Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000658213
Ethics application status
Approved
Date submitted
22/04/2018
Date registered
24/04/2018
Date last updated
9/06/2020
Date data sharing statement initially provided
27/03/2019
Date results information initially provided
9/06/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Dexmedetomidine in delirium at the end of life
Scientific title
Dexmedetomidine for delirium at the end of life: an open-label single arm study with dose escalation for terminal delirium in patients admitted to an inpatient palliative care unit
Secondary ID [1] 294511 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Delirium at the end of life 307281 0
Condition category
Condition code
Neurological 306401 306401 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Subcutaneous Dexmedetomidine infusion at End of Life

For patients approaching the end of life with delirium, dexmedetomidine will be administered by a continuous subcutaneous infusion (CSCI). Infusion will be given as a 2-tier protocol. Effect of dexmedetomidine will be assessed by delirium scoring (diagnosed with MDAS tool by treating clinician and assessed be MDAS daily, in addition to NuDESC ongoing in domains of inappropriate communication, illusions and hallucination, inappropriate behaviours). Rousability will be assessed by RASS scoring.

Tier 1 
0.3microg/kg (to nearest 10kg bodyweight, rounded down) for 24 hours via CSCI. If effective at controlling delirium (MDAS <13, NuDESC 2 or less in above domains, minimum rescue medication) with reasonable sedative scores (RASS score between -1 and -3), will maintain. If not, escalate to Tier 2.

Tier 2
0.6microg/kg (to nearest 10kg bodyweight, rounded down) for 24 hours via CSCI. If effective at controlling delirium (MDAS <13, NuDESC 2 or less in above domains, minimum rescue medication) with reasonable sedative scores (RASS score between -1 and -3), maintain dosing. If ineffective. withdraw dexmedetomidine and institute prior standard care for terminal delirium.

Doses will be calibrated to nearest 10microg/24 hours.

For both tiers:
1. Access to rescue medication (as required midazolam subcutaneous injection and haloperidol subcutaneous injection) will be ensured
2. Reversible causes of delirium will be assessed and treated in line with goals of care
3. Bowel and bladder function will be assessed and normalised as possible
4. Dexamedetomidine will be administered via continuous subcutaneous infusion pump (syringe driver), prescribed by the treating physician and administered by the ward nurses.
5. Maximum duration of infusion will be until death (expected maximum 10 days)
6. Crossover to standard care if consent withdrawn or at clinical concerns, side effects mandate, ineffective treatment.
Intervention code [1] 300814 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305620 0
Change in delirium measured on Memorial Delirium Assessment Scale (MDAS), with NuDESC informing metric
Timepoint [1] 305620 0
Up to 10 days post initiation of dexmedetomidine infusion Assessments will be performed every 8 hours (once per nursing shift for NuDESC and daily for MDAS)
Secondary outcome [1] 345931 0
Change in sedation measured on RASS score
Timepoint [1] 345931 0
Up to 10 days post initiation of dexmedetomidine infusion
Assessments will be performed every 8 hours (once per nursing shift).

Eligibility
Key inclusion criteria
Admitted to the Port Kembla Palliative Care Unit at Illawarra Shoalhaven Local Health District
English Speaking
Develop a terminal delirium during admission
End of life
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Non English speaking
Severe left ventricular dysfunction of <20% EF
Severe renal failure of eGFR of 30 or less
Severe hepatic failure with MELD score of 30 or greater
Bradycardia with restring heart rate of <65 BPM on screening

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
15/10/2018
Actual
7/11/2018
Date of last participant enrolment
Anticipated
Actual
20/05/2020
Date of last data collection
Anticipated
Actual
27/05/2020
Sample size
Target
22
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 10776 0
Port Kembla Hospital - Warrawong
Recruitment postcode(s) [1] 22514 0
2502 - Warrawong

Funding & Sponsors
Funding source category [1] 299137 0
Hospital
Name [1] 299137 0
Palliative Care Department, Port Kembla Hospital
Country [1] 299137 0
Australia
Primary sponsor type
Government body
Name
Illawarra Shoalhaven Local Health District
Address
PO Box 239
PORT KEMBLA NSW 2505
Country
Australia
Secondary sponsor category [1] 298396 0
None
Name [1] 298396 0
Address [1] 298396 0
Country [1] 298396 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300203 0
Joint University of Wollongong and Illawarra Shoalhaven Local Health District Health and Medical Human Research Ethics Committee
Ethics committee address [1] 300203 0
Ethics committee country [1] 300203 0
Australia
Date submitted for ethics approval [1] 300203 0
18/05/2018
Approval date [1] 300203 0
20/07/2018
Ethics approval number [1] 300203 0
2018/247

Summary
Brief summary
Patients near the end of life may suffer from delirium that can be difficult to control; with up to 88% of inpatients in palliative care units suffering from a terminal delirium. The current practice within the Illawarra Shoalhaven Local Health District (ISLHD) for patients suffering from a terminal delirium is to first attempt to reverse or treat any causes found, such as urinary retention and pain. If delirium proves to be irreversible, patients are typically given a continuous subcutaneous infusion (CSCI) of a benzodiazepine (midazolam), often in combination with an antipsychotic medication (haloperidol), with the aim of providing sedation to alleviate distress. If these medications are unable to alleviate a terminal delirium, the medication can be altered to include an infusion of levomepromazine, an antipsychotic, or phenobarbital, a barbiturate. With the above regimen, the majority of patients with terminal agitation will find symptom relief but will often become unable to eat, drink or interact with their loved ones.

Patients who currently suffer with terminal delirium admitted to the Port Kembla palliative care unit are provided with symptom relief via CSCI of midazolam infusion, with escalation to other agents per the European Association of Palliative Care (EAPC) framework for sedation in palliative medicine. Prognosis for patients with a terminal delirium is measured in a number of days to a week, and rarely extends beyond that timeframe. Patients suffering from worsening delirium and agitation, however, are often still verbal but the intractable nature of their suffering means that deeper sedation is the only current way available to provide them peace and dignity. Access to an option that may provide some resolution of the delirium without as deep a sedation so that the patient could interact with family and friends would be of benefit in these circumstances.

Dexmedetomidine is a novel agent for managing intractable symptoms in palliative medicine towards the end of life. It has the attribute of decreasing the frequency and severity of delirium, as well as analgesic benefits to assist in the management of pain and delirium. Of particular interest to patients towards the end of life who would like to continue to communicate with loved ones and be involved in decision-making is the potential ability to be woken when dexmedetomidine is utilised for sedation instead of midazolam, levomepromazine or phenobarbital. These features have been well studied in anaesthesia and in the ICU, with only case reports in palliative medicine.

Given the gap in knowledge we propose a Phase 2 trial for the utilisation of dexmedetomidine via CSCI in patients with a terminal delirium in an inpatient palliative care unit.

The goal of this study is to answer the following question: does dexmedetomidine provide effective relief from confusion and delirium at the end of life, with rousability, as assessed on standardised delirium and rousability scores
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82458 0
Dr Benjamin Thomas
Address 82458 0
Palliative Care Department, The Wollongong Hospital, Crown Street, Wollongong, NSW 2500
Country 82458 0
Australia
Phone 82458 0
+61 2 4222 5000
Fax 82458 0
+61 2 4222 5702
Email 82458 0
benjamin.thomas@health.nsw.gov.au
Contact person for public queries
Name 82459 0
Dr Benjamin Thomas
Address 82459 0
Palliative Care Department, The Wollongong Hospital, Crown Street, Wollongong, NSW 2500
Country 82459 0
Australia
Phone 82459 0
+61 2 4222 5000
Fax 82459 0
+61 2 4222 5702
Email 82459 0
benjamin.thomas@health.nsw.gov.au
Contact person for scientific queries
Name 82460 0
Dr Benjamin Thomas
Address 82460 0
Palliative Care Department, The Wollongong Hospital, Crown Street, Wollongong, NSW 2500
Country 82460 0
Australia
Phone 82460 0
+61 2 4222 5000
Fax 82460 0
+61 2 4222 5702
Email 82460 0
benjamin.thomas@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Ethics approval only covers use of the data by the research team
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary