Plain English Summary
Background and study aims
A long course of antibiotic therapy given intravenously (i.e., by injection or via a ‘drip’) is the recommended treatment for many serious bacterial infections. It is costly and inconvenient for the patient to remain in hospital for treatment, so outpatient antibiotic therapy (OPAT) programs have been established in many centres to deliver intravenous antibiotics safely and conveniently. Most patients referred to OPAT programs have bone and joint infections. However, there is no clear evidence that bone and joint infections really require long courses of intravenous antibiotics rather than oral antibiotics (tablets). We will compare the outcome of treatment with intravenous and oral antibiotic therapy for patients with bone and joint infection.
Who can participate?
Patients aged 18 or over with an infection in a bone or joint that needs treatment with a long course of antibiotics.
What does the study involve?
The choice of antibiotic is complex, and antibiotics that are suitable oral choices are often not suitable intravenous choices and vice versa. Participants will therefore be randomly allocated to an oral or intravenous ‘strategy’, rather than to individual antibiotics. Patients will be followed up carefully by the study staff for a year; clinical follow up beyond this point may still be required outside the context of the study. We will also look for differences between the two groups in terms of quality of life, side effects, complications, cost and adherence to prescribed antibiotics.
What are the possible benefits and risks of participating?
There are no direct benefits from taking part in the study other than in helping to identify the best treatment strategy for future patients. However, there are advantages and disadvantages of both intravenous and oral antibiotics. Patients allocated to the intravenous group are likely to be closely supervised by specialist nurses. However, many patients find intravenous therapy inconvenient. On the other hand, patients allocated to oral treatment may find the tablets easier and more convenient but they are less likely to be closely supervised by nurses and may therefore be at greater risk of missing doses. At the moment we do not know which antibiotic strategy (intravenous or oral) is most effective, or whether any difference in effectiveness might be balanced by a difference in side effects. If there is a difference, you might be allocated (by chance) to an antibiotic strategy that turns out at the end of the study either to have more side effects or to be less effective. The various antibiotics used to treat bone and joint infections all have different side effects, which the doctor looking after you will explain. In general, antibiotics tablets are more likely to cause nausea and vomiting than antibiotics given by injection. Both tablets and antibiotic injections may cause diarrhoea or a rash. The initial insertion of an intravenous line used for administering antibiotics by injection involves some discomfort but this is usually mild. Intravenous lines have a small risk of becoming infected themselves and very occasionally, they can cause irritation or blood clots in the vein. Under these circumstances, the line may have to be removed. It is important to remember that risks would be no different if you chose not to be in the trial because it is currently standard practice in your hospital to give antibiotics intravenously in the treatment of bone and joint infection.
Where is the study run from?
The Botnar Research Centre, University of Oxford (UK).
When is the study starting and how long is it expected to run for?
From March 2013 to February 2017.
Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK).
Who is the main contact?
Ms Rhea Zambellas
The Botnar Research Centre
University of Oxford
HTA 11/36/29; 13780
Randomised open-label study of oral versus intravenous antibiotic treatment for bone and joint infections requiring prolonged antibiotic treatment: multi-centre study
We will compare the outcome of treatment with intravenous and oral antibiotic therapy for patients with bone and joint infection.
More details can be found at: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=13780
More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/113629
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0003/81156/PRO-11-36-29.pdf
On 02/06/2015 the overall trial end date was changed from 28/02/2016 to 28/02/2017.
Oxford REC B, 08/01/2013, ref: 13/SC/0016
Multi-centre randomised open-label study
Primary study design
Secondary study design
Randomised controlled trial
Patient information sheet
Bone and joint infection
Patients will be randomised to either oral or intravenous antibiotics for the treatment of bone or joint infection
Follow Up Length: 12 month(s)
Primary outcome measures
Treatment failure; Timepoint(s): Recurrence of infection within one year of randomisation
Secondary outcome measures
No secondary outcome measures
Overall trial start date
Overall trial end date
Participant inclusion criteria
1. A clinical syndrome comprising any of the following
1.1. Localized pain OR
1.2. Localized inflammation OR
1.3. Temperature >38.0ºC OR
1.4. A discharging wound AND
2. Willing and able to give informed consent
3. Male and female aged 18 years or above
4. The patient has received 7 days or less of intravenous therapy after an appropriate surgical intervention to treat bone or joint infection (regardless of pre-surgical antibiotics) or, if no surgical intervention is required, the patient has received 7 days or less of intravenous therapy after the start of the relevant clinical episode.
5. Has a life expectancy > 1 year
6. Has a bone and joint infection in one of the following categories
6.1. Native osteomyelitis (i.e., bone infection without metal implants such as artificial joints) affecting limb bone, skull, foot or other site OR 6.2. Native joint infection treated by surgical excision OR
6.3. Prosthetic joint infection treated by debridement and retention of the prosthesis, by one stage exchange of the prosthesis or by excision of the prosthetic joint (with or without planned re-implantation) OR
6.4. Orthopaedic device or bone-graft infection treated by debridement and retention, or by debridement and removal OR
6.5. Spinal infection
Target number of participants
UK Sample Size: 1050
Participant exclusion criteria
1. Staphylococcus aureus bacteraemia (blood stream infection) on presentation or within the last 1 month
2. Bacterial endocarditis (heart valve infection) on presentation or within the last month (NB there are no study mandated investigations. Participants are not required to have echocardiograms, blood cultures, or any other investigations to exclude endocarditis in the absence of a clinical indication)
3. Any other concomitant infection which, in the opinion of the clinician responsible for the patient, required a prolonged intravenous course of antibiotics (e.g. central nervous system infection)
4. Mild osteomyelitis, defined as osteomyelitis which, in the opinion of the clinical investigator, would not usually require a 6 week course of intravenous antibiotics
5. An infection for which there are no suitable antibiotic choices to permit randomization between the two arms of the trial (for instance, where organisms are only sensitive to intravenous antibiotics, which occurred in <5% of patients during recruitment for our pilot study)
6. Previous enrolment in the trial
7. Septic shock or systemic features requiring intravenous antibiotics in the opinion of the treating clinician (the patient may be re-evaluated if these features resolve)
8. The patient is unlikely to comply with trial requirements following randomization (including specific requirement for PO or IV course) in the opinion of the investigator
9. There is laboratory evidence of mycobacterial (e.g. tuberculosis), fungal, parasitic or viral etiology
10. The patient is receiving an investigational medical product as part of another clinical trial.
Recruitment start date
Recruitment end date
Countries of recruitment
Trial participating centre
The Botnar Research Centre,
University of Oxford
Oxford Radcliffe Hospitals NHS Trust (UK)
NIHR Health Technology Assessment Programme - HTA (UK) (ref: 11/36/29)
Funding Body Type
Funding Body Subtype
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
2015 protocol in http://www.ncbi.nlm.nih.gov/pubmed/26690812