RecruitingPhase 4ACTRN12620001088932

The effect of early sedation with dexmedetomidine compared with placebo on 90-day mortality in older critically ill patients

The effect of Early Sedation with Dexmedetomidine vs. Placebo on 90-day mortality in Older Ventilated Critically Ill Patients. A Prospective, Multi-Centre, Double-Blind, Randomized, Controlled Trial

Sponsor

Monash University

Enrollment

3,500 participants

Start Date

Mar 15, 2022

Study Type

Interventional

Conditions

Mechanical Ventilation Sedation

Summary

The proportion of elderly patients presenting to intensive care units following complex surgery or life threatening medical illness requiring mechanical ventilation, cardiovascular and other organ support is rising. More than 180,000 patients are admitted to intensive care units in Australia every year. More than 50% are over the age of 65. The SPICE III study, evaluated the use of early dexmedetomidine (DEX) as primary sedative agent in ventilated critically ill patients compared with usual care. In a pre-specified subgroup analysis, SPICE III found a significant interaction between age and DEX treatment on 90-day mortality with a significant reduction of mortality in mechanically ventilated adults older than the cohort median age of 63.7 yrs. These compelling findings, need to be urgently confirmed because their confirmation will change the practice of sedation in older adults worldwide. Accordingly, we will conduct a complementary multicentre randomised controlled trial in ventilated patients, who are older than 65 years, and expected to remain ventilated for longer than 24 hours. Patients will be randomised to receive DEX infusion started at 1 µg/kg/h or Usual-Care and titrated to target Richmond Agitation Sedation Score of -1 to +1. The primary outcome will be 90-day mortality. A sample size of 3500 will be recruited to detect a 5% reduction in mortality (baseline 37%). Such a cohort will then be merged into a harmonised individual patient based meta-analysis with the 1834 patients of > 63 years of age randomized in the recently completed SPICE III study to provide the most efficient and robust (90% power to detect 4.4% difference) assessment of the effect of dexmedetomidine on mortality in older ventilated adults to date, transform sedation practice, and save thousands of lives in Australia and worldwide.

Eligibility

Sex: Both males and femalesMin Age: 65 Yearss

Inclusion Criteria4

Age is equal to or older than 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 Criteria13

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

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Interventions

Intravenous infusion of dexmedetomidine started shortly after commencement of mechanical ventilation, at a recommended dose of 1 mcg/kg/hr without a loading dose. The infusion will be adjusted between 0 and 1 mcg/kg/hr to achieve target sedation assessed by the Richmond Agitation Sedation Scale (RASS). The default target is RASS score of -1 to+1. The infusion would continue in intensive care until sedation is no longer required or to a max of 28-days whichever comes first. The need for ongoing sedation will be determined by the attending clinician based on frequent clinical assessment. Adherence to the intervention will be monitored by onsite research support staff and the study PI at individual sites. In addition, monitoring through study website via built in queries will be regularly conducted.