Clinical trial NCT01151865: Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation
Official title: A Randomised, Double-blind, Multi-centre Placebo Controlled Trial of Dexmedetomidine for Patients With Agitation and Delirium in the Intensive Care Unit
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Delirium
Keywords: Delirium
Intensive Care Unit
Dexmedetomidine
Lead sponsor: Austin Health
Sponsor class: OTHER_GOV
Collaborators: name: Hospira, now a wholly owned subsidiary of Pfizer
First posted: 2010-06-29
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary aim of the DahLIA trial is to determine, in patients with ICU-associated delirium and agitation who are otherwise pathophysiologically stable (as defined), the number of ventilator-free hours in the incident ICU admission in the 7 days following commencement of trial medication, in patients randomised to receive dexmedetomidine or placebo while receiving all other aspects of standard care.

The null hypothesis assumes no difference in the median number of ventilator-free hours in this ICU admission in the following 7 days, between patients receiving dexmedetomidine and placebo for ICU-associated agitation and delirium.


Eligibility criteria: Inclusion Criteria:

Patients will be eligible for the study if, in the opinion of the treating clinician, they continue to require mechanical ventilation only because their degree of agitation requires such a high dose of sedative medication (midazolam or propofol, the only commonly used specific sedatives in our unit) that extubation is not possible, AND in the opinion of their treating intensivist their agitation is so severe as to make lessening their sedation unsafe.

These criteria will be objectively quantified as follows:

* they have required either mechanical restraint and/or anti-delirium or sedative medication in the 4 hours prior to seeking consent AND
* their Confusion Assessment Method for the ICU (CAM-ICU) test is positive for delirium in the 4 hours prior to seeking consent AND
* their Motor Activity Assessment Scale (MAAS) score is 5 or more in the 4 hours prior to seeking consent, confirming psychomotor agitation AND
* their SOFA score is less than or equal to 5 in the 4 hours prior to seeking consent, predicting a mortality or around 5%.

Exclusion Criteria:

* Age less than 18 years old
* Pregnancy or breastfeeding
* Advanced dementia (in the premorbid state requiring professional nursing care)
* Open or closed head injury
* Death is deemed imminent and inevitable
* The patient has previously been enrolled in the DahLIA study
* Patients who could not be extubated, or who would be intubated within the following 48 hours, even if delirium or agitation were corrected. This will include:

  * Patients receiving high dose opioid for analgesia (not sedation) ( \> 40 mg/morphine/day)
  * Patients shortly to return to the operating theatre
  * Patients undergoing repeated invasive procedures, in whom it is desirable to maintain deep sedation
  * Patients likely to require ongoing airway protection or control, or ventilatory support (for example, spinal patients with an inadequate vital capacity)
* Known allergy to haloperidol or alpha 2 agonists

Primary outcomes:
measure: Ventilator-free hours
timeFrame: 7 days following randomisation
Secondary outcomes:
measure: Time to ICU discharge
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Overall ICU length of stay
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Time to first extubation
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Time taken to achieve a satisfactory sedation score
timeFrame: 7 days following randomisation
measure: %ICU time spent with a satisfactory sedation score
timeFrame: 7 days following randomisation
measure: %ICU time spent with a satisfactory delirium score
timeFrame: 7 days following randomisation
measure: Time taken to achieve a satisfactory agitation score
timeFrame: 7 days following randomisation
measure: %ICU time spent with a satisfactory agitation score
timeFrame: 7 days following randomisation
measure: Need for supplementary sedative medication
timeFrame: 7 days following randomisation
measure: Need for mechanical restraint
timeFrame: 7 days following randomisation
measure: Need for supplementary antipsychotic medication
timeFrame: 7 days following randomisation
measure: Need for tracheostomy
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Acute hospital length of stay
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Discharge destination
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Daily SOFA score
timeFrame: 7 days following randomisation
measure: ICU mortality
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Hospital mortality
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
measure: Duration and rate of vasopressor support
timeFrame: 7 days following randomisation
measure: Need for insertion of a new central venous catheter to facilitate vasopressor / inotropic support
timeFrame: 7 days following randomisation
measure: Requirement for reintubation
timeFrame: On hospital discharge, or 6 months (whichever is sooner)
Other outcomes:
Locations:
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Epping
country: Australia
facility: Northern Hospital
state: Victoria
city: Footscray
country: Australia
facility: The Western Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Austin Hospital
state: Victoria
city: Prahran
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
Study officials:
affiliation: Austin Hospital & University of Melbourne
name: Michael C Reade, MBBS DPhil
role: STUDY_CHAIR
affiliation: Austin Hospital and University of Melbourne
name: Rinaldo Bellomo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Western Hospital, Melbourne
name: John Mulder, MBChB
role: PRINCIPAL_INVESTIGATOR
affiliation: Toowoomba Hospital
name: Ben Cheung, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal North Shore Hospital
name: Anthony Delaney, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: The Alfred
name: Andrew Davis, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Perth Hospital
name: Steve Webb, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Monash University
name: Michael Bailey, MSc PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Austin Hospital, Melbourne Australia
name: Glenn Eastwood, BNurs RN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Effect of Dexmedetomidine Added to Standard Care on Ventilator-Free Time in Patients With Agitated Delirium: A Randomized Clinical Trial. JAMA. 2016 Apr 12;315(14):1460-8. doi: 10.1001/jama.2016.2707.