Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation

NCT01151865 | Completed Phase 2 DMC

• 1 other identifier: H2010/03891
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 7

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.

Conditions

Delirium

Keywords

Delirium; Intensive Care Unit; Dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (20)

• Time to ICU discharge

  On hospital discharge, or 6 months (whichever is sooner)

• Overall ICU length of stay

  On hospital discharge, or 6 months (whichever is sooner)

• Time to first extubation

  On hospital discharge, or 6 months (whichever is sooner)

• Time taken to achieve a satisfactory sedation score

  7 days following randomisation

• %ICU time spent with a satisfactory sedation score

  7 days following randomisation

Study Arms (2)

Dexmedetomidine

ACTIVE COMPARATOR

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.

Drug: Dexmedetomidine

Saline placebo

PLACEBO COMPARATOR

An identical syringe to that in the intervention arm, but which does not contain dexmedetomidine, will be provided. The initial rate of infusion and subsequent adjustments will be the same as in the dexmedetomidine group.

Drug: Saline placebo

Interventions

Dexmedetomidine DRUG

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.

Also known as: Precedex

Dexmedetomidine

Saline placebo DRUG

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.

Saline placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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

Sponsors & Collaborators

• Austin Health: lead
• Hospira, now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (7)

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

Location

Northern Hospital

Epping, Victoria, 3076, Australia

Location

The Western Hospital

Footscray, Victoria, 3011, Australia

Location

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

The Alfred Hospital

Prahran, Victoria, 3181, Australia

Location

Royal Perth Hospital

Perth, Western Australia, 6001, Australia

Location

Related Publications (1)

• 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.

  PMID: 26975647 DERIVED

MeSH Terms

Conditions

Delirium

Interventions

Dexmedetomidine

Condition Hierarchy (Ancestors)

Confusion; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Michael C Reade, MBBS DPhil

  Austin Hospital & University of Melbourne

  STUDY CHAIR

• Rinaldo Bellomo, MD

  Austin Hospital and University of Melbourne

  PRINCIPAL INVESTIGATOR

• John Mulder, MBChB

  Western Hospital, Melbourne

  PRINCIPAL INVESTIGATOR

• Ben Cheung, MBBS

  Toowoomba Hospital

  PRINCIPAL INVESTIGATOR

• Anthony Delaney, MBBS

  Royal North Shore Hospital

  PRINCIPAL INVESTIGATOR

• Andrew Davis, MBBS

  The Alfred

  PRINCIPAL INVESTIGATOR

• Steve Webb, MBBS

  Royal Perth Hospital

  PRINCIPAL INVESTIGATOR

• Michael Bailey, MSc PhD

  Monash University

  PRINCIPAL INVESTIGATOR

• Glenn Eastwood, BNurs RN

  Austin Hospital, Melbourne Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 18, 2010
• First Posted: June 29, 2010
• Study Start: February 1, 2011
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: January 21, 2015

Record last verified: 2015-01

Locations

AU (7)