Early shift to oral antibiotic treatment for pyogenic vertebral osteomyelitis (SAVE): study protocol for an open label, non-inferiority, nation-wide randomized controlled clinical trial.

BACKGROUND: The current Danish National Guideline (DNG) for treatment of pyogenic vertebral osteomyelitis (PVO) recommends 6 weeks antibiotic (AB) treatment, with a 2-week intravenous (IV) AB lead-in followed by 4 weeks oral AB for uncomplicated PVO, and 12 weeks AB treatment with a 4-week IV AB lead-in followed by 8 weeks oral AB for complicated PVO. The primary objective of the current study is to investigate whether shortening the duration of IV AB to one week is non-inferior to the current DNG. METHODOLOGY: The SAVE trial is an investigator initiated, randomized (1:1), controlled, non-inferiority, parallel group, open-label trial. Patients will be included at departments of infectious diseases in Denmark. All adult patients diagnosed with and treated for PVO will be assessed for eligibility. Patients will be eligible for inclusion if they fulfill all the inclusion and none of the exclusion criteria. Exclusion criteria include among others previous episodes of PVO within the past 24 months, spinal implants inserted prior to current episode of PVO, other infectious foci necessitating >7 days of IV AB, identification of selected bacteria as well as fungi as the etiology and severe immunocompromise. Patients will be randomized if their C-reactive protein (CRP) has decreased to <75% of peak value or to <20 mg/l by day 7 of appropriate IV AB. Five-hundred thirty patients will be included and randomized. The primary endpoint is a composite of all-cause mortality, unplanned surgical intervention in relation to the spine and related to PVO, relapse of bacteremia with the primary pathogen, relapse of bacteria by culture with the initial pathogen being cultured from relevant material from infected areas in relation to the spine or iliopsoas muscle (detected by culture), renewed course of IV ABs given for >7 days for treatment of PVO. The primary endpoint will be adjudicated by a blinded end-point committee. DISCUSSION: If early transition to oral therapy is found non-inferior to the current DNG, it will provide the basis for shortening hospitalization, reducing costs, and increasing patient autonomy. TRIAL REGISTRATION: European Union Clinical Trials - EU CT Number 2023-507617-96-01: First approval 27/11/2023. Link:  https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2023-507617-96-01 .