World Hip Trauma Evaluation - DELPHIC: An external pilot randomised trial of Delirium Prevention in Fragility Hip Fractures with Corticosteroids.

Background Older patients with a hip fracture are at a particularly high risk of developing post-operative delirium due to the injury, pain, analgesia and the surgery required to treat the broken bone.

National audit data in England, Wales and Northern Ireland for 2022 showed that 36% of patients with hip fracture suffered with post-operative delirium.

Post-operative delirium is associated with reduced quality-of-life, longer hospital stays and increased mortality, as well as long-term cognitive impairment.

This proposal seeks to investigate the repurposing of a drug commonly used in the NHS, dexamethasone, to prevent or reduce the severity of post-operative delirium in patients with hip fracture.

Aim The aim of this external pilot trial is to inform the design of a pragmatic multi-centre randomised controlled trial of intravenous dexamethasone vs standard care during hip fracture surgery with regard to severity of delirium symptomatology. Design A multi-centre, parallel-group, randomised, controlled external pilot trial.

Participants All patients aged 60-years and over with a hip fracture are potentially eligible to participate in this trial. Patients who lack capacity may be entered into the trial under a pre-specified consultee agreement process. Patients with contra-indications to intravenous dexamethasone and those treated non-operatively will be excluded.

Intervention Ninety four participants (47 per group) from a minimum of 8 UK hospitals will be randomly allocated to a single injection of 16 mg dexamethasone or standard care (no drug) at the start of anaesthesia and continued during surgery.

All other components of the hip fracture surgery and subsequent care will be at the discretion of the clinical team as per normal clinical practice.

The trial will employ 1:1 random allocation, stratified by centre and the presence or absence of cognitive impairment before surgery.

Outcomes The main outcome for this pilot trial will be to inform the decision as to whether we should move forward into a definitive trial.

We will confirm whether there is signal of a clinically meaningful treatment effect in the proposed definitive trial primary outcome, the recruitment and attrition rates and the fidelity of the intervention delivery. We have defined ambitious and explicit progression criteria using these outcomes.

The primary outcome of a future definitive trial will be the peak Memorial Delirium Assessment Scale over the first five days following surgery, the health-related quality of life score EQ- 5D-5L, development of cognitive impairment, mobility and residential status 4 months after hip fracture diagnosis.

Timelines The trial is expected to start in late 2024, lasting 28 months. Dissemination and impact The results will be reported by scientific paper and conference presentations.

They will be disseminated widely using specialist interest groups – both lay and professional, infographics, podcasts and social media.

We will report data from this external pilot to inform the planning assumptions and delivery of any future definitive trial; we will leverage research infrastructure developed for the pilot trial to reduce cost and accelerate delivery of that definitive trial. Summary results and access to underlying data will be provided to guideline producing bodies such as NICE.