Linezolid for Syphilis Pilot Study

Pilot Study of Linezolid for Early Syphilis Treatment

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

Study Overview

• Status: Active, not recruiting
• Conditions: Syphilis
• Intervention / Treatment: Drug: Group B, Linezolid 10d; Drug: Group A, Penicillin

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

1. Diagnosed cases of primary, secondary or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment
2. 16 years of age or older
3. Able to provide informed consent/assent.
4. Individuals with HIV infection must be on treatment for HIV-infection and virologically suppressed (viral load < 200 copies/mL) or have a CD4 count ≥ 350 cells/mm3 as of their most recent test prior to enrollment.

Exclusion Criteria include:

1. Pregnancy or a positive pregnancy test on the day of enrollment
2. Patients showing signs and symptoms of neurosyphilis.
3. Participants who receive certain psychotropic medications, e.g., MAO inhibitors, SNRIs, SSRIs
4. Serofast RPR titer, defined as persistently positive RPR titer without more than 4-fold (2-titer level) change for 12 months or greater.
5. 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)
6. Individuals with HIV infection who report HIV treatment interruption for more than 4 weeks since their most recent viral load or CD4 test.
7. Individuals with known myelosuppressive conditions or receiving myelosuppressive medication
8. Individuals weighing 150kg (330 lbs) or more.
9. Individuals with known end renal stage disease, for example individuals in hemodialysis.
10. Self-reported allergy to linezolid or penicillin.
11. Unwilling or unable to attend follow-up visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Linezolid 10 Day; Oral linezolid 600mg, taken twice a day for 10 days	Drug: Group B, Linezolid 10d; Oral Linezolid 600mg, taken twice a day for 10 days; Other Names: zyvox
Active Comparator: Benzathine Penicillin G; Single intramuscular injection of 2.4 million units of benzathine penicillin G	Drug: Group A, Penicillin; Standard of care benzathine penicillin G, one intramuscular injection, 2.4MU; Other Names: bicillin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treponema pallidum susceptibility	Determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of linezolid against 6 historical and 3 clinical isolated strains	6 months

Collaborators and Investigators

• Sponsor: University of Southern California
• Collaborators: The University of Texas Health Science Center, Houston; Universidad Peruana Cayetano Heredia
• Investigators: Principal Investigator: Jeffrey D Klausner, MD MPH, University of Southern California

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 16, 2022
• First Posted (Actual): September 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Penicillin; Linezolid; Treponema pallidum; Early Syphilis
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infections; Communicable Diseases; Sexually Transmitted Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Spirochaetales Infections; Sexually Transmitted Diseases, Bacterial; Syphilis; Treponemal Infections; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Azoles; Acids, Acyclic; Carboxylic Acids; Amides; Penicillin G; beta-Lactams; Lactams; Acetamides; Acetates; Oxazolidinones; Oxazoles; Linezolid; Penicillins; Penicillin G Benzathine
• Other Study ID Numbers: APP-22-04165

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No IPD will be shared with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No