Linezolid for Syphilis Pilot Study

Phase 2

Recruiting

• Conditions: Syphilis
• Interventions: Drug: Group A, Penicillin; Drug: Group B, Linezolid 10d

• Registration Number: NCT05548426
• Lead Sponsor: University of Southern California

Brief Summary

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

Detailed Description

This will be a randomized, open-label, non-comparative, adaptive pilot trial to evaluate the efficacy of linezolid 600mg orally, twice a day, for five or 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.

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.

Study Timeline

• Study First Submitted: 2022-09-16
• Study First Submitted QC: 2022-09-16
• Study First Posted: 2022-09-21
• Study Start: 2023-09-28
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-13
• Last Update Posted: 2025-02-17
• Primary Completion: 2025-12
• Study Completion: 2026-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• 16 years of age or older
• Diagnosed cases of primary, secondary, or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment
• Able to provide informed consent
• For PLHIV: on treatment for HIV-infection and most recent viral load <200 copies/mL or most recent CD4 T-cell count >350 cells/mL

Exclusion Criteria

• Pregnancy or a positive pregnancy test on the day of enrollment
• Participants who receive certain psychotropic medications, e.g., MAO inhibitors, SNRIs, SSRIs
• Patients showing signs and symptoms of neurosyphilis
• Serofast RPR titer
• Recent (<7 days) or concomitant antimicrobial therapy with azithromycin, doxycycline, ceftriaxone, cefixime, or other beta lactam antibiotics (e.g. amoxicillin)
• Linezolid or penicillin allergy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

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

Trial Locations

Locations (2)

Howard Brown Health; 🇺🇸 Chicago, Illinois, United States

Open Arms HealthCare Center; 🇺🇸 Jackson, Mississippi, United States