DeliriumPhase 2/3DahLIANCT01151865
Dexmedetomidine to Lessen Intensive Care Unit (ICU) Agitation
A Phase 2/3 study testing Dexmedetomidine in people with Delirium, run by Austin Health at 7 sites in Australia.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Delirium
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 96 participants
- Where
- 7 sitesAustralia
- Study dates
- Feb 2011to Dec 2013
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Australia7 sites
Northern Hospital
Epping, Victoria, 3076
The Western Hospital
Footscray, Victoria, 3011
Austin Hospital
Melbourne, Victoria, 3084
Royal Perth Hospital
Perth, Western Australia, 6001
The Alfred Hospital
Prahran, Victoria, 3181
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Toowoomba Hospital
Toowoomba, Queensland, 4350
About this study
Official title: A Randomised, Double-blind, Multi-centre Placebo Controlled Trial of Dexmedetomidine for Patients With Agitation and Delirium in the Intensive Care Unit
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
- Being tested
- Dexmedetomidine, Saline placebo
- Keywords
- Delirium, Intensive Care Unit, Dexmedetomidine
- Medical subject headings
- Delirium
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
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 placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Saline placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days following randomisation
Secondary outcomes (20)
Time to ICU discharge
Measured: On hospital discharge, or 6 months (whichever is sooner)
Overall ICU length of stay
Measured: On hospital discharge, or 6 months (whichever is sooner)
Time to first extubation
Measured: On hospital discharge, or 6 months (whichever is sooner)
Time taken to achieve a satisfactory sedation score
Time taken to achieve RASS score -2 to +1 and RIKER score 3 or 4
Measured: 7 days following randomisation
%ICU time spent with a satisfactory sedation score
%ICU time spent with RASS -2 to +1 and RIKER 3 or 4
Measured: 7 days following randomisation
%ICU time spent with a satisfactory delirium score
% time spent with a negative CAM-ICU assessment
Measured: 7 days following randomisation
Time taken to achieve a satisfactory agitation score
Time taken to achieve a MAAS score 2-4
Measured: 7 days following randomisation
%ICU time spent with a satisfactory agitation score
%ICU time spent with a MAAS score 2-4
Measured: 7 days following randomisation
Need for supplementary sedative medication
total infusion time, mean hourly dose and total dose of propofol, morphine and midazolam.
Measured: 7 days following randomisation
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
Measured: 7 days following randomisation
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
Measured: 7 days following randomisation
Need for tracheostomy
Tracheostomy deemed to be necessary by the treating physician, and actually performed.
Measured: On hospital discharge, or 6 months (whichever is sooner)
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.
Measured: On hospital discharge, or 6 months (whichever is sooner)
Discharge destination
Discharge to home, a skilled nursing facility, residential care, a physical rehabilitation facility, or death.
Measured: On hospital discharge, or 6 months (whichever is sooner)
Daily SOFA score
Daily SOFA score with recording of the component parts
Measured: 7 days following randomisation
ICU mortality
ICU mortality
Measured: On hospital discharge, or 6 months (whichever is sooner)
Hospital mortality
Death in the acute care hospital
Measured: On hospital discharge, or 6 months (whichever is sooner)
Duration and rate of vasopressor support
total infusion time, and mean hourly dose of noradrenaline and any other inotrope or vasopressor
Measured: 7 days following randomisation
Need for insertion of a new central venous catheter to facilitate vasopressor / inotropic support
Measured: 7 days following randomisation
Requirement for reintubation
Reintubation of the trachea to facilitate airway protection or mechanical ventilation, as indicated in the opinion of the treating physician
Measured: On hospital discharge, or 6 months (whichever is sooner)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2010 (estimated)
- Study startFeb 2011
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DeliriumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Austin Health
- Sponsor type
- Other government
- Collaborators
- Hospira, now a wholly owned subsidiary of Pfizer
- Responsible party
- Principal investigator, GLENN EASTWOOD, Austin Health
- Investigators
- Michael C Reade, MBBS DPhil, Study chair, Austin Hospital & University of MelbourneRinaldo Bellomo, MD, Principal investigator, Austin Hospital and University of MelbourneJohn Mulder, MBChB, Principal investigator, Western Hospital, MelbourneBen Cheung, MBBS, Principal investigator, Toowoomba HospitalAnthony Delaney, MBBS, Principal investigator, Royal North Shore HospitalAndrew Davis, MBBS, Principal investigator, The AlfredSteve Webb, MBBS, Principal investigator, Royal Perth HospitalMichael Bailey, MSc PhD, Principal investigator, Monash University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01151865
- Sponsor's protocol ID
- H2010/03891
- Acronym
- DahLIA
- Status last verified
- Jan 2015
- First submitted
- 18 Jun 2010
- Last updated
- 21 Jan 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 26975647
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Multi-centre Placebo Controlled Trial of Dexmedetomidine for Patients With Agitation and Delirium in the Intensive Care Unit
- ClinicalTrials.gov ID
- NCT01151865
- Acronym / sponsor ID
- DahLIA / H2010/03891
- Conditions
- Delirium
- Keywords
- Delirium, Intensive Care Unit, Dexmedetomidine
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Austin HealthOther government
- Collaborators
- Hospira, now a wholly owned subsidiary of Pfizer
- Study start
- Feb 2011
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 29 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dexmedetomidine | Active comparator | Drug: DexmedetomidineDexmedetomidine 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 | Placebo comparator | Drug: Saline placeboAn 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
- 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%.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineAlso: PrecedexDexmedetomidine 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 placeboAn 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. | Drug | Saline placebo |
Primary outcome
Ventilator-free hours
Time frame: 7 days following randomisation
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.
20 secondary outcomes
Time to ICU discharge
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Overall ICU length of stay
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Time to first extubation
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Time taken to achieve a satisfactory sedation score
Time frame: 7 days following randomisation
%ICU time spent with a satisfactory sedation score
Time frame: 7 days following randomisation
%ICU time spent with a satisfactory delirium score
Time frame: 7 days following randomisation
Time taken to achieve a satisfactory agitation score
Time frame: 7 days following randomisation
%ICU time spent with a satisfactory agitation score
Time frame: 7 days following randomisation
Need for supplementary sedative medication
Time frame: 7 days following randomisation
Need for mechanical restraint
Time frame: 7 days following randomisation
Need for supplementary antipsychotic medication
Time frame: 7 days following randomisation
Need for tracheostomy
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Acute hospital length of stay
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Discharge destination
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Daily SOFA score
Time frame: 7 days following randomisation
ICU mortality
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Hospital mortality
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Duration and rate of vasopressor support
Time frame: 7 days following randomisation
Need for insertion of a new central venous catheter to facilitate vasopressor / inotropic support
Time frame: 7 days following randomisation
Requirement for reintubation
Time frame: On hospital discharge, or 6 months (whichever is sooner)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jan 2015.
- Derived from this study: PubMed 26975647Reade 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.
Related trials for Delirium
RecruitingObservational study
The Impact of Fast-Track Anesthesia on Postoperative Neurocognitive Function in Patients Undergoing Cardiac Surgery
Delirium - Postoperative, Cardiac Surgery
Not yet recruiting
Prediction and Prevention of Postoperative Mortality and Morbidity
Dementia, Postoperative Delirium (POD)
Active, not recruitingPhase 3
The Danish Out-of-Hospital Cardiac Arrest Study
Out-Of-Hospital Cardiac Arrest, Post-Cardiac Arrest Syndrome
RecruitingPhase 3
Lactium Premedication to Prevent Emergence Agitation
Lactium, Premedication
Not yet recruiting
DEXmedetomidine for Postoperative Analgesia and Delirium Prevention After NEUROsurgery (DEX-NEURO Trial)
Neurosurgery, Brain Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael C Reade, MBBS DPhil study chair
Austin Hospital & University of Melbourne
Rinaldo Bellomo, MD principal investigator
Austin Hospital and University of Melbourne
John Mulder, MBChB principal investigator
Western Hospital, Melbourne
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dexmedetomidine in people with Delirium, run by Austin Health at 7 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventilator-free hours (time frame: 7 days following randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01151865, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2015.