Linezolid vs Penicillin for Syphilis

Recruiting at 1 trial location

Overseen By Jeffrey D Klausner, MD MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Southern California

Must not be taking: MAO inhibitors, SNRIs, SSRIs

Disqualifiers: Pregnancy, Neurosyphilis, Serofast RPR, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1-2 weeks

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether linezolid, taken as a pill twice daily for 10 days, is as effective as a single penicillin injection for treating syphilis, a sexually transmitted infection. Researchers aim to determine if linezolid can serve as a viable alternative to penicillin, particularly for those unable to take penicillin. Individuals diagnosed with early-stage syphilis and recent syphilis test results showing certain activity levels may be suitable for this trial. Participants should not have received recent antibiotic treatment or have allergies to linezolid or penicillin. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain psychotropic medications and any recent or current antibiotics like azithromycin, doxycycline, or penicillin-related drugs before joining.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that linezolid is a safe antibiotic approved by the FDA. It typically treats various bacterial infections and is generally well-tolerated when taken as directed. Studies have found that linezolid can reach the brain, suggesting it might effectively treat brain infections.

Most people find linezolid safe, but some may experience mild side effects like nausea or headaches. Serious side effects are rare but can include changes in blood cell counts, so regular check-ups with a healthcare provider during treatment are important.

This study explores linezolid for treating syphilis. Since linezolid is already approved for other uses, this offers some reassurance about its safety. However, as with any medication, individual experiences can differ, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for syphilis?

Unlike the standard treatment for syphilis, which typically involves a single injection of benzathine penicillin G, Linezolid offers a unique oral option. Researchers are excited about Linezolid because it is administered as a pill, taken twice a day for 10 days, which could be more convenient for patients who have issues with injections or access to healthcare facilities. Additionally, Linezolid is known for its effectiveness against a range of bacterial infections, and its use in syphilis treatment could provide an alternative for individuals allergic to penicillin.

What evidence suggests that linezolid could be an effective treatment for syphilis?

This trial will compare Linezolid with Benzathine Penicillin G for treating syphilis. Research has shown mixed results for linezolid in treating syphilis. One study found that taking 600 mg of linezolid daily cured about 70% of early syphilis cases. However, another study found linezolid ineffective for early syphilis, meaning some patients improved while others did not. The effectiveness of linezolid for treating syphilis remains unclear and requires further research. ^{1 2 4 6 7}

Who Is on the Research Team?

Jeffrey D Klausner, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for individuals aged 16 or older diagnosed with primary, secondary, or early latent syphilis and have a recent RPR titer of at least 1:8. People living with HIV can join if they're on treatment and meet certain viral load or CD4 count criteria. Pregnant individuals, those on specific antibiotics or psychotropic meds, and anyone allergic to the study drugs cannot participate.

Inclusion Criteria

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

I am 16 years old or older.

Exclusion Criteria

Serofast RPR titer

Linezolid or penicillin allergy

I am showing signs of a brain or nerve condition caused by syphilis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linezolid 600mg orally, twice a day for either five or ten days

1-2 weeks

Follow-up

Participants are monitored for clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months

6 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Linezolid

Trial Overview

The study compares the effectiveness of two treatments for syphilis: Group A receives Penicillin (the standard treatment), while Group B gets Linezolid for 10 days. The goal is to see if Linezolid is an effective alternative.

How Is the Trial Designed?

Group I: Linezolid 10 Day Experimental Treatment 1 Intervention

Oral linezolid 600mg, taken twice a day for 10 days

Group II: Benzathine Penicillin G Active Control 1 Intervention

Single intramuscular injection of 2.4 million units of benzathine penicillin G

Linezolid is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Zyvox for:

• Complicated skin and skin structure infections
• Community-acquired pneumonia
• Nosocomial pneumonia
• Uncomplicated skin and skin structure infections

Approved in European Union as Zyvoxid for:

• Complicated skin and soft tissue infections
• Community-acquired pneumonia
• Nosocomial pneumonia

Approved in Canada as Zyvox for:

• Complicated skin and skin structure infections
• Community-acquired pneumonia
• Nosocomial pneumonia

Approved in Japan as Zyvox for:

• Complicated skin and soft tissue infections
• Community-acquired pneumonia
• Nosocomial pneumonia

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Universidad Peruana Cayetano Heredia

Collaborator

Trials

80

Recruited

62,300+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Published Research Related to This Trial

Benzathine penicillin remains the primary treatment for syphilis, as other options like clemizole and procaine penicillin are no longer available.

Alternative treatments such as doxycycline and ceftriaxone may be considered, but effective serological methods are essential to ensure the safety of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current syphilis therapies and serological control. Commentary on the article by M. Hartmann in Hautarzt, Volume 2 (2004)]. Heise, H.[2018]

Linezolid has demonstrated effectiveness against syphilis in animal studies, suggesting it could be a potential alternative treatment amid shortages of benzathine penicillin.

The review found no teratogenic effects of linezolid, and while some adverse effects were noted in animal studies, no adverse effects were reported in a limited number of human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Linezolid During Pregnancy. Navarro, S., Keith, K., Stafylis, C., et al.[2023]

In a study involving 28 patients with primary or secondary syphilis, both ceftriaxone and penicillin G were found to be equally effective in treating the infection, as evidenced by a significant decline in VDRL titers and resolution of clinical symptoms.

Ceftriaxone was well-tolerated with no adverse reactions reported, while one patient experienced an allergic reaction to penicillin G, suggesting that ceftriaxone may be a safer alternative for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone for the treatment of primary and secondary syphilis. Schöfer, H., Vogt, HJ., Milbradt, R.[2018]

Ceftriaxone showed a higher serological response rate than penicillin at the 6-month follow-up in treating syphilis, suggesting it could be a viable alternative for patients allergic to penicillin.

While ceftriaxone was found to be equally effective as penicillin overall, further large-scale, high-quality trials are needed to confirm its safety and efficacy as a substitute for penicillin in syphilis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies. Liu, M., Fan, Y., Chen, J., et al.[2023]

A meta-analysis of seven randomized controlled trials involving 639 subjects found that azithromycin is as effective as penicillin for treating syphilis, with no significant differences in response rates at 3, 6, or 12 months.

The study indicates that azithromycin does not show inferior efficacy compared to penicillin, suggesting it could be a viable alternative treatment for syphilis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin vs penicillin G benzathine for early syphilis: A meta-analysis of randomized controlled trials. Li, Y., Jiang, G.[2021]

A retrospective analysis of 138 patients treated with 1.5 g/day amoxicillin for syphilis showed a high serological cure rate of 94.9%, indicating its effectiveness as a treatment option.

The treatment was well-tolerated, with only 1.5% of patients changing therapy due to adverse events, suggesting that amoxicillin without probenecid is a safe alternative for patients with and without HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis. Ikeuchi, K., Fukushima, K., Tanaka, M., et al.[2022]

Azithromycin has been associated with treatment failures in syphilis due to a specific mutation in the Treponema pallidum bacteria that prevents the drug from effectively binding to its target, leading to increased resistance over time.

Despite the emergence of azithromycin resistance, Treponema pallidum remains sensitive to penicillin, highlighting the importance of using penicillin as the first-line treatment and the need for ongoing monitoring of antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin resistance in Treponema pallidum. Katz, KA., Klausner, JD.[2022]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11779243/

P-1378. Linezolid For Early Syphilis Treatment: Pilot study

Although a recent clinical study evaluating of 600mg Linezolid once daily for 5 days showed limited success, pharmacological simulations show ...

2.

academic.oup.com

academic.oup.com/ofid/article/12/Supplement_1/ofae631.1554/7989124

P-1378. Linezolid For Early Syphilis Treatment: Pilot study

The main outcome is a ≥4-fold RPR titer decline by 6 months after treatment. Linezolid participants are monitored for adherence and adverse ...

3.

thelancet.com

thelancet.com/journals/laninf/article/PIIS1473-3099(23)00683-7/fulltext

Oral linezolid compared with benzathine penicillin G for ...

In the current trial, treatment with 600 mg of linezolid once per day resulted in a cure rate of 70% among patients with early syphilis and did ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05548426

NCT05548426 | Linezolid for Syphilis Pilot Study

Study findings may identify an efficacious alternative syphilis treatment to penicillin that is effective for people living with HIV.

5.

cidrap.umn.edu

cidrap.umn.edu/antimicrobial-stewardship/linezolid-fails-early-syphilis-treatment-clinical-trial

Linezolid fails as early syphilis treatment in clinical trial

A randomized clinical trial conducted in Spain found that linezolid is not an effective treatment for patients with early syphilis.

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S1473309923006837

Oral linezolid compared with benzathine penicillin G for ...

In the current trial, treatment with 600 mg of linezolid once per day resulted in a cure rate of 70% among patients with early syphilis and did ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7973135/

Efficacy of linezolid on Treponema pallidum, the syphilis agent

In linezolid-treated animals, dark-field microscopy and qPCR assessment showed no presence of treponemes after day 3 post-treatment start, ...