Title: Management of Infected Knee Replacements-Obtaining Best Evidence-MIKROBEA feasibility study for a randomised controlled trial of one-stage or two-stage surgery for prosthetic knee infection
Funder: Department of Health and Social Care

Abstract: Research Question: Is it feasible to carry out a multicentre randomised controlled trial assessing clinical and cost-effectiveness of one-stage versus two-stage revision surgery for prosthetic knee infection? Background: 1.4% of patients with primary knee replacement develop a deep bacterial infection within 2 years of surgery. In 2017, there were 1503 revision knee replacement operations in the UK for prosthetic joint infection. Patients face complex and protracted treatments imposing heavy physical, social, and psychological burdens upon them. Most patients are managed with two stage surgical revision (implant removal, weeks of antibiotics, prosthesis re-implantation). 20% have a one operation with immediate implant exchange. When comparing the two techniques, the literature does not: Demonstrate differences in infection eradication rates. Support a specific strategy. The need for a randomised trial assessing whether a one-stage strategy is acceptable/effective compared to the two-stage strategy is widely recognised. Firstly, a study is needed to ensure feasibility/ acceptability of this to patients and surgeons. Aim: Assess feasibility of conducting a randomised controlled trial evaluating the clinical- and cost-effectiveness of one versus two-stage revision surgery for prosthetic knee infection. Objectives: 1. Evaluate number of eligible patients, analysing reasons for non-participation over 20 months. 2. Assess: Feasibility and experience of process of study explanation (recruitment/randomisation) between patients and surgeons Study attrition rate Completion and findings of pre- and 6 month post-operative Patient Recorded Outcome Measures Differences in study recruitment/ attrition rates between study sites Feasibility of collecting health resource use and EQ-5D-5L data Estimate of cost of study arms Out-of-pocket cost/ income loss in study arms Methodology: Design: feasibility study using a randomised controlled trial design and mixed research methods. Setting: 2 NHS centres: Exeter and Oxford Study population: patients with prosthetic joint infection requiring revision knee replacement Intervention: 1 versus 2 stage surgery for treatment of prosthetic joint infection Measurement of outcomes: Primary: Assess recruitment rate: recruits compared to potential participants over 20 months. Secondary: Assess: 1. Process of study explanation between patients and surgeons using qualitative analysis of pre-operative recorded discussions about study participation 2. Patient's post-operative experience/acceptability of surgery and study through qualitative analysis of data from semi-structured telephone interview 3. Surgeon post-operative experience/acceptance of study via semi-structured interview 4. Surgeon reflection of study involvement via personal interview with qualitative researcher 5. Reasons for non-participation via telephone call to non-participants 6. PROMS data and completion rates before and 6 months after surgery ensuring safety to proceed 7. Health resource use and EQ-5D-5L data collection rates 8. Out-of-pocket cost/ income loss in both arms 9. Recruitment/retention comparison between recruitment sites Sample Size: 40 patients (20 per arm) allowing 25% attrition rate leaving 30 patients (15 per arm) Timeline for delivery: Study duration 30 months: Recruitment 20 months Further 6 months follow up, 3 months analysis and 1 month dissemination. Anticipated impact: Findings will be disseminated to researchers, healthcare professionals and the public and used to inform a NIHR HTA grant application for a future study comparing one versus two stage revision knee surgery for prosthetic joint infection.

Lay abstract: Total knee replacement (TKR) surgery is common, with over 100,000 operations performed in the United Kingdom in 2015. After surgery, about 1% patients develop a deep infection in their replaced knee, called a prosthetic joint infection (PJI). Untreated PJI can cause severe pain, disability and death. Two types of operations can be performed to treat PJI. A one-stage revision operation involves one operation to remove the joint, cleaning the infected area and implant a new joint immediately. A two-stage revision operation involves two operations: the joint is removed in one operation and a temporary cement &quot;spacer&quot; inserted. The infection is treated with antibiotics for several months, and then a new joint is implanted in a second operation. Both treatments are widely used and are good at treating infection but we don t know which has the best long-term outcomes for patients. There are pro's and cons to both. In the future we would like to run a project to find out whether it is better for patients to have one-stage or two-stage revision surgery. Before running the larger future project, we are doing this small study: To evaluate if patients and surgeons will take part in this type of project and that it is acceptable to them To establish the optimal way of running the future larger study To establish the best way of explaining the study to potential participants To identify potential barriers to study recruitment in the anticipation we will to identify strategies to overcome them. The study will take place in 2 high volume revision TKR centres- Exeter and Oxford. We expect to recruit 40 patients. Half will be randomly chosen to receive the one-stage and half the two-stage revision operation. We will record the pre-operative consultations between patient and surgeon and analyse the recordings to identify best practice in explaining the study and to highlight any problems when recruiting. We will also talk to surgeons and patients separately after surgery about: Their thoughts on this project Their experiences of being involved in the research The experience of undergoing revision TKR surgery. These 3 topics will help to further inform our understanding of treatment and care and identify any potential differences between the two surgical strategies that may need to be addressed prior to a larger trial evaluating whether a one-stage or two-stage revision operation is better for patients. We have discussed this project with our patients research panel who have had input in to the study design, consent form and patient information leaflet. Two members will sit on the Trial Management Group. We aim to publish and present our findings at scientific orthopaedic meetings and use the findings to optimise the design of the future larger study.

Research activity codes: 6.4 SURGERY;7.3 MANAGEMENT AND DECISION MAKING
Health categories: INFECTION;MUSCULOSKELETAL