WHiTE-13 DECI

This study has been designed following a James Lind Alliance Patient and Public Research Priority Setting Partnership, which identified the following question as a key 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?”

A broken hip (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 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’ around the time of 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. In the short-term, delirium leads to longer stays in hospital and an increased risk of complications including death. In the longer-term, delirium is closely linked with an increased risk of developing dementia. Delirium is thought to be caused by inflammation in the brain. The inflammation is triggered by the injury and thought to get worse during surgery. This study will investigate a drug called infliximab which is an anti-inflammatory drug. The aim of this study is to decide if patients who have operations on broken hips are less likely to have delirium, if we treat them with infliximab during the operation.

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 anti-TNF agent infliximab during surgery, has 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.

Primary objective

The primary objective is to compare peak delirium in the 5 days following hip fracture surgery between the treatment groups using the Memorial Delirium Assessment Scale (MDAS).

Secondary objectives

1. To compare cognitive impairment scores at 4- and 12-months post-diagnosis of a hip fracture between the treatment groups using the Telephone Interview for Cognitive Status (TICS) questionnaire.

2. To compare health-related quality of life at 4- and 12-months post-diagnosis of a hip fracture between the treatment groups.

3. To compare mortality risk within the first 12 months post-diagnosis of a hip fracture between the treatment groups.

4. To compare mobility at 4- and 12-months post-diagnosis between the treatment groups.

5. To compare residential status at 4- and 12-months post-diagnosis of a hip fracture between the treatment groups.

6. To compare the risk and pattern of complications at any point within the first 12 months post-diagnosis of a hip fracture between the treatment groups.

Study design

This study is open to all patients aged over 60 years with a hip fracture, apart from the very small number of patients who do not have an operation on their hip. Eligible patients will be approached for recruitment 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. Patients at approximately 8 hospitals in the UK will be approached to take part in the study. 416 participants will take part, with half being allocated by chance to receiving infliximab, and half to receiving a placebo containing no infliximab. 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.