Title: WHiTE-LIT– World Hip Trauma Evaluation - Lidocaine Intravenous Trial: a feasibility study for a randomised controlled trial of the effect of intravenous lidocaine at the time of surgery on outcomes following hip fracture
Funder: Department of Health and Social Care

Abstract: Research question Does intravenous lidocaine result in a clinically relevant reduction in delirium in the first five days after hip fracture surgery in older people? Background Delirium is a common neuropsychiatric syndrome defined as disturbance of attention, awareness and cognition which develops over a short period of time, represents a change from baseline and tends to fluctuate during the course of the day. It is often seen after surgical interventions in older patients. As well as being distressing for patients and their families, post-operative delirium is associated with poor functional outcomes, reduced quality of life, longer hospital stays and increased mortality. Older patients with hip fracture are at particularly high risk of developing post-operative delirium due to the physiological stress and inflammation from the injury, pain and associated analgesia, and the surgery required to treat the broken bone. There is good evidence that inflammation is a potential target for prevention of delirium. Intravenous lidocaine has clinically relevant anti-inflammatory properties and has been widely and safely used in other surgical fields to improve early postoperative recovery. It is therefore an attractive candidate therapy for reducing delirium in people with hip fracture. Aims and Objectives The aim of this feasibility study is to inform the design of a pragmatic multi-centre randomised controlled trial of intravenous lidocaine vs placebo during hip fracture surgery on severity of delirium symptomatology. Feasibility objectives: 1) To establish the rate of recruitment in the context of a multi-centre feasibility pragmatic trial. 2) To optimise trial processes including intervention delivery and data collection. Definitive trial objective: To quantify differences in peak delirium in the 5 days following hip fracture surgery between the trial intervention groups. Methods A randomised, placebo controlled, double-blinded, multicentre trial of intravenous lidocaine given during anaesthesia and surgery for hip fracture. Participants and setting: The study will randomise 120 participants on a 1:1 basis across at least 4 recruitment centres. Main inclusion / exclusion criteria: hip fracture, aged >60 years / contraindications to use of lidocaine. People without capacity to consent for themselves will be included in the study subject to ethical and regulatory approvals. Intervention: intravenous lidocaine 1.5mg/kg bolus and 1.5mg/kg/h infusion; placebo: 0.9% saline. Feasibility outcomes: trial recruitment rate, optimisation of trial processes. Clinical outcomes: Primary &ndash; peak postoperative delirium assessed in first five days using the Memorial Delirium Assessment Scale. Secondary: days 1-5: functional pain assessment; 4 months: Cognitive assessment, health-related quality of life, mobility, mortality. Timelines for delivery Start March 2021; Completion Jan 2023 Anticipated Impact and Dissemination Primary impact of feasibility will be progression to definitive study. Main study impact: change in clinical practice (if beneficial), incorporation in NICE guidance, and national and international specialty guidance. Dissemination will be coproduced with PPI group: publications, reports, slide-decks and national and international presentations. PPI co-applicant will lead some dissemination activity. Introduction into clinical practice would lead to reduction in short and potentially long-term morbidity with likely associated health economic benefits.

Lay abstract: Hip fracture is a serious injury that requires surgery to repair or replace the broken bone followed by a long period in hospital to recover. Around a quarter of patients with hip fracture die within a year and those that survive have a permanent loss of their quality of life. Worldwide there are 1.3 million hip fractures each year, with more than 70,000 in the UK. Around a quarter of patients who have a hip fracture have an episode of delirium after their surgery. Delirium is a condition where the patient loses awareness of themselves and their environment, and has difficulty thinking clearly. Delirium is very disturbing and although most people with delirium recover quite quickly, it leads to longer hospital stays, greater risk of complications and developing dementia in later life. Inflammation, caused by the hip fracture and by surgery, is thought to be the root cause of delirium. This study will investigate a drug called lidocaine to see if it reduces the risk of delirium after surgery for hip fracture. Lidocaine is already used very widely in the NHS as a local anaesthetic, but it also has a strong anti-inflammatory effect. If lidocaine is given to a patient during surgery to reduce inflammation, it may reduce the severity of delirium after surgery. This study is a feasibility study - a smaller version of the main study to make sure it will work efficiently. Patients from at least 4 hospitals in the UK will be approached to take part in the study. 120 participants aged over 60 years with a hip fracture will take part. Patients who are unable to consent for themselves may take part in the trial with the agreement of their relatives or an independent doctor. Half will be allocated by chance to an injection of lidocaine during their surgery, and half to a sham injection containing salty water. Neither the patients nor their doctors will know which treatment they had to make the study fair. All other elements of treatment will follow the normal care pathway for hip fracture patients at the hospital. We will ask simple questions about symptoms of delirium in the first five days after surgery. We will also assess participants mobility, quality of life and complications and review if they develop symptoms of dementia in the 4 months after surgery. The trial will start in March 2021 and finish in Jan 2023. Following this we hope to secure funding for the main study involving around 400 patients. The results will be presented at scientific meetings and published in medical journals. Patient representatives will produce a lay summary and take the results to patient advocacy groups and share them through social media.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INJURIES AND ACCIDENTS