Early Switch to Oral Antibiotics Versus Standard Delayed Switch in Adults with Pyogenic Vertebral Osteomyelitis: A Multicenter Randomized Non‑Inferiority Trial (sWITCH‑VO)

The primary objective is to establish the non-inferiority of an early transition from intravenous to oral antibiotic therapy after 7 days compared with a transition after 14 days in patients with pyogenic vertebral osteomyelitis, thereby evaluating whether a shorter intravenous course can achieve comparable clinical outcomes. Secondary objectives assess a range of additional endpoints, including health-related quality of life measured by patient‑reported outcome instruments, the incidence and causes of treatment failure, differences in hospital length of stay and rates of hospital readmission, comparative tolerability and acceptability of the regimens, the frequency of IV‑related complications, occurrence of Clostridioides difficile-associated diarrhea, variations in functional status and activities of daily living, impact on the ability to work for previously employed patients, differences in patient‑reported experience measures, the need for additional intravenous antibiotic therapy, and overall safety of the treatment strategies.

The trial enrolled adult patients of both sexes, aged 18 years and older, who had a confirmed diagnosis of pyogenic vertebral osteomyelitis based on clinical presentation and characteristic imaging (MRI, PET/CT or PET/MRI) reviewed by the treating physician and an infectious disease specialist. Participants were selected after receiving appropriate intravenous antibiotic therapy for a maximum of seven days and demonstrating a reduction in C‑reactive protein to less than 75 % of the peak value or below 20 mg/L at the time of randomisation. Inclusion required a signed informed consent, an infectious disease treatment recommendation for both intravenous and oral antibiotics, and eligibility for the oral antibiotic list. Both male and female patients meeting these criteria were considered; no specific lifestyle restrictions (e.g., diet or physical activity) were stipulated. The sponsor did not provide information on the total number of participants.

The study is an open‑label, randomized, active‑control, parallel‑group, non‑inferiority trial evaluating an early oral switch strategy in patients with vertebral osteomyelitis. After a screening visit confirming eligibility criteria, participants are randomised to either switch from intravenous to oral antibiotics after 7 days or after 14 days of appropriate intravenous therapy. The trial enrolment period runs from July 2026 to December 2027, and each participant remains in the study for approximately 24 weeks after completion of antibiotic treatment, with scheduled follow‑up visits at week 2, week 6, week 12, and a final end‑of‑study visit at week 24 to assess the composite primary endpoint of clinical failure. Additional visits may be conducted for safety monitoring or if adverse events occur. Early termination of the allocated treatment strategy may occur due to serious adverse events, patient preference, protocol‑defined safety concerns, or other investigator‑determined reasons. The overall trial duration, including recruitment and follow‑up, is designed to capture both efficacy and safety outcomes across the defined study period.

The trial evaluates an early oral antibiotic strategy in patients with Vertebral osteomyelitis, comparing a switch from intravenous to oral therapy after 7 days with a switch after 14 days, both following standard‑of‑care intravenous treatment.

AMOXICLAV BASICS 875 mg/125 mg film‑coated tablets are administered orally at a total dose of 4000 mg per day, divided as appropriate for the study protocol.

CEFALEXIN is given orally at a total daily dose of 4000 mg, administered in the form specified by the study schedule.

CLINDAMYCIN is provided orally with a total daily dose of 1800 mg, to be taken according to the dosing schedule defined in the protocol.

METRONIDAZOLE is taken orally at a total dose of 2000 mg per day, administered as directed by the study regimen.

MOXIFLOXACIN is administered orally with a daily dose of 400 mg, following the prescribed dosing intervals.

PHENOXYMETHYLPENICILLIN is given orally at a total dose of 8 million IU per day, according to the study’s dosing schedule.

CIPROFLOXACIN is provided orally at a total daily dose of 1500 mg, to be taken as specified in the protocol.

RIFAMPICIN is administered orally at a total dose of 1200 mg per day, following the dosing schedule outlined for participants.

Co‑Trimoxazole Forte 160/800 mg tablets are taken orally, delivering a combined dose of 640 mg of sulfamethoxazole/trimethoprim per day.

CEFADROXIL is given orally at a total daily dose of 4000 mg, administered according to the study’s dosing plan.

LEVOFLOXACIN is administered orally with a total dose of 1000 mg per day, following the protocol‑defined schedule.

LINEZOLID is provided orally at a total daily dose of 1200 mg, taken as directed by the trial regimen.

AMOXICILLIN is taken orally at a total dose of 6 g per day, administered according to the study’s dosing instructions.

DOXYCYCLINE is given orally at a total daily dose of 300 mg, following the prescribed dosing frequency.

FLUCLOXACILLIN is administered orally at a total dose of 12 g per day, taken as outlined in the study protocol.

Efficacy will be evaluated primarily by a composite clinical failure endpoint assessed 24 weeks after cessation of antibiotic therapy. The composite includes all‑cause mortality, unplanned spine‑related surgery for vertebral osteomyelitis, relapse of bacteraemia with the primary pathogen, relapse of the initial pathogen cultured from spinal or iliopsoas material, and renewal of intravenous antibiotic therapy for more than 7 days for treatment of vertebral osteomyelitis.

Secondary efficacy assessments comprise patient‑reported and functional outcomes. Health‑related quality of life is measured using the validated Oswestry Disability Index and the EQ‑5D‑5L questionnaires. Functional status and activities of daily living are assessed with the Clinical Frailty Scale (CFS) and the Barthel Index. Additional secondary parameters include duration of hospital stay, occurrence of readmission, early termination of the allocated treatment strategy, complications related to intravenous therapy, incidence of Clostridioides difficile‑associated diarrhoea, ability to work, patient‑reported experience measures, additional intravenous antibiotic therapy exceeding 5 days, and occurrence of severe adverse events related to antibiotic treatment.

All efficacy parameters are collected using the specified validated scales and instruments at baseline and at scheduled follow‑up visits, with the primary composite endpoint evaluated at the 24‑week post‑treatment timepoint. Data are analyzed according to the predefined non‑inferiority criteria, comparing the early switch (after 7 days) with the standard switch (after 14 days) strategy.