This project is suitable for DPhil. Central to the project is a multi-centre randomised controlled trial involving patients with bone and joint infection, management of which usually consists of a combination of careful, complete surgical debridement and the use of a prolonged (>4 weeks) course of systemic antibiotic therapy. Increasingly, antibiotics are being used locally at the site of infection with good observational results but with very limited trial evidence to support their routine adoption in clinical practice and few data to to allow comparison of their efficacy against systemic therapy. This trial therefore seeks to establish whether the use of local antibiotic therapy in a biocompsite carrier, implanted at the time of surgery, is non-inferior to the current standard of care.
We plan to recruit 500 participants from nine centres specialising in the management of orthopaedic infection. Eligible participants will have local antibiotic therapy implanted at the time of surgery. Provided that microbiology results do not show resistance to the local antibiotic used, participants will be randomised post-operatively to either stop systemic therapy within seven days of surgery or to continue with systemic therapy as standard of care for four weeks or more.
The primary outcome will be treatment failure within one year of surgery. The secondary outcomes will include possible or probable treatment failure, serious adverse events, antibiotic related side effects, resource use, patient reported outcome measures and protocol deviations.
If the trial demonstrates non-inferiority of local therapy, it may limit the incidence of adverse drug reactions, treatment complications and emergence of antibiotic resistance that are commonly associated with systemic therapy. In addition, it is likely to facilitate greater convenience for patients and may reduce overall cost of therapy.
The project will have three supervisors: Martin McNally (consultant orthopaedic surgeon) and Matthew Scarborough (consultant in clinical infection) will be responsible for supervision of the clinical aspects of the trial. Prof Brian Angus (professor of infectious diseases) will provide academic supervision and oversight.
Details of the research group
The Oxford Bone Infection Unit has an extensive research history under the auspices of the Nuffield Department of Medicine (NDM) and Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science (NDORMS) for specific projects. It hosts an annual international conference dedicated to the multidisciplinary management of bone and joint infection (http://obic.org.uk/biu/). Due to the increasing activity in clinical trials, the BIU has now developed a research hub staffed by a post-doctoral scientist experienced in trial management and research coordination, an administrator, two research nurses, an infectious diseases/microbiology specialist and two orthopaedic surgeons specialising in musculoskeletal infection. We currently supervise two PhD students and one master’s student but there is a close affiliation with a large research group led by Prof Derrek Crook in the Experimental Division of the Nuffield Dept of Medicine (https://www.expmedndm.ox.ac.uk/infectious-diseases-microbiology). Similarly, the Bone Infection Unit has close ties to the Botnar Research Centre which plays host to the University of Oxford's Institute of Musculoskeletal Sciences (https://www.ndorms.ox.ac.uk/about/botnar-research-centre).
Details on specific training opportunities relevant to the project
The Botnar Research Centre plays host to the University of Oxford's Institute of Musculoskeletal Sciences, which enables and encourages research and education into the causes of musculoskeletal disease and their treatment.
Training will be provided in data management, clinical trial design and methodology, medical statistics and health economic evaluation. A core curriculum of lectures will be taken in the first term to provide a solid foundation in a broad range of subjects including musculoskeletal biology, inflammation, epigenetics, translational immunology, data analysis and the microbiome.
Students will attend regular seminars within the department and those relevant in the wider University. Students will be expected to present data regularly in the departmental PGR seminars, the Oxford Bone Infection Research Group and to attend external conferences to present their research globally. Students will also have the opportunity to work closely with the Experimental Division of the Nuffield Department of Medicine and the BRC Infection Theme led by Derrek Crook.
Students will have access to various courses run by the Medical Sciences Division Skills Training Team and other departments. All students are required to attend a 2 - day Statistical and Experimental Design course at NDORMS.
International collaboration with a leading statistician and health economist will form part of the project.
As the trial involves recruitment of patients, applicants must have a clinical qualification and relevant training in clinical infection to the level of specialist registrar (ST3). The project affords extensive experience and training in the clinical management on musculoskeletal infection and the successful applicant will have to opportunity to join the medical, surgical and allied health teams on the Bone Infection Unit and in the clinic.
How to Apply
The department accepts applications throughout the year but it is recommended that, in the first instance, you contact the relevant supervisors or the Graduate Studies Officer, Sam Burnell ([Email Address Removed]), who will be able to advise you of the essential requirements. Interested applicants should have or expect to obtain a first or upper second class BSc degree or equivalent, and will also need to provide evidence of English language competence. The application guide and form is found online (https://www.ox.ac.uk/admissions/graduate/applying-to-oxford/application-guide?wssl=1) and the DPhil or MSc by research will commence in October 2019. For further information, please visit http://www.ox.ac.uk/admissions/graduate/applying-to-oxford.
M. A. McNally et al. Single-stage treatment of chronic osteomyelitis with a new absorbable, gentamicin-loaded, calcium sulphate/ hydroxyapatite biocomposite. Bone Joint J 2016;98-B:1289–96.
J. Y. Ferguson et al. The use of a biodegradable antibiotic-loaded calcium sulphate carrier containing tobramycin for the treatment of chronic osteomyelitis. Bone Joint J 2014; 96-B:829–36
I. Byren et al. One hundred and twelve infected arthroplasties treated with ‘DAIR’ (debridement, antibiotics and implant retention): antibiotic duration and outcome. Journal of Antimicrobial Chemotherapy 2009; 63, 1264 – 1271