Oral Doxycycline vs. Penicillin G or Ceftriaxone for Treatment of Neurosyphilis – Feasibility Study for a multicentric open-label randomized controlled trial

• Applicant: Dr. Johannes Camp
• Subject Area: Clinical Infectiology and Tropical Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 518674380

Syphilis is an infectious disease caused by the bacterium Treponema pallidum. The number of new infections with syphilis in Germany is increasing continuously. In 2019, 8,000 new infections were reported to the RKI. After the primary affect has passed, neurological manifestations can appear at any stage of syphilis. The clinical picture of neurosyphilis is very variable and ranges from syphilitic meningitis to the rare tabes doralis to uveitis caused by affection of the optic nerve. The gold standard of therapy is administration of penicillin G intravenously over 14 days. A retrospective observational study recently showed that ceftriaxone is associated with an outcome similar to that after therapy with penicillin G. There are also case collections that report favorable results after treatment of neurosyphilis with oral doxycycline. This therapy is therefore already recommended for patients with severe beta-lactam allergy, and administration of a dose of 2 x 200 mg doxycycline achieves treponemocidal concentrations in the cerebrospinal fluid. The favorable results of therapy with doxycycline in neuroborreliosis also make the non-inferiority of oral doxycycline therapy to intravenous penicillin administration seem plausible due to the relationship between B. burgdorferi and T. pallidum. Obvious advantages of an oral therapy option are lesser invasiveness (no venous access required), cost savings due to shorter/no hospitalization and easier availability. The aim of this feasibility study is to lay the foundation for conducting a randomized, multi-centre, non-inferiority trial in people with neurosyphilis. This follow-up study aims to assess the non-inferiority of oral treatment with doxycycline compared to standard intravenous treatment with penicillin G or ceftriaxone. The pilot study described here aims to set up a network for patient recruitment in multiple phases and to record the possible patient numbers and current treatment standards in the participating centers in a retrospective and prospective study phase. In addition, the case definition and treatment schemes are to be evaluated in a survey of the practitioners. In summary, the objectives of the pilot study applied for here are: Networking and identification/recruitment of potential study centers (national and international); Development and review of a pragmatic study design for a non-inferiority study; Retrospective (12 months) and prospective (4 months) recording of the incidence and the current "standard of care"

• DFG Programme: Research Grants