Study Synopsis
Title
Early Sedation with Dexmedetomidine vs. Placebo in Older Ventilated Critically Ill Patients: A Prospective, Multi-centre, Double-Blind, Randomized Controlled Trial
Background
The SPICE III trial, in a predefined sub-group analysis, reported that early sedation with DEX was associated with lower mortality in patients older than the median age of 63.7 years.
Objectives
To evaluate mortality and other key clinical outcomes in older patients receiving early sedation with DEX as the primary sedative agent.
Hypothesis
Early sedation with dexmedetomidine as the primary sedative agent reduces 90-day all-cause mortality in ventilated critically ill patients who are ≥ 65 years old.
Design
Prospective, multi-centre, double-blind, placebo-controlled, randomized trial.
Outcomes
- Primary outcome: 90-day all-cause mortality.
- Secondary outcomes:
- Number of days alive and free of coma and delirium at 28 days
- Number of days alive and ventilator free at 28 days
- Major Adverse Kidney Events at 28 days (16) (Mortality + Acute Kidney Injury > stage II, defined by Kidney Disease Improving Global Outcome (KDIGO) definition) (17).
- Duration of mechanical ventilation in survivors
- Hospital length of stay in survivors
- Tertiary and Safety outcomes
- Process related outcomes
- Health economic evaluation
Intervention
Intravenous infusion of dexmedetomidine or blinded matched placebo, starting at a recommended dose of 1 µg/kg/h administered until sedation is no longer required, up to ICU discharge or day 28, whichever occurs first.
Sample size
3500 participants
Population
Patients admitted to a participating intensive care unit, who are ≥ 65 years old, and require mechanical ventilation.
Eligibility criteria
Inclusion criteria:
Must fulfil ALL inclusion criteria
- Age ≥ 65 years
- Intubated and receiving invasive mechanical ventilation in an intensive care unit
- The treating clinicians believe that the patient will remain intubated and ventilated until the day after tomorrow (unlikely to be extubated next day)
- The patient requires immediate ongoing sedative medication for comfort, safety and to facilitate the delivery of life support measures.
Exclusion criteria:
Must have NIL exclusion criteria
- Has been intubated (excluding time spent intubated within an operating theatre or transport) for greater than 12 hours in an intensive care unit
- Proven or suspected acute primary brain lesion such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury
- Proven or suspected spinal cord injury or other pathology that may result in permanent or prolonged weakness
- Admission with a suspected or proven drug overdose or burns.
- Administration of ongoing neuromuscular blockade
- Mean arterial blood (MAP) pressure that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomization
- Heart rate less than 55 beats per minute unless the patient is being treated with a betablocker or a high grade atrio-ventricular block in the absence of a functioning pacemaker
- Known sensitivity to dexmedetomidine
- Acute fulminant hepatic failure
- Receiving full time residential nursing care
- Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment
- Patient has an underlying disease that makes survival to 90 days unlikely
- Previously enrolled in the SPICE IV study
Funding
The SPICE IV is funded by a NHMRC Clinical Trial and Cohort Studies Grant 2019