Short or Long Antibiotic Regimes in Orthopaedics

Diabetic Foot Clinical Trial

— SOLARIO  

Official title:

Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO): A Randomised Open Label Multi-Centre Clinical Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03806166
• Other study ID #: IRAS No. 244229
• Secondary ID: PID 13859
• Status: Active, not recruiting
• Phase: N/A
• Start date: February 21, 2019
• Est. completion date: August 7, 2024

Study information

• Verified date: October 2023
• Source: Oxford University Hospitals NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 500
• Est. completion date: August 7, 2024
• Est. primary completion date: August 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetic Foot
• Osteomyelitis
• Prosthetic Joint Infection

Intervention

Other:
• Shorter Systemic Antibiotics
Reduced duration of post-operative systemic antibiotic therapy
• Standard treatment
Standard duration of systemic antibiotic treatment

Locations

Country	Name	City	State
Germany	Universitaetsklinikum Regensburg	Regensburg
Portugal	Hospital San Antonio	Porto
Spain	Parc de Salut Mar	Barcelona
United Kingdom	University Hospitals Birmingham	Birmingham
United Kingdom	Blackpool Teaching Hospitals NHS Foundation Trust	Blackpool
United Kingdom	Brighton & Sussex University Hospitals NHS Trust	Brighton
United Kingdom	The Robert Jones & Agnes Hunt Hospital	Gobowen	Oswestry
United Kingdom	Royal Liverpool Hospitals	Liverpool
United Kingdom	Barts and the Royal London Hospitals	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	London North West Healthcare NHS Trust	London
United Kingdom	Manchester University NHS Foundation Trust	Manchester
United Kingdom	Northumbria Healthcare NHS Foundation Trust	Newcastle
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Bone Infection Unit, Nuffield Orthopaedic Centre	Oxford	Oxfordshire
United Kingdom	University Hospitals Dorset	Poole	Dorset
United Kingdom	The Rotherham NHS Foundation Trust	Rotherham
United Kingdom	Salisbury NHS Foundation Trust	Salisbury
United Kingdom	Southampton General Hospital	Southampton	Hampshire
United Kingdom	Royal National Orthopaedic Hospital	Stanmore	London
United Kingdom	Great Western Hospital	Swindon	Wiltshire
United Kingdom	The Mid Yorkshire Hospitals NHS Trust	Wakefield
United Kingdom	Wrightington Hospital	Wigan	Lancashire

Sponsors (1)

Lead Sponsor	Collaborator
Oxford University Hospitals NHS Trust

Countries where clinical trial is conducted

Germany,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Definitive treatment failure (infection recurrence)	Proportion of participants in each treatment group experiencing definitive treatment failure (infection recurrence), ascertained by an independent committee of experts unaware of the treatment allocation of the participant, according to established criteria.	12 months from the time of surgery for bone or joint infection
Secondary	Possible or probable treatment failure	Proportion of participants in each treatment group experiencing clinical features suggesting possible or probable infection recurrence, not meeting the definition for definitive treatment failure, determined by an independent committee of experts unaware of treatment allocation, where microbiological culture is not done or is negative. Ascertainment is based on established clinical criteria associated with, but not diagnostic of, orthopaedic infection.	12 months from the time of surgery for bone or joint infection
Secondary	Serious Adverse Events	Proportion of participants in each treatment group experiencing Serious Adverse Events including mortality	12 months from the time of surgery for bone or joint infection
Secondary	Antibiotic side effects	Proportion of participants in each treatment group experiencing possible side-effects from systemic antibiotic treatment, adjusted for severity on a 3-point scale	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
Secondary	Quality of life measured by EuroQol 5 Dimensions 5 Levels Score and EuroQol Visual Analogue Score	EQ-5D-5L score distribution across 5 dimensions (mobility, self-care, ability to complete usual activities, pain or discomfort, anxiety or depression) for participants, ranging from 1 (worst) to 5 (best) for each dimension. EQ-VAS score distribution for participants, for self-reported health state, ranging from 0 (worst) to 100 (best).	At baseline and 12 months from the time of surgery for bone or joint infection