Title: Duration of INtravenous antibiOtic therapy for Septic Arthritis or acUte osteomyelitis in a paediatRic population – DINOSAUR.
Funder: Department of Health (England)

Abstract: Design/Setting: This feasibility study incorporates an essential service evaluation (which will also produce a robust national consensus guideline pending the outcome of a future RCT) & will combine quantitative methods carried out in 20 tertiary hospitals (est. 4-6 cases/month) & 20 secondary hospitals (est. 1-3 cases/month) across MCRN & CLRN networks with diagnostic & qualitative methods at selected sites.Target population: To assess the potential number of eligible patients all centres will take part in electronic service evaluation of all cases of paediatric OM and SA in a 6 month period with outcomes assessed 3 months after diagnosis. We will collect data regarding conventional & molecular diagnosis (see below) radiological practice length of IV therapy oral switch criteria (fever CRP white cell count) class of antimicrobials used length of total antibiotic therapy clinical outcomes at 3 months.The range of organisms causing paediatric OM/SA will be established in 5 representative centres by aliquots of “routine” microbiological samples being tested using cheap novel targeted PCR (test validated in SE Regional HPA Lab <£5000 total cost for 5 centres/6 months to assess disease phenotype by bacterial cause & class of antimicrobial to use in RCT).Measurement of cost & outcomes: We will use detailed clinician survey and face to face meetings to gain consensus of treatment provider stakeholders (paediatric generalists and infectious diseases clinicians in secondary and tertiary care orthopaedic surgeons paediatric microbiologists paediatric radiologists) on relevant study methodology including current perceived standard of care including radiological tests and laboratory (microbiology CRP white cell count) parameters; treatment regimens; oral switch criteria and of treatment length as a whole; and 3 rounds of Delphi consultation to assess acceptable outcome measures. We will identify possible non-inferiority margins to establish how much higher failure or complication rate is acceptable as a price for reduction in IV therapy length which has significant morbidity (eg line extravasation) and costs (financial and social). Methods to be used & compared will be informed by the findings of the MRC-funded project focussing on methods for specifying the target difference for RCTs (incorporating equivalence margin). Dr J Cook (MRC grant co-PI) has agreed to collaborate.By clinical stakeholder survey we will explore the level of potential engagement with an RCT including questions on i) willingness to act as a recruiting centre and ii) potential treatment regimes to which would be willing to randomise. Qualitative research: We will conduct 30 qualitative interviews with parents & patients to ascertain outcomes important to them their willingness to participate in a trial and their views on the nature and format of information required to provide or withhold informed consent. A topic guide will be prepared interviews will be conducted and (following transcription) data analysed by a trained qualitative researcher. This will enable analysis by case and theme.Health Technologies Being Assessed: IV & oral therapy regimes in paediatric OM/SA.Timetable: The study will last 18 months. After a 2 month lead in service evaluation will take place over 9 months (6 month new case data capture study close 3 months following last entry to database to capture will not identify 3+ month adverse outcomes eg physeal injury which will be evaluated in later RCT). Clinical stakeholder surveys design & qualitative topic guide will be based on service evaluation data so that stakeholder surveys & qualitative interviews will take place in months 12-15 & analysis in months 16-18.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION