Preventing early ventilator infections after severe brain injury

PRophylaxis Against Early VENTilator-associated Infections to Reduce Mortality in Mechanically Ventilated Intensive Care Unit (ICU) Patients With Acute Brain Injuries: a Phase 3 Randomised, Double Blind, Parallel Group, Placebo-controlled Two-side Superiority Trial

This will test whether giving a single dose of the antibiotic ceftriaxone soon after starting mechanical ventilation can prevent lung infections and help adults with severe acute brain injury survive.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 3300 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The George Institute (Academic / other)
• Locations: 9 sites (Kingswood, New South Wales and 8 other locations)
• Trial ID: NCT06819592 on ClinicalTrials.gov

What this trial studies

Adults with recent severe brain injury who require invasive mechanical ventilation are randomly assigned to receive either a single 2 g dose of ceftriaxone or placebo shortly after intubation. The trial compares rates of early ventilator-associated lower respiratory tract infection, death, and functional outcomes between groups. Patients treated at participating ICUs in New South Wales are enrolled within a strict time window (intubation within 12 hours, hospital admission within 72 hours). Standard ICU care is continued for all patients while outcomes are followed for mortality and quality of life measures.

Who should consider this trial

Good fit: Adults (age ≥18) who are invasively mechanically ventilated for an acute severe brain injury (stroke, traumatic brain injury, hypoxic brain injury after cardiac arrest, intracranial haemorrhage, subarachnoid haemorrhage, or cerebral venous sinus thrombosis) and who can receive the intervention within the trial time windows are ideal candidates.

Not a fit: Patients intubated more than 12 hours earlier, admitted more than 72 hours earlier, already on or recently treated with systemic antibiotics, pregnant patients, or those with contraindications to ceftriaxone are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, this approach could lower early ventilator-associated pneumonia rates and improve survival and recovery after severe brain injury.

How similar studies have performed: Prior single-center pilot trials and at least one multicentre randomized trial (including the PROPHY-VAP and a trial after out-of-hospital cardiac arrest) have shown that early prophylactic antibiotics can reduce rates of early ventilator-associated pneumonia.

Eligibility criteria

Inclusion Criteria:

1. ≥ 18 years of age
2. Receiving invasive mechanical ventilation
3. The requirement for mechanical ventilation is because of an acute brain injury due to intracranial haemorrhage, ischaemic stroke, cerebral venous sinus thrombosis, subarachnoid haemorrhage, suspected hypoxic ischaemic encephalopathy post cardiac arrest, or traumatic brain injury.
4. Admitted to an ICU or is anticipated to be admitted to an ICU

Exclusion Criteria:

1. Endotracheal intubation was more than 12 hours ago
2. Hospital admission was more than 72 hours ago
3. Anticipated inability to deliver trial intervention within 90 minutes of randomisation
4. Documented use of antibiotic therapy in the week prior to hospitalisation
5. Currently receiving antibiotic therapy, or intention to prescribe antibiotic therapy, excluding cephazolin for peri-operative prophylaxis
6. Any contraindication to receiving ceftriaxone
7. Known or suspected pregnancy
8. Death within 90 days is deemed inevitable due to the current illness or intercurrent medical conditions
9. Previously enrolled in the PREVENT-NEURO trial.

Where this trial is running

Kingswood, New South Wales and 8 other locations

• Nepean Hospital — Kingswood, New South Wales, Australia (Recruiting)
• St George Hospital — Kogarah, New South Wales, Australia (Recruiting)
• The George Institute — Randwick, New South Wales, Australia (Not_yet_recruiting)
• Royal North Shore Hospital — Sydney, New South Wales, Australia (Recruiting)
• Royal Brisbane and Women's Hospital — Herston, Queensland, Australia (Recruiting)
• Princess Alexandra Hospital — Woolloongabba, Queensland, Australia (Recruiting)
• The Alfred Hospital — Melbourne, Victoria, Australia (Not_yet_recruiting)
• Fiona Stanley Hospital — Perth, Western Australia, Australia (Not_yet_recruiting)
• Wellington Hospital — Wellington, New Zealand (Recruiting)

Study contacts

• Principal investigator: Andrew Udy, Prof — The Alfred
• Study coordinator: Tina Schneider

Conditions All-cause Mortality; Quality of Life; Disability, Intellectual; Neurological Disorder; Acute Brain Injury; Ventilation, Mechanical; Intensive Care Medicine; Mechanical Ventilation