Ceftriaxone compared with penicillin G for the treatment of neurosyphilis: study protocol for a multicenter randomized controlled trial

BACKGROUND: Neurosyphilis may cause irreversible neurological sequelae. First-line treatment consists of penicillin G, with ceftriaxone being an alternative treatment in patients allergic to penicillin. The lack of clinical data comparing the efficacy of these two drugs indicated the need for comparative clinical trials to improve national treatment guidelines in China. METHODS/DESIGN: In this multicenter randomized controlled clinical trial, 290 patients newly diagnosed with neurosyphilis will be randomized 1:1 to treatment with aqueous crystalline penicillin G (ACPG) or ceftriaxone. Patients will be treated with standard regimens of ACPG or ceftriaxone according to Chinese National Guidelines and will be followed up for 12 months. All clinical parameters will be assessed at baseline and at follow-up 3, 6, 9, and 12 months later. The primary outcomes will include cerebrospinal fluid (CSF) white blood cell (WBC) count, serological efficacy, and clinical efficacy. The secondary outcomes will include CSF protein concentrations, Mini-Mental State Examination (MMSE) scores, imaging results, recurrence, and time to recovery from neurosyphilis. Adverse events will be monitored and recorded during the trial. DISCUSSION: This trial will provide clinical data to determine whether ceftriaxone is non inferior to ACPG in treating neurosyphilis and will provide evidence for the improvement of treatment guidelines. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100047164. Registered on 9 June 2021 and updated on 23 November 2021.