PReVENT-NEURO: PRophylaxis against VENTilator-associated infections in NEUROlogically injured ICU patients

Background

Ventilator-associated infections (VAI) represent a significant health burden among ICU patients, particularly those suffering from acute brain injuries. Conditions such as traumatic brain injury, subarachnoid haemorrhage, stroke, and status epilepticus often lead to reduced consciousness and impaired airway reflexes, which increase the risk of aspiration and subsequent lower respiratory tract infections, including pneumonia. These infections can exacerbate brain injury by causing hypoxia and increased intracranial pressure, both of which are linked to higher mortality rates and poor clinical outcomes. Globally, ventilator-associated pneumonia (VAP) is reported to affect between 9% and 27% of intubated patients, with particularly high mortality rates among those with neurological injuries.

In this vulnerable patient group, preventing infections is critical to reducing mortality and long-term disability. However, the use of prophylactic antibiotics remains contentious due to concerns over antibiotic resistance. The SuDDICU trial and other meta-analyses suggest that certain infection control strategies, such as selective decontamination of the digestive tract (SDD) and intravenous antibiotics, can improve survival rates. Given the potential benefits seen in ICU patients with acute brain injuries, there is an urgent need to explore whether intravenous antibiotic prophylaxis, specifically with a narrow-spectrum cephalosporin like ceftriaxone, can reduce 90-day mortality in these patients, while balancing the risks of antimicrobial resistance.

Aims

The primary objective of the PReVENT-NEURO trial is to determine whether administering prophylactic intravenous antibiotics (ceftriaxone) to patients with severe brain injuries on mechanical ventilation reduces 90-day mortality. This intervention targets a critical gap in the management of acute brain injury, where ventilator-associated infections exacerbate the already high mortality and morbidity rates. By comparing ceftriaxone to a placebo, the trial aims to provide conclusive evidence on the efficacy of this treatment in improving survival outcomes.

The impact of this trial is potentially transformative for both patients and healthcare systems. With over 20,000 acute brain injury admissions annually in Australia and New Zealand, and a significant portion of survivors facing lifelong disabilities, reducing infection-related complications could improve functional outcomes and prevent long-term dependence on care. A successful intervention could prevent more than 1,200 deaths annually, provide better quality of life for survivors, reduce healthcare costs through shorter hospital stays and rehabilitation, and enable more patients to return to productive life. This trial addresses an urgent need to improve survival and neurological outcomes in a high-risk ICU population with few existing effective interventions.

Research Methodology

PReVENT-NEURO is a multicentre, double-blind, parallel group, randomised, clinical trial designed to test the hypothesis that among adults with acute brain injuries receiving invasive mechanical ventilation in the ICU (participants), a single dose of 2g ceftriaxone administered as soon as practical following endotracheal intubation (intervention), compared to a matched placebo (comparator), reduces 90-day mortality (primary outcome).

Sites will be selected from our established network that has successfully delivered previous trials at this scale, in Australia and New Zealand.

Current status

Planning and Start-up