Title: Oral Versus Intravenous Antibiotics (OVIVA) for Bone and Joint Infection
Funder: Department of Health (England)

Abstract: DESIGN: A multi-centre randomized controlled trial to determine non-inferiority of strategies of 6 weeks oral versus intravenous antibiotics for bone and joint infection. The trial will be open and pragmatic (randomized to strategy rather than individual antibiotics) because the treating clinician needs to select specific antibiotics according to the patient’s condition and bacterial antibiotic susceptibility tests.Design feasibility has been tested in a pilot phase in Oxford: 200+ patients were recruited over 2 years ~20 primary endpoints identified and only 2 patients were lost to follow up. No patient was withdrawn from their allocated strategy without meeting criteria pre-specified in the protocol.SETTING: We will recruit patients with bone and joint infection during their inpatient stay in; Oxford University Hospitals Royal Liverpool University Hospital Royal United Hospital Bath Bristol Royal Infirmary Birmingham Heartlands Hospital Royal Free Hampstead Hospital Guys and St Thomas’ Hospitals Hull Royal Infirmary Royal Edinburgh Hospital Gartnavel General Hospital in Glasgow University of Wales Hospital Sheffield Teaching Hospitals Leeds Teaching Hospitals and Ninewells Hospital in Dundee.TARGET POPULATION: Participants will be over 18 give informed consent and have a clinical diagnosis of infection in one of the following categories; native osteomyelitis (in any anatomical location) prosthetic joint associated infection orthopaedic device associated infection discitis/ spinal osteomyelitis/ epidural abscess - and would have ordinarily been treated with prolonged (i.e. at least 6 weeks) of intravenous antibiotics by the local clinician. Participants may still need continued oral antibiotics after their initial randomized therapy (e.g. patients with retained metalwork). Participants should have completed <1 week of intravenous antibiotics at randomization. Patients with endocarditis or Staphylcoccus aureus bacteraemia will be excluded. Each patient can only be randomised once in the trial.We will divide the recruited participants into subgroups of “definitive” infection (supported by objective findings) and “probable” or “possible” infection. An endpoint committee will adjudicate probable” or “possible where objective criteria are not met.HEALTH TECHNOLOGIES BEING ASSESSED: 6 weeks of oral versus intravenous antibiotic therapy leaving the choice of agent to the clinician. Participants will be randomized during the first week after starting antibiotics for this infection so participants randomized to oral therapy may have received up to 7 days of intravenous therapy before switching. Participants in the intravenous therapy group may receive additional adjunctive oral antibiotics such as rifampicin if required. Prolonged intravenous treatment is the current standard practice delivered by an out-patient antibiotic treatment (OPAT) programme. The most commonly used intravenous agents are ceftriaxone teicoplanin or ertapenem costing £20-£70 per day plus the cost of nursing time to deliver them. The typical oral agents used will be ciprofloxacin rifampicin clindamycin or doxycycline costing 20 pence to £6 per day for which daily supervision or patient training are not required.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;6.1 PHARMACEUTICALS
Health categories: INFECTION