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WHITE Platform Appendix 10 LIT

This study has been designed following a James Lind Alliance Patient and Public Research Priority Setting Partnership, which identified the following question as a top research priority: "What are the best treatments to prevent and treat confusion and delirium after surgery in adults with a broken bone in the leg?".

Summary

Hip fracture is a very 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.Summ

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. For relatives and friends, as well as the patient, delirium is very disturbing. The symptoms of delirium are similar to those of patients with dementia but develop over a short period and tend to vary over time. The great majority of patients suffering with delirium recover quite quickly, but delirium leads to longer hospital stays and a greater risk of complications. Delirium is also associated with an increased risk of developing dementia in later life.

Inflammation, caused by the hip fracture and by the surgery to repair the hip, is thought to be the root cause of delirium. This study will investigate the use of a drug called 'lidocaine' to see if it reduces the risk of delirium after surgery for a 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 falls under the WHITE Platform framework and is open to all patients aged over 60 years with a hip fracture, apart from the very small number of patients who have an allergy or another reason not to have lidocaine. Eligible patients will be approached about the study before their treatment where possible. Patients who are unable to consent for themselves may take part in the trial with the agreement of their relatives or an independent doctor, who will be known as legal representatives.

Patients from at least 12 hospitals in the UK will be approached to take part in the study. 416 participants will take part. Half will be allocated by chance to a slow injection of lidocaine during their surgery, and half to a placebo injection containing no lidocaine. Neither the patients nor their doctors will know which treatment they had to make the study fair. All other elements of the patients' treatment will follow the normal care pathway for all hip fracture patients at the hospital.

We will use a series of simple questions to measure symptoms of delirium in the first five days after surgery. We will also assess the patients' mobility, quality of life and complications and review if they develop symptoms of dementia in the 12 months after surgery. We will also work out the cost of the treatment – for the individual, for the health service and in terms of social support in the year following the fracture. We will also ask people for their permission to monitor their long-term health outcome from national databases that are already being routinely collected. Any information collected from these databases will not contain any details which could identify the patient.

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. 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. UK national audit data for 2018 showed that 25% of all patients with hip fracture suffered with post-operative delirium. 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. People with hip fracture admitted from their own home who develop delirium are twice as likely to die while in hospital, and nearly four times more likely to need placement in a nursing home, compared to those who do not develop delirium in the post-operative period. Furthermore, post-operative delirium is also closely associated with long-term cognitive impairment.

In this trial we will investigate if an infusion of the local anaesthetic lidocaine during surgery, will have an effect on delirium symptoms in the immediate post-operative period and on the development of cognitive impairment, quality of life and mortality in the following year.

Aims and objectives

The primary objective is to quantify differences in peak delirium in the 5 days following hip fracture surgery between the treatment groups.

The secondary objectives are:

  1. To quantify differences in cognitive impairment at 4 and 12 months post-diagnosis of a hip fracture between the treatment groups.
  2. To quantify differences in peak delirium screening in the 5 days following hip fracture surgery between the treatment groups.
  3. To quantify differences in pain in the 5 days following hip fracture surgery between the treatment groups.
  4. To quantify differences in HRQoL at 4 and 12 months post-diagnosis of a hip fracture between the treatment groups.
  5. To quantify differences in mortality within the first 12 months post-diagnosis of a hip fracture between the treatment groups.
  6. To quantify differences in subjective walking performance at 4 and 12 months post-diagnosis between the treatment groups.
  7. To quantify differences in residential status at 4 and 12 months post-diagnosis of a hip fracture between the treatment groups.
  8. To investigate the risk of complications in the first 12 months post-diagnosis of a hip fracture between the treatment groups.
  9. To quantify the differences in costs and comparative cost-effectiveness over the first 12 months post-diagnosis of a hip fracture between the treatment groups.

Study design 

This trial is a double-blinded, pragmatic, multicentre, randomised superiority clinical trial with parallel economic analysis. The primary outcome is the peak MDAS score over the first five days post-surgery. Participants will be allocated using a 1:1 random allocation, stratified by presence / absence of permanent cognitive impairment at presentation and recruitment centre.

This will be a two-phased study. Firstly, an internal pilot will confirm the expected rate of recruitment and optimising of procedures in 4 UK hospitals. Then a definitive phase will extend the randomised comparison to a minimum of 12 UK hospitals.

Site involvement will include screening and recruitment, delirium assessments, baseline forms completion, notes review, query resolution and SAE reporting to one-year post-randomisation. Collection of patient reported-outcomes from patients or proxies from 4 months will be performed by the central research team.

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