PRophylaxis Against Early VENTilator-associated Infections in Acute Brain Injury

NCT06819592 | Recruiting Phase 3 DMC

• 2 other identifiers: TGI-CCP-7738368-63876GNT 2032610.
• Study Type: interventional
• Target: 3,300
• Locations: 2 countries
• Sites: 9

Brief Summary

This research is about whether treatment with a commonly used antibiotic can prevent infections in airway and lungs and improves the chance of surviving, if it is given soon after patients commence mechanical ventilation when they have been admitted to hospital with an acute severe brain injury. An acute severe brain injury can occur as a result of a stroke, a traumatic injury or due to lack of oxygen to the brain that happens as a result of a cardiac arrest. Patients who are unconscious after an acute severe brain injury often need assistance to breath adequately, and this assistance is given by a breathing tube, connected to a mechanical ventilator. This treatment is an emergency medical treatment. The breathing tube is inserted into the patients' airway by either their mouth or neck. For patients who need assistance with their breathing from a mechanical ventilator, infections in the airways and lungs, known as pneumonia, are a common complication. Everyone naturally has bacteria in their mouth, esophagus and stomach. Clinicians think that during the process of inserting the breathing tube, small amounts of these bacteria can be introduced into the airways and lung when people are unconscious following an acute severe brain injury, or during the process of placing the breathing tube into the airways. These bacteria are now in a place they aren't meant to be and can cause an infections in the airways and lungs known as pneumonia. The purpose of this research is to see if giving one dose of a common antibiotic can prevent patients developing pneumonia, which is associated with having a breathing tube inserted and being on a ventilator, improving the chance of recovery following the acute severe brain injury and ultimately improving the chance of surviving. When patients have a known infection, current guidelines are to treat them with antibiotics. Antibiotics work to kill the bacteria causing the infection. When a patient has an infection in their lungs, they often need to stay on the mechanical ventilator for longer. While current practice is to give patients with a proven infection in their airways and lungs (pneumonia) antibiotics, it is unknown if giving an antibiotic to patients to prevent these infections before they show signs of pneumonia may lead to better outcomes.

Conditions

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

Keywords

Acute Brain Injury; Mechanical Ventilation

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  All-cause mortality at day 90 following randomisation. Mortality was chosen as the primary outcome, as it is a patient-important outcome, is not prone to ascertainment bias, and is supported by strong pre-trial data.

  90 days

Secondary Outcomes (1)

• Functional outcome

  Measured 180 days post randomisation

Other Outcomes (16)

• Functional outcome

  Measured 180 days post randomisation

• Ventilator-free days to Day 28

  Measured during first 28 days after randomisation.

• Patient reported Health-Related Quality of Life (HRQoL)

  Measured 180 days post randomisation

Study Arms (2)

Ceftriaxone injection

ACTIVE COMPARATOR

2 grams Ceftriaxone must be diluted in a minimum volume of 200 mL of 0.9% sodium chloride.

Drug: Ceftriaxone 2g diluted in >200ml 0.9%sodium chloride

Placebo

PLACEBO COMPARATOR

In form of a minimum volume of 200 mL of 0.9% sodium chloride.

Drug: Placebo comparator - no ceftriaxone

Interventions

Ceftriaxone 2g diluted in >200ml 0.9%sodium chloride DRUG

2 grams of Ceftriaxone diluted in \>200ml of 0.9%sodium chloride are administered intravenously once following randomisation

Ceftriaxone injection

Placebo comparator - no ceftriaxone DRUG

placebo: \>200ml 0.9% sodium chloride given as an intravenous infusion once after randomisation

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 18 years of age
• Receiving invasive mechanical ventilation
• 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.
• Admitted to an ICU or is anticipated to be admitted to an ICU

You may not qualify if:

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

Sponsors & Collaborators

• The George Institute: lead

Study Sites (9)

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

RECRUITING

St George Hospital

Kogarah, New South Wales, 2217, Australia

RECRUITING

The George Institute

Randwick, New South Wales, 2031, Australia

NOT YET RECRUITING

Royal North Shore Hospital

Sydney, New South Wales, 2000, Australia

RECRUITING

Royal Brisbane and Women's Hospital

Herston, Queensland, 4006, Australia

RECRUITING

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

RECRUITING

The Alfred Hospital

Melbourne, Victoria, Australia

NOT YET RECRUITING

Fiona Stanley Hospital

Perth, Western Australia, 6150, Australia

NOT YET RECRUITING

Wellington Hospital

Wellington, New Zealand

RECRUITING

MeSH Terms

Conditions

Intellectual Disability; Nervous System Diseases; Brain Injuries; Respiratory Aspiration

Interventions

Ceftriaxone; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes

Intervention Hierarchy (Ancestors)

Cefotaxime; Cephacetrile; Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Anthony Delaney, Prof

  The George Institute

  STUDY CHAIR

• Andrew Udy, Prof

  The Alfred

  PRINCIPAL INVESTIGATOR

• Edward Litton, Prof

  Fiona Stanley Hospital

  PRINCIPAL INVESTIGATOR

• Paul Young, Prof

  Wellington Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tina Schneider

CONTACT

+61 02 8052 4562; tschneider@georgeinstitute.org.au

Dorrilyn Rajbhandari

CONTACT

+61 02 8052 4301; drajbhandari@georgeinstitute.org.au

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study staff will be blinded to the study intervention except the unblinded study staff who are undertaking randomisation and study unblinded drug preparation and delivery of Blinded study drug to bedside staff only. These designated unblinded staff are not involved in direct patient care of the participant or aprt of the research team.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre, phase 3, randomised, double blind, parallel group, placebo-controlled two-side superiority trial.

Study Record Dates

• First Submitted: January 2, 2025
• First Posted: February 11, 2025
• Study Start: October 30, 2025
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 19, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

AU (8); NZ (1)