Bone Infection, Joint Infection
Conditions
Keywords
oral, intravenous, antibiotics, bone, joint, infection
Brief summary
The study will compare the outcomes of treating bone and joint infections with 6 weeks of intravenous antibiotics with 6 weeks of oral antibiotic treatment. The trial is of antibiotic strategy rather than of individual antibiotics. The study will be open label, but the primary outcome will be proven failure of infection treatment, determined by pre-established objective criteria for treatment failure. The null hypothesis tested is that there will be no difference in treatment failure rates.
Detailed description
A long course of antibiotic therapy given by a drip (i.e. intravenous) is recommended treatment for many serious bacterial infections. It is costly and inconvenient for the patient to remain hospitalised for therapy, so outpatient antibiotic therapy (OPAT) programmes have been established in many countries to deliver intravenous antibiotics safely and conveniently. The majority of patients referred to OPAT programmes have bone and joint infections. However, there is no clear evidence that bone and joint infection really require long courses of intravenous antibiotics rather than oral antibiotics. We will compare the outcome of treatment with intravenous versus oral antibiotic therapy for patients with bone and joint infection. The choice of antibiotic is complex, and antibiotics that are suitable oral choices are often not suitable intravenous choices and vice versa. Subjects will therefore be randomized to an oral or intravenous strategy, rather than to individual antibiotics. Outcomes will be determined by pre-established objective criteria for treatment failure. We have conducted a pilot study in one centre (Oxford), recruiting approximately 200 patients, and are now expanding to include multi-centre recruitment in the UK, aiming to recruit 1050 patients.
Interventions
DRUGAntibiotics
The trial protocol does not specify individual antibiotics, as the trial question is one of strategy (i.e. oral vs intravenous route) rather than individual antibiotics. Within allocated strategy (i.e. oral or intravenous) antibiotics will be selected by a clinician with reference to the subject's clinical condition, microbiological data and local guidelines.
Sponsors
Oxford University Hospitals NHS Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Is willing and able to give informed consent for participation in the study. Has a bone and joint infection one of the following categories; 1. Native osteomyelitis. 2. Native joint septic arthritis. 3. Diabetic foot infection with osteomyelitis. 4. Prosthetic joint associated infection. 5. Discitis/ spinal osteomyelitis/ epidural abscess * Has had at least 48 hours, but not more than 7 days, of IV antibiotic therapy already given after definitive surgical management. * Has a clinical diagnosis of bacterial infection (caused by any organism excepting mycobacteria). * Is clinically stable in the opinion of the study clinicians, has no further interventions to treat acute infection required or planned.
Exclusion criteria
* Has Staph aureus bacteraemia. * Has suspected bacterial endocarditis. * Has suspected mediastinal infection. * Has suspected central nervous system infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Frequency of Definite Failure of Infection Treatment. | 1 year | Number of participants with definite failure of infection treatment defined by microbiological, histological and clinical criteria and assessed by an independent blinded endpoint committee |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Oral Antibiotics Antibiotics: The trial protocol does not specify individual antibiotics, as the trial question is one of strategy (i.e. oral vs intravenous route) rather than individual antibiotics.
Within allocated strategy (i.e. oral or intravenous) antibiotics will be selected by a clinician with reference to the subject's clinical condition, microbiological data and local guidelines. | 527 |
| Intravenous Antibiotics Antibiotics: The trial protocol does not specify individual antibiotics, as the trial question is one of strategy (i.e. oral vs intravenous route) rather than individual antibiotics.
Within allocated strategy (i.e. oral or intravenous) antibiotics will be selected by a clinician with reference to the subject's clinical condition, microbiological data and local guidelines. | 527 |
| Total | 1,054 |
Baseline characteristics
| Characteristic | Intravenous Antibiotics | Total | Oral Antibiotics |
|---|---|---|---|
| Age, Customized | 61 years | 60 years | 60 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United Kingdom | 527 participants | 1054 participants | 527 participants |
| Sex: Female, Male Female | 207 Participants | 376 Participants | 169 Participants |
| Sex: Female, Male Male | 320 Participants | 678 Participants | 358 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 527 | 17 / 527 |
| other Total, other adverse events | 80 / 527 | 86 / 527 |
| serious Total, serious adverse events | 138 / 527 | 146 / 527 |
Outcome results
Primary
The Frequency of Definite Failure of Infection Treatment.
Number of participants with definite failure of infection treatment defined by microbiological, histological and clinical criteria and assessed by an independent blinded endpoint committee
Time frame: 1 year
Population: Modified ITT (excluding participants without available endpoint data)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Oral Antibiotics | The Frequency of Definite Failure of Infection Treatment. | 67 Participants |
| Intravenous Antibiotics | The Frequency of Definite Failure of Infection Treatment. | 74 Participants |