Syphilis
Conditions
Interventions
Linezolid Tablets Group:Linezolid Tablets Oral 600 mg every 12 hours for 14 days
Aqueous Crystalline Penicillin G sodium Group:Intravenous ACPG 3-4 MU, every 4 hours, 18-24 million units/d, for 14 days
Sponsors
Hospital for Skin Diseases, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: To be eligible to participate in the study, a participant must meet the following criteria: 1. Aged 18 to 70 years at screening visit, any gender. 2. Asymptomatic or symptomatic neurosyphilis, ocular or otic syphilis, which includes one of the following (see Appendix 4 of research protocol for diagnostic criteria and further details on clinical presentation and specific assessments): (1) Asymptomatic neurosyphilis in the context of treatment failure evidenced by a non-fourfold decrease in serum rapid plasma reagin (RPR) or toluidine red unheated serum test (TRUST) titer within one or two years of treatment for early or late syphilis, respectively, without suspicion of reinfection and/or high risk HIV (CD45 cells/µL o CSF protein concentration >45 mg/dL (2)In HIV individuals, as HIV itself causes mild CSF pleocytosis, meeting at least 1 out of following 4 criteria: o CSF-VDRL or CSF-RPR or CSF-TRUST reactive o CSF-WBC >20 cells/µL o CSF-WBC >5 cells/µL and CD4 5 cells/µL and CD4 >=200 cells/ µL and reactive CSF-treponemal test In the context of ocular or otic syphilis, both in non-HIV and HIV individuals, reactive CSF laboratory criteria are not required if clinical findings are consistent. Nonetheless, CSF abnormalities, when present, will be useful to assess the effect of treatment. The non-treponemal test titer threshold of 1:8 is used to confirm active infection and to allow reliable serologic monitoring of treatment response. The >=1:8 cutoff allows accurate evaluation of the primary efficacy endpoint, defined as a >=4-fold decline in non-treponemal titer at follow-up. Lower titers (<1:8) may persist without significant change due to the serofast state and would introduce a con
Exclusion criteria
Exclusion criteria: 1. Known allergy to linezolid, penicillin, and/or excipients, particularly known hypersensitivity to penicillin, cephalosporins, or other beta-lactam agents and/or allergy to soya or peanut. 2. Lactose or galactose intolerance or glucose-galactose malabsorption. 3. Pregnant or breastfeeding women, or willing to be pregnant during the follow-up period. 4. Current treatment with any drugs likely to interact with the study medication (see list in Appendix 2 of the research protocol). 5. Have been treated with any investigational chemical or biologic agent or currently enrolled in another interventional clinical study for at least 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug. 6. Have taken any antibiotics with potential activity against syphilis (e.g. beta lactams, cephalosporines, macrolides, tetracyclines) within 1 week prior to randomization or have been administered intramuscular penicillin within 2 weeks prior to randomization. 7. Myelosupression, defined as any of the following: o Absolute neutrophil count (ANC) 2 weeks. Exclusion aims to minimize safety risks and to avoid confounding effects on immune response and treatment outcomes. Patients with controlled HIV infection (stable on ART and undetectable viral load) may be included, as this group has comparable clinical responses to neurosyphilis therapy based on published evidence. 11. Active or inadequately treated tuberculosis. 12. Current or past history (in the last year) of advanced malignancy 13. Uncontrolled hypertension, pheochromocytoma or hyperthyroidism
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite endpoint of cure: Clinical cure (only for ocular syphilis), CSF Test of Cure and Serological cure; | — |
Secondary
| Measure | Time frame |
|---|---|
| Rates of clinical(only for ocular syphilis), Cerebrospinal Fluid and serological cure separately;Proportion of participants with adverse events and description of severity. ;Area under the plasma concentration - time curve for 24 h (AUC24h) of linezolid derived from observed pharmacokinetic profile data. ;Linezolid CSF:plasma concentration ratio, based on matched plasma and CSF samples. ; | — |
Countries
China
Contacts
Public ContactWujian Ke
Hospital for Skin Diseases, Chinese Academy of Medical Sciences
Outcome results
None listed