CompletedNCT05548426Updated Nov 4, 2026

Linezolid for Syphilis Pilot Study

A Phase 2 interventional study of Group B, Linezolid 10d and Group A, Penicillin in Syphilis, sponsored by University of Southern California. Completed at 5 sites in United States. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2026-11-04.

Sponsored by University of Southern California · Phase 2, Interventional, and Treatment

Updated Nov 4, 2026Now CompletedPrimary completion moved+2 moreGo to Updates ↓

Phase: Phase 2
Study type: Interventional
Enrollment: 24
Allocation: Randomized
Ages: 16 Years and older
Sex: All

Study summary

The study aims to evaluate the efficacy of linezolid for the treatment of syphilis.

Read the detailed description

This will be a randomized, open-label, non-comparative, pilot trial to evaluate the efficacy of linezolid 600mg orally, twice a day, for ten days, using a contemporaneous historical control group benzathine penicillin G (single dose of 2.4 million units) in participants with and without HIV infection.

In total, 24 participants will be enrolled across multiple clinical sites in the United States. Participants will participate in follow-ups to monitor clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months. A 5 and 10-day phone call will ensure adherence to treatment and evaluate safety.

Study findings may identify an efficacious alternative syphilis treatment to penicillin that is effective for people living with HIV. Study findings may also help address the crisis of penicillin shortages, difficulty in administration, and offer options for those with penicillin allergy.

Conditions studied

Syphilis

Browse trials for

Syphilis 126

Keywords

Linezolid
Treponema pallidum
Penicillin
Early Syphilis

In context

Syphilis

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

This study's enrollment of 24 is below the median of 354 across 85 interventional studies indexed under Syphilis.

Browse Syphilis studies →

Lead sponsor

University of Southern California is the lead sponsor of 791 studies on the registry; 136 are open to participants now.

Of its 70 completed or terminated interventional studies of FDA-regulated products, 32 (46%) have results posted.

Browse University of Southern California studies →

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

Who can participate

Ages eligible: 16 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria: To be eligible for this study, participants must be:

Diagnosed cases of primary, secondary or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment
16 years of age or older
Able to provide /assent.
Individuals with infection must be on treatment for HIV-infection and virologically suppressed (viral load \< 200 copies/mL) or have a ≥ 350 cells/mm3 as of their most recent test prior to enrollment.

Exclusion Criteria include:

Pregnancy or a positive pregnancy test on the day of enrollment
Patients showing signs and symptoms of neurosyphilis.
Participants who receive certain psychotropic medications, e.g., MAO inhibitors, SNRIs, SSRIs
Serofast RPR titer, defined as persistently positive RPR titer without more than 4-fold (2-titer level) change for 12 months or greater.
Recent (within the past 7 days) or concomitant antimicrobial therapy with activity against syphilis, namely azithromycin, tetracycline, doxycycline, cefixime, ceftriaxone or other beta lactam antibiotics (e.g. amoxicillin)
Individuals with HIV infection who report HIV treatment interruption for more than 4 weeks since their most recent viral load or CD4 test.
Individuals with known myelosuppressive conditions or receiving myelosuppressive medication
Individuals weighing 150kg (330 lbs) or more.
Individuals with known end renal stage disease, for example individuals in hemodialysis.
Self-reported allergy to linezolid or penicillin.
Unwilling or unable to attend follow-up visits.

Terms in these criteria, in plain language(3)

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.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 24 participants (actual)

Study arms

Experimental
Linezolid 10 Day
Oral linezolid 600mg, taken twice a day for 10 days
Drug: Group B, Linezolid 10d
Active comparator
Benzathine Penicillin G
Single intramuscular injection of 2.4 million units of benzathine penicillin G
Drug: Group A, Penicillin

Interventions

DrugGroup B, Linezolid 10d
Oral Linezolid 600mg, taken twice a day for 10 days
Also known as: zyvox
DrugGroup A, Penicillin
Standard of care benzathine penicillin G, one intramuscular injection, 2.4MU
Also known as: bicillin

What researchers measure

Primary outcomes

Response to Treatment
Percentage of linezolid participants with a 4-fold decrease or greater in the serum RPR titer by 180 days after treatment
Time frame: 6 months

Study locations

5 sites

Howard Brown Health
Chicago, Illinois 60613, United States
Open Arms HealthCare Center
Jackson, Mississippi 39216, United States
University of Mississippi Medical Center
Jackson, Mississippi 39216, United States
Wake Forest Baptist Health
Greensboro, North Carolina 27405, United States
Open Door Health
Providence, Rhode Island 02907, United States

References and documents

Individual participant data

Plan to share: No — No IPD will be shared with other researchers

No publications or documents are linked to this record.

Timeline

1 registry update since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedDate before it movedWhere the date was before it moved

Ran from Sep 2023 to primary completion in Sep 2026, 36 months.

Since we started tracking on Sep 25, 2026, the dates moved once, on Nov 4, 2026: primary completion Aug 2026 → Sep 2026 and completion Aug 2026 → Oct 2026.

Earlier changes are on the record history on ClinicalTrials.gov ↗

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

Registered: Sep 16, 2022
First posted: Sep 21, 2022
StartActual: Sep 28, 2023
Primary completionActual: Sep 30, 2026was Aug 2026
CompletionActual: Oct 30, 2026was Aug 2026
Last update: Nov 4, 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.

Status

Active, not recruiting→Completed

changed Nov 4, 2026

Primary completion

Aug 2026→Sep 30, 2026 (actual)

Nov 4, 2026

Study completion

Aug 2026→Oct 30, 2026 (actual)

Nov 4, 2026

Show all 1 update

Nov 4, 2026
Active, not recruiting→Completed
Primary completion Aug 2026→Sep 30, 2026 (now actual)
Study completion Aug 2026→Oct 30, 2026 (now actual)
+ 1 other change: verification date

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05548426
Lead sponsor: University of Southern California
Responsible party: Jeffrey D Klausner (Clinical Professor, University of Southern California) — Principal investigator
First posted: Sep 21, 2022
Start date: Sep 28, 2023
Primary completion: Sep 30, 2026
Completion: Oct 30, 2026
Last update: Nov 4, 2026

Study contacts

Jeffrey D Klausner, MD MPH

principal investigator · University of Southern California

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Nov 2026. You cannot join it, but the record below documents what was studied.

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