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.
≥ 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
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
Parallel
Ceftriaxone 2g diluted in >200ml 0.9%sodium chloride
Drug2 grams of Ceftriaxone diluted in \>200ml of 0.9%sodium chloride are administered intravenously once following randomisation
Placebo comparator - no ceftriaxone
Drugplacebo: \>200ml 0.9% sodium chloride given as an intravenous infusion once after randomisation
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.
Functional outcome
Functional outcome, as measured using the modified Rankin Scale (mRS) at 180 days after randomisation. A mRS score of 3 to 6 will be categorised as an unfavourable outcome. The mRS ranges from scores 0 to 6. Score of 0 being the best and score of 6 being the worst outcome.
Functional outcome
As measured on the Glasgow Outcome Scale - Extended (GOSE) at 180 days after randomisation. A GOSE score of 1 to 4 will be categorized as an unfavorable outcome The overall GOSE rating ranges from 1 to 8. A rating of 8 being the best and a rate of 1 being the worst.
Ventilator-free days to Day 28
Defined as the number of days free of invasive mechanical ventilation during the first 28 days after randomisation; deaths by day 28 will be assigned negative one ventilator-free days.
Patient reported Health-Related Quality of Life (HRQoL)
Using the EQ-5D-5L, which is an instrument consisting of a descriptive system and a visual analogue scale at 180 days after randomisation. In the descriptive part of the questionnaire, the lower the score (5 to 25) the better the outcome. However, in the digital analogue part of the questionnaire, the higher the score on the scale (1 to 100) the better the health.
Patient reported outcome measure
Measured using the Subarachnoid Haemorrhage Outcome Tool (SAHOT) score at 180 days after randomisation. The tool includes questions regarding general, physical, cognitive and behavioral aspects of life divided into applicability /severity of change.
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