ANZCTR - Registration

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers

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

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]

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

Condition category

Condition code

Neurological

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]

Treatment: Drugs

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Change in delirium measured on Memorial Delirium Assessment Scale (MDAS), with NuDESC informing metric

Timepoint [1]

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]

Change in sedation measured on RASS score

Timepoint [1]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW

Recruitment hospital [1]

Port Kembla Hospital - Warrawong

Recruitment postcode(s) [1]

2502 - Warrawong

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Palliative Care Department, Port Kembla Hospital

Address [1]

Port Kembla Hospital, 89-91 Cowper Street Warrawong, New South Wales 2502

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Joint University of Wollongong and Illawarra Shoalhaven Local Health District Health and Medical Human Research Ethics Committee

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

18/05/2018

Approval date [1]

20/07/2018

Ethics approval number [1]

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

Dr Benjamin Thomas

Address

Palliative Care Department, The Wollongong Hospital, Crown Street, Wollongong, NSW 2500

Country

Australia

Phone

+61 2 4222 5000

Fax

+61 2 4222 5702

benjamin.thomas@health.nsw.gov.au

Contact person for public queries

Name

Benjamin Thomas

Address

Palliative Care Department, The Wollongong Hospital, Crown Street, Wollongong, NSW 2500

Country

Australia

Phone

+61 2 4222 5000

Fax

+61 2 4222 5702

benjamin.thomas@health.nsw.gov.au

Contact person for scientific queries

Name

Benjamin Thomas

Address

Palliative Care Department, The Wollongong Hospital, Crown Street, Wollongong, NSW 2500

Country

Australia

Phone

+61 2 4222 5000

Fax

+61 2 4222 5702

benjamin.thomas@health.nsw.gov.au

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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 Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Dexmedetomidine for hyperactive delirium at the end of life: An open-label single arm pilot study with dose escalation in adult patients admitted to an inpatient palliative care unit.	2021	https://dx.doi.org/10.1177/0269216321994440

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Registering a new trial?

Documents added manually

Documents added automatically