Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation

NCT ID: NCT01151865

Last Updated: 2015-01-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2013-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine

Intervention Type: 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.

Saline placebo

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.

Group Type: PLACEBO_COMPARATOR

Saline placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Precedex

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospira, now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Austin Health

OTHER_GOV

Sponsor Role: lead

Responsible Party

GLENN EASTWOOD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael C Reade, MBBS DPhil

Role: STUDY_CHAIR

Austin Hospital & University of Melbourne

Rinaldo Bellomo, MD

Role: PRINCIPAL_INVESTIGATOR

Austin Hospital and University of Melbourne

John Mulder, MBChB

Role: PRINCIPAL_INVESTIGATOR

Western Hospital, Melbourne

Ben Cheung, MBBS

Role: PRINCIPAL_INVESTIGATOR

Toowoomba Hospital

Anthony Delaney, MBBS

Role: PRINCIPAL_INVESTIGATOR

Royal North Shore Hospital

Andrew Davis, MBBS

Role: PRINCIPAL_INVESTIGATOR

The Alfred

Steve Webb, MBBS

Role: PRINCIPAL_INVESTIGATOR

Royal Perth Hospital

Michael Bailey, MSc PhD

Role: PRINCIPAL_INVESTIGATOR

Monash University

Glenn Eastwood, BNurs RN

Role: PRINCIPAL_INVESTIGATOR

Austin Hospital, Melbourne Australia

Locations

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Toowoomba Hospital

Toowoomba, Queensland, Australia

Northern Hospital

Epping, Victoria, Australia

The Western Hospital

Footscray, Victoria, Australia

Austin Hospital

Melbourne, Victoria, Australia

The Alfred Hospital

Prahran, Victoria, Australia

Royal Perth Hospital

Perth, Western Australia, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 26975647 (View on PubMed)

Other Identifiers

H2010/03891

Identifier Type: -

Identifier Source: org_study_id