Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation

Delirium Clinical Trial

— DahLIA  

Official title:

A Randomised, Double-blind, Multi-centre Placebo Controlled Trial of Dexmedetomidine for Patients With Agitation and Delirium in the Intensive Care Unit

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01151865
• Other study ID #: H2010/03891
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: June 18, 2010
• Last updated: January 18, 2015
• Start date: February 2011
• Est. completion date: December 2013

Study information

• Verified date: January 2015
• Source: Austin Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Delirium

Intervention

Drug:
• Dexmedetomidine
Dexmedetomidine will be administered intravenously as a maintenance infusion of 0.2 to 1.5 mcg/kg/hour, commencing at 0.5 mcg/kg/hour and titrated according to effect, for as long as deemed necessary by the treating physician. Specifically, the study medication may be (as recommended by the manufacturer) continued after extubation, and if discontinued may be restarted at any time up until ICU discharge. The clinician will have the option of using a loading dose of 1.0 mcg/kg IV over 20 minutes, as recommended by the manufacturer. Bedside nursing staff will adjust drug infusion rates as necessary, in consultation with the treating physician, aiming to achieve a Riker Sedation-Agitation Scale 20 score of 4.
• Saline placebo
An identical syringe containing only saline with no dexmedetomidine added will be supplied. Initial rate of infusion and subsequent adjustments will be the same as in the active comparator group.

Locations

Country	Name	City	State
Australia	Northern Hospital	Epping	Victoria
Australia	The Western Hospital	Footscray	Victoria
Australia	Austin Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	The Alfred Hospital	Prahran	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland

Sponsors (2)

Lead Sponsor	Collaborator
Austin Health	Hospira, Inc.

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator-free hours	The primary outcome measure for the study will be 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 normal saline placebo while receiving all other aspects of standard care.	7 days following randomisation	Yes
Secondary	Time to ICU discharge		On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Overall ICU length of stay		On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Time to first extubation		On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Time taken to achieve a satisfactory sedation score	Time taken to achieve RASS score -2 to +1 and RIKER score 3 or 4	7 days following randomisation	Yes
Secondary	%ICU time spent with a satisfactory sedation score	%ICU time spent with RASS -2 to +1 and RIKER 3 or 4	7 days following randomisation	Yes
Secondary	%ICU time spent with a satisfactory delirium score	% time spent with a negative CAM-ICU assessment	7 days following randomisation	Yes
Secondary	Time taken to achieve a satisfactory agitation score	Time taken to achieve a MAAS score 2-4	7 days following randomisation	Yes
Secondary	%ICU time spent with a satisfactory agitation score	%ICU time spent with a MAAS score 2-4	7 days following randomisation	Yes
Secondary	Need for supplementary sedative medication	total infusion time, mean hourly dose and total dose of propofol, morphine and midazolam.	7 days following randomisation	Yes
Secondary	Need for mechanical restraint	Time to first not requiring restraint and % ICU time spent without mechanical restraint in the 7 days following commencement of trial medication	7 days following randomisation	Yes
Secondary	Need for supplementary antipsychotic medication	Number of doses and total mg delivered of haloperidol, olanzapine, quetiapine, or other anti-psychotic medication as prescribed by the treating physician	7 days following randomisation	Yes
Secondary	Need for tracheostomy	Tracheostomy deemed to be necessary by the treating physician, and actually performed.	On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Acute hospital length of stay	Total duration of admission to the acute hospital, prior to discharge to home or a skilled or unskilled nursing facility.	On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Discharge destination	Discharge to home, a skilled nursing facility, residential care, a physical rehabilitation facility, or death.	On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Daily SOFA score	Daily SOFA score with recording of the component parts	7 days following randomisation	Yes
Secondary	ICU mortality	ICU mortality	On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Hospital mortality	Death in the acute care hospital	On hospital discharge, or 6 months (whichever is sooner)	Yes
Secondary	Duration and rate of vasopressor support	total infusion time, and mean hourly dose of noradrenaline and any other inotrope or vasopressor	7 days following randomisation	Yes
Secondary	Need for insertion of a new central venous catheter to facilitate vasopressor / inotropic support		7 days following randomisation	Yes
Secondary	Requirement for reintubation	Reintubation of the trachea to facilitate airway protection or mechanical ventilation, as indicated in the opinion of the treating physician	On hospital discharge, or 6 months (whichever is sooner)	Yes