Short or Long Antibiotic Regimes in Orthopaedics (SOLARIO)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Foot; Prosthetic Joint Infection; Osteomyelitis
• Intervention / Treatment: Other: Shorter Systemic Antibiotics; Other: Standard treatment

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.

• Study Type: Interventional
• Enrollment (Actual): 500
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dr. Michelle Kumin; Phone Number: 0300 3047777; Email: maria.dudareva@ouh.nhs.uk
• Study Contact Backup: Name: Maria Dudareva; Phone Number: 07791524686; Email: maria.dudareva@ouh.nhs.uk

Study Locations

• Germany
  • Regensburg, Germany, 93053
    • Universitaetsklinikum Regensburg
• Portugal
  • Porto, Portugal
    • Hospital San Antonio
• Spain
  • Barcelona, Spain, 08003
    • Parc de Salut Mar
• United Kingdom
  • Birmingham, United Kingdom
    • University Hospitals Birmingham
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Teaching Hospitals NHS Foundation Trust
  • Brighton, United Kingdom, BN2 5BE
    • Brighton & Sussex University Hospitals NHS Trust
  • Liverpool, United Kingdom, L7 8XP
    • Royal Liverpool Hospitals
  • London, United Kingdom, W2 1NY
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom, HA1 3UJ
    • London North West Healthcare NHS Trust
  • London, United Kingdom, E1 1FR
    • Barts and the Royal London Hospitals
  • Manchester, United Kingdom, M13 9WL
    • Manchester University NHS Foundation Trust
  • Newcastle, United Kingdom
    • Northumbria Healthcare NHS Foundation Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals Nhs Trust
  • Rotherham, United Kingdom, S60 2UD
    • The Rotherham NHS Foundation Trust
  • Salisbury, United Kingdom, SP2 8BJ
    • Salisbury NHS Foundation Trust
  • Wakefield, United Kingdom, WF1 4DG
    • The Mid Yorkshire Hospitals NHS Trust
  • Dorset
    • Poole, Dorset, United Kingdom, BH15 2JB
      • University Hospitals Dorset
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital
  • Lancashire
    • Wigan, Lancashire, United Kingdom, WN6 9EP
      • Wrightington Hospital
  • London
    • Stanmore, London, United Kingdom, HA7 4LP
      • Royal National Orthopaedic Hospital
  • Oswestry
    • Gobowen, Oswestry, United Kingdom, SY10 7AG
      • The Robert Jones & Agnes Hunt Hospital
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7HE
      • Bone Infection Unit, Nuffield Orthopaedic Centre
  • Wiltshire
    • Swindon, Wiltshire, United Kingdom, SN3 6BB
      • Great Western Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Shorter Systemic Antibiotics; Participants will receive local antibiotic therapy at the time of surgery, followed by one week or less of systemic antibiotic therapy, for bone and joint infection.	Other: Shorter Systemic Antibiotics; Reduced duration of post-operative systemic antibiotic therapy
Active Comparator: Long Systemic Antibiotics; Participants will receive local antibiotic therapy at the time of surgery, followed by four weeks or more of systemic antibiotic therapy (standard treatment recommended by international guidelines), for bone and joint infection.	Other: Standard treatment; Standard duration of systemic antibiotic treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Oxford University Hospitals NHS Trust
• Investigators: Principal Investigator: Matthew Scarborough, Oxford University Hospitals

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2019
• Primary Completion (Estimated): August 7, 2024
• Study Completion (Estimated): August 7, 2024

Study Registration Dates

• First Submitted: January 11, 2019
• First Submitted That Met QC Criteria: January 15, 2019
• First Posted (Actual): January 16, 2019

Study Record Updates

• Last Update Posted (Estimated): October 9, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Infections; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Infectious; Foot Ulcer; Diabetic Foot; Osteomyelitis; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: IRAS No. 244229; PID 13859 (Other Identifier: Oxford University Hospitals NHS Foundation Trust)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No