Linezolid Pilot Study

Sponsor

University of Southern California (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05548426

Collaborator

Universidad Peruana Cayetano Heredia (Other), The University of Texas Health Science Center, Houston (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The two specific aims are: AIM 1: To evaluate the efficacy of linezolid compared to benzathine penicillin G in the treatment of syphilis. AIM 2: Evaluate the susceptibility of Treponema pallidum historical and novel strains to linezolid.

Condition or Disease	Intervention/Treatment	Phase
Syphilis	Drug: Group C, Linezolid 5 Drug: Group B, Linezolid 10d Drug: Group A, Penicillin	Early Phase 1

Detailed Description

This will be a randomized, open-label, non-comparative, adaptive pilot trial to evaluate the efficacy of two linezolid oral dosing schemes (600mg orally, twice a day, for five or ten days) compared to the current recommendation for the treatment of syphilis, benzathine penicillin G (single dose of 2.4 million units) in participants with and without HIV infection. In total, 60 participants will be enrolled across 2 clinical sites in Peru. Participants will participate in follow-ups to monitor clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months. We will also test linezolid against several types of syphilis strains in the lab to evaluate the microbicidal activity of linezolid in treating early syphilis. 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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pilot Study of Linezolid for Early Syphilis Treatment

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Mar 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Linezolid 5 Day Oral Linezolid 600mg, taken twice a day for 5 days	Drug: Group C, Linezolid 5 Oral Linezolid 600mg, taken twice a day for 5 days
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
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

Arm

Intervention/Treatment

Experimental: Linezolid 5 Day

Oral Linezolid 600mg, taken twice a day for 5 days

Drug: Group C, Linezolid 5

Oral Linezolid 600mg, taken twice a day for 5 days

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

Treponema pallidum susceptibility [6 months]
Determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of linezolid against 6 historical and 3 clinical isolated strains

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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