate the use of LZD to treat syphilis, conducting a randomized controlled clinical trial to evaluate this new indication of a known antibacterial agent.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The syphilis epidemic is rampant around the world, and therapeutic options are restricted to an antibiotic, intramuscular (IM) BPG, which does not efficiently cross the blood-brain barrier. Treponema pallidum (T.p.), the bacteria that causes syphilis, invades the central nervous system (CNS) in 40% of patients, usually without symptoms. The prognostic implications of CNS invasion are the potential for severe neurologic complications, and treatment failure due to sequestered bacteria in the CNS. When indicated, the only way to identify and treat neurosyphilis is by lumbar puncture to examine the cerebrospinal fluid (CSF), followed by intravenous (IV) Benzyl penicillin therapy. The invetigators have carried out in silico studies showing that oxazolidinones are potentially active against T.p., are neuropenetrative and can be administered orally. The invetigators have carried out preclinical studies using an in vitro culture system for T.p. and the use of the syphilis animal model with rabbits to test different antibiotics. The invetigators have confirmed that LZD was the best compound that could go on to be tested in clinical trials to treat syphilis.

The Trep-AB clinical trial will test the efficacy of an investigational neuropenetrative drug, LZD, compared to standard treatment BPG, for early syphilis in humans conducting a randomized controlled clinical. Primary objective is to demonstrate the non-inferiority of LZD treatment compared with standard BPG treatment to cure patients with early syphilis. Seconday objective is to isolate T.p. strains in clinical samples to subtype DNA from patients at baseline and during recurrence or treatment failure.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
224

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Spain
      • Barcelona, Spain, 08036
        • Hospital Clínic de Barcelona
      • Barcelona, Spain, 08916
        • Hospital Germans Trias Pujol
      • Barcelona, Spain, 08001
        • CAP Drassanes-Hospital Universitari Vall d'Hebron
      • Barcelona, Spain, 08015
        • Barcelona Checkpoint
      • Madrid, Spain
        • Hospital 12 de Octubre
  • United Kingdom
      • London, United Kingdom
        • Mortimer Market Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age 18 years or older at baseline visit.

  2. Primary, secondary or early latent syphilis diagnosis based on SEIMC/IUSTI Guidelines*

    1. Primary syphilis is defined as typical ulcer (chancre) and positive test using darkfield examination (DFE) or Polymerase chain reaction (PCR) detection of T.p. with/without positive serological test for syphilis.
    2. Secondary syphilis is defined based on typical clinical symptoms with positive treponemal and non-treponemal tests.
    3. Early latent syphilis is defined as positive serological treponemal and non-treponemal tests with no clinical evidence of infection, with a previous negative syphilis serology,or a four-fold increase in RPR titer of a non-treponemal test within the past 12 months.Serological tests for syphilis performed within 10 days prior to study inclusion visit willbe acceptable for enrollment.
  3. Signature of written informed consent.
  4. Ability to comply with the requirements of the study protocol.
  5. If women of childbearing potential, use of a highly effective method of contraception (abstinence,hormonal contraception, intra-uterine device [IUD], or anatomical sterility in self or partner)committed during 1 week after last IMP administration.

  6. If men, use of condom during heterosexual intercourse and use of a highly effective method ofcontraception (abstinence, hormonal contraception, intra-uterine device [IUD], or anatomical sterilityin self or partner) in female partner committed during 1 week after last IMP administration.

    • For inclusion purposes, positive point of care tests (POCT) will be accepted in selected patients without previous syphilis history and negative serological tests for syphilis during the last 12 months (Syphilis rapid diagnostic test [RDT] or Chembio DPP syphilis screen & confirm assay [DPP]), or with a previous history of syphilis and negative non-treponemal tests during the last 12 months (DPP). Further confirmation by the methods described in a), b) or c) will benecessary.

Exclusion Criteria:

  1. Known allergy to any of the IMPs and/or excipients, particularly known hypersensitivity to penicillin, cephalosporins or other beta-lactam agents and/or allergy to soya or peanut.
  2. Lactose or galactose intolerance or glucose-galactose malabsorbtion.
  3. Diagnosis criteria of symptomatic neurosyphilis.
  4. Pregnant or breastfeeding women.
  5. Current treatment with any drugs likely to interact with the study medication (see Appendix 6).
  6. Have taken any antibiotics with potential activity against syphilis (e.g. beta lactams, cephalosporines, macrolides, tetracyclines) within 1 week prior to randomization.
  7. Uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome, bipolar disorder, incapacitating psycho-affective disturbance, acute confusional state.
  8. Renal function impairment requiring hemodialysis.
  9. Symptomatic concomitant STI (i.e., gonococcus, chlamydia, lymphogranuloma venereum, Mycoplasma genitalium) or other infection disease requiring antibiotic treatment potentially active against syphilis.
  10. Having received treatment for the early syphilis recently diagnosed (In the previous 6 months)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Linezolid (LZD) 1200
Patients will take film coated tables of LZD 600 mg every 12 hours during 10 days
Drug: Linezolid 600 mg
After randomized to the experimental arm, the patient will take 1 tablet of Linezolid every 12hours during 10 days or 1 tablet of of Linezolid every 24hours during 5 days.
Active Comparator: Benzathine Penicillin G (BPG)
Administration of intramuscular BPG 2.4 MIU single dose during day 1
Drug: Benzathine Penicilllin G
After randomized to the control arm, the patient will receive a single dose of intramuscular BPG.
Experimental: Linezolid (LZD) 600
Patients will take film coated tables of LZD 600 mg every 24 hours during 5 days
Drug: Linezolid 600 mg
After randomized to the experimental arm, the patient will take 1 tablet of Linezolid every 12hours during 10 days or 1 tablet of of Linezolid every 24hours during 5 days.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Proportion of patients with clinical resolution of primary syphilis lesions (clinical cure, primary).
Time Frame: at week 2
Assesment of clinical resolution defined as the complete healing of primary syphilis lesions within 2 weeks from treatment start.
at week 2
Proportion of patients with clinical resolution of secondary syphilis lesions (clinical cure, secondary).
Time Frame: at week 6
Assesment of clinical resolution defined as the complete healing of secondary syphilis lesions within 6 weeks from treatment start.
at week 6
Proportion of patients with adequate serological response (serological cure, week 12).
Time Frame: at week 12
Assessment of adequate serological response defined as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion to negative.
at week 12
Proportion of patients with adequate serological response (serological cure, week 24).
Time Frame: at week 24
Assessment of adequatesserological response defined as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion to negative.
at week 24
Proportion of patients with adequate serological response (serological cure, week 48).
Time Frame: at week 48
Assessment of adequate serological response defined as a four-fold decline in rapid plasma reagin (RPR) titer or seroreversion to negative.
at week 48
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in recurrent syphilis or suspected treatment failure (molecular cure).
Time Frame: From date of randomization until date of first documented recurrence or treatment failure, assesed up to 48 weeks
Assessment of re-infection in recurrent syphilis as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS).
From date of randomization until date of first documented recurrence or treatment failure, assesed up to 48 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in ulcer or mucosa lesions swabs (re-infection).
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assessment of re-infection in recurrent syphilis lesions as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS).
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in plasma (re-infection).
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assessment of re-infection in recurrent syphilis (secondary or early latent) as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS).
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in oral swab/saliva (re-infection).
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assessment of re-infection in recurrent syphilis (secondary or early latent) as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS).
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in skin punch biopsy (re-infection).
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assessment of re-infection in recurrent syphilis lesions as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS).
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of patients with allelic variation in T. pallidum strain(s) DNA in ear lobe scraping (re-infection).
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assessment of re-infection in recurrent syphilis (secondary or early latent) as defined by allelic variation in core genes of T. pallidum strain(s) compared to baseline using a molecular method (MLST-WGS). (Optional,in a selected group of patients).
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of patients with suspicion of neurosyphilis that have allelic variation in Treponema pallidum (T.p) isolates DNA in CSF (re-infection).
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assessment of re-infection in patients with suspicion of neurosyphilis as defined by allelic variation in core genes of T. pallidum strains compared to baseline using a molecular method (MLST-WGS). (in a selected group of patients with suspicion of neurosyphilis).
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of patients with antibiotic resistance genotype.
Time Frame: From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Assesment of allelic variation in core genes conferring antimicrobial resistance in clinical specimens from patients who are considered to have treatment failure compared to patients with adequate clinical and serological response.
From date of randomization until date of first documented recurrence, assesed up to 48 weeks
Proportion of participants experiencing adverse events.
Time Frame: up to 12 weeks
Assesment of adverse events related to LZD treatment compared with adverse events related to standard BPG treatment in participants with early syphilis.
up to 12 weeks
Proportion of patients who have a change in the RPR titer within 2 weeks after treatment start of primary syphilis.
Time Frame: at 2 weeks
Assessment of RPR titer variation at week 2 from treatment start of patients with primary syphilis.
at 2 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Oriol Mitjà Villar, PhD, Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 14, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 16, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 5, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 6, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Trep-AB
  • 2020-005604-19 (EudraCT Number)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Primary Syphilis

Clinical Trials on Benzathine Penicilllin G

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings