Trial Summary

Background

The use of sedative drugs in intensive care is widespread. There is growing evidence that the centrally mediated alpha-2 agonist sedative dexmedetomidine facilitates rousable sedation, shortens ventilation time, and diminishes the occurrence of delirium. Whether these advantages are associated with improvement in patient-centered outcomes, such as long-term mortality and cognitive function, is not known.

Aim

The primary aim of this study is to determine whether Early Goal-Directed Sedation, compared to standard care sedation, reduces 90-day mortality in critically ill patients who are expected to require mechanical ventilation for longer than 24 hours.

Design

Prospective, un-blinded, randomised, controlled phase III trial.

Patient Population

Intensive care patients who require ventilation and sedation

Sample Size

4000

Methods

Eligible patients will be randomised early after intubation and will be assigned to the intervention arm, Early Goal-Directed Sedation (EGDS) or the control arm, standard sedation practice (STDS). The intervention arm will consist of titrated light sedation with dexmedetomidine and minimisation of benzodiazepines. The standard care arm will consist of sedation at the clinician’s discretion with avoidance of dexmedetomidine except for agitation. Targeted light sedation will be recommended in the standard care group. Patient sedation levels will be assessed 4hrly and delirium daily. A telephone follow-up will be conducted at 90 days and 180 days.

Outcomes

Primary Endpoint

  • 90 day mortality

Secondary Endpoints include

  • Ventilation free days at 28 days following randomisation
  • Proportion of RASS measurements in target range
  • Incidence and duration of delirium
  • Mortality at ICU and hospital discharge
  • Length of ICU and hospital stay
  • Cognitive function and Health Related Quality of Life at 180 days
  • Cost effectiveness