An investigator-initiated, randomised, clinical, parallel-group, multinational, superiority trial

Financed by the Danish Strategic Research Council Identifier: NCT01967680

Protocol published at Trials


To assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients in ICU.


Randomised, clinical, parallel-group, multinational, superiority trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.

Inclusion criteria

  • Endotracheally intubated
  • Expected time on ventilator > 24 hours
  • Age ≥ 18 years
  • Informed consent

Exclusion criteria


  • Non-intubated patients
  • Patients with severe head trauma
  • Coma at admission or status epilepticus
  • Patients treated with therapeutic hypothermia
  • Patients with PaO2/FiO2<9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.


Randomization groups


  • Experimental intervention: Non-sedation supplemented with pain management during mechanical ventilation.
  • Control intervention: Sedation with a daily wake-up trial.


Primary Outcome

All-cause mortality at 90 days after randomization

Secondary outcomes

  • Days until death throughout the total observation period.
    • Proportion of patients with a major cardiovascular outcome (acute myocardial infarction, cerebral infarction, cerebral haemorrhage, pulmonary embolus, deep vein thrombosis, other thrombo-embolic event) at 90 days after randomisation.
  • Number of coma and delirium-free days
    • (defined as RASS ≥ -3 and no positive CAM-ICU scorings the particular day) within 28 days from randomisation
  • Highest Rifle-score within 28 days from randomization
  • Days until discharge from the intensive care unit
    • (within 28 days from randomisation).
  • Days until the participant is without mechanical ventilation
    • (within 28 days from randomisation).

Exploratory outcomes

  • All-cause mortality at 28 days after randomisation.
  • Days until discharge from the intensive care unit
    • (within 90 days from randomisation).
  • Days until the participant is without without mechanical ventilation
    • (within 90 days from randomisation).
  • Days until discharge from the hospital (within 90 days from randomisation).
  • Organ failure when the patient is discharged from the ICU.
  • Number of accidental extubations
    • (requiring re-intubation within 1 hour)
  • Number of accidental removals of central venous lines
    • (requiring re-insertion within 4 hours)


  • Three sub-studies will be carried out in 250 patients from the main trial examining:
  • Physical function
  • Cognitive function
  • Post-Traumatic Stress Disorder (PTSD)

Steering Committee

  • Palle Toft, Odense, Denmark.
  • Thomas Strøm, Odense, Denmark.
  • Hanne Tanghus Olsen, Svendborg, Denmark
  • Helene Korvenius Jørgensen, Kolding, Denmark