Clinical trial NCT03806166: Short or Long Antibiotic Regimes in Orthopaedics
Official title: Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): A Randomised Open Label Multi-Centre Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Osteomyelitis
Prosthetic Joint Infection
Diabetic Foot
Lead sponsor: Oxford University Hospitals NHS Trust
Sponsor class: OTHER
First posted: 2019-01-16
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-inferiority randomised controlled trial
Primary purpose: TREATMENT

Brief summary: Research question: If adults with bone or joint infection have local antibiotic therapy, can they do without prolonged treatment with antibiotics by mouth (oral) or injection?

Adults with bone or joint infections are usually given long courses of oral antibiotics or into a vein (intravenous) following surgery. It is also safe to give antibiotics directly into the bone or joint at the time of surgery: this is called local antibiotic therapy. This study investigates whether using local antibiotic therapy would allow shorter courses of oral or intravenous antibiotics, in order to limit antibiotic resistance, side effects and cost.

This study compares short against long courses of oral or intravenous antibiotics for adults who have been given appropriate local antibiotic therapy to treat bone or joint infection. Patients who can take part will be randomly divided into two groups within 7 days of surgery. One group will stop oral or intravenous antibiotics, while the other group will continue for 4 weeks or more (standard treatment).

Adults with bone and joint infections who have already had surgery and local antibiotic therapy will be invited. Patients will not take part if they need intravenous antibiotics for another reason, or if their infection is caused by bacteria resistant to the antibiotic(s) used in their local antibiotic therapy.

Main measurement: how many patients' infections return within 12 months after surgery. This will be decided by a group of doctors who do not know what treatment the patient received.

Other important measurements: serious adverse events; side-effects; quality of life; cost of treatment.

Patients will be asked questions at their usual clinic visits, and will be given a questionnaire at the start of treatment and 1 year later.

Detailed description: Using antibiotics wisely, only when and where they are really needed, is important to prevent superbugs emerging. At the moment, bone and joint infections are usually treated by a combination of surgery and antibiotics. Traditionally, treatment relies on several weeks of antibiotics as tablets or injections (systemic antibiotics), but these can sometimes cause problems.

It is now possible to administer local antibiotics at the time of surgery directly to the site of infection. This allows much higher levels of the antibiotic to be delivered, for days or weeks, following surgery. Therefore, this study will investigate whether local antibiotics with a shorter course of systemic antibiotics can treat bone and joint infections as effectively as local antibiotics with a prolonged course of systemic antibiotics (usual treatment). If so, it may be possible to reduce antibiotic side effects, help to prevent antibiotic resistant bacteria emerging and limit overall treatment costs.

Patients who agree to participate in this study will be allocated at random to two treatment strategies after surgery for bone and joint infection.

One group of patients will be treated with local antibiotics and a long course of systemic antibiotics, which is the usual treatment: this is the 'long group'.

The other group will be treated with local antibiotics and a short course of systemic antibiotics: this is the 'short group' whose treatment differs from the current usual treatment.

Patients will be involved in the study for one year, and infection recurrence will be assessed at the time of routine clinic review up to 12 months after surgery. Whether or not treatment has been successful will be assessed by an independent committee of specialists, who will remain unaware of the patient's allocated treatment strategy.

Eligibility criteria: Inclusion Criteria:

1. Provision of informed consent
2. Aged 18 years or over
3. Presenting with an orthopaedic infection, defined by one or more of the following criteria:

   1. localised pain, OR
   2. localised erythema, OR
   3. temperature ≥ 38.0 C, OR
   4. a discharging sinus or wound
4. Undergoing surgical treatment for the infection
5. Locally administered antibiotic(s) at the site of orthopaedic infection
6. Has received \<= 7 days of systemic antimicrobial therapy after surgery
7. Would ordinarily be managed with a prolonged course (\>= 4 weeks) of systemic antibiotic(s)
8. Specimens for microbiological analysis taken at index surgery

Exclusion Criteria:

Surgical exclusion criteria

1. The index operation was not a definitive procedure with the aim of eradicating infection:

   1. Primary closure has not been achieved, or
   2. Re-look surgery is planned
2. The index operation involved implant retention (e.g. DAIR)

   Microbiological exclusion criteria
3. Any identified micro-organisms from operative specimens from the site of incident infection are fully resistant to the local antibiotic(s) administered at the site of infection

   Medical exclusion criteria
4. Other infection necessitating additional systemic antibiotic treatment beyond 7 days after surgery, such as Staphylococcus aureus bacteraemia, psoas abscess, discitis or bacterial endocarditis
5. If the patient is in a clinical trial involving an Investigational Medicinal Product (IMP) related to infection

Primary outcomes:
measure: Definitive treatment failure (infection recurrence)
timeFrame: 12 months from the time of surgery for bone or joint infection
Secondary outcomes:
measure: Possible or probable treatment failure
timeFrame: 12 months from the time of surgery for bone or joint infection
measure: Serious Adverse Events
timeFrame: 12 months from the time of surgery for bone or joint infection
measure: Antibiotic side effects
timeFrame: This will be assessed at baseline (pre-randomisation, at <7 days of treatment), 6 weeks and 3 months from the time of surgery for bone or joint infection
measure: Quality of life measured by EuroQol 5 Dimensions 5 Levels Score and EuroQol Visual Analogue Score
timeFrame: At baseline and 12 months from the time of surgery for bone or joint infection
Other outcomes:
Locations:
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg
city: Porto
country: Portugal
facility: Hospital San Antonio
city: Barcelona
country: Spain
facility: Parc de Salut Mar
city: Poole
country: United Kingdom
facility: University Hospitals Dorset
state: Dorset
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Wigan
country: United Kingdom
facility: Wrightington Hospital
state: Lancashire
city: Stanmore
country: United Kingdom
facility: Royal National Orthopaedic Hospital
state: London
city: Gobowen
country: United Kingdom
facility: The Robert Jones & Agnes Hunt Hospital
state: Oswestry
city: Oxford
country: United Kingdom
facility: Bone Infection Unit, Nuffield Orthopaedic Centre
state: Oxfordshire
city: Swindon
country: United Kingdom
facility: Great Western Hospital
state: Wiltshire
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Hospitals
city: London
country: United Kingdom
facility: Barts and the Royal London Hospitals
city: London
country: United Kingdom
facility: London North West Healthcare NHS Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Northumbria Healthcare NHS Foundation Trust
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Rotherham
country: United Kingdom
facility: The Rotherham NHS Foundation Trust
city: Salisbury
country: United Kingdom
facility: Salisbury NHS Foundation Trust
city: Wakefield
country: United Kingdom
facility: The Mid Yorkshire Hospitals NHS Trust
Study officials:
affiliation: Oxford University Hospitals
name: Matthew Scarborough
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dudareva M, Kumin M, Vach W, Kaier K, Ferguson J, McNally M, Scarborough M. Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): a randomised controlled open-label non-inferiority trial of duration of systemic antibiotics in adults with orthopaedic infection treated operatively with local antibiotic therapy. Trials. 2019 Dec 9;20(1):693. doi: 10.1186/s13063-019-3832-3.