ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12607000562471

Ethics application status

Approved

Date submitted

30/10/2007

Date registered

1/11/2007

Date last updated

13/04/2023

Date data sharing statement initially provided

13/04/2023

Date results provided

13/04/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Oral risperidone, oral haloperidol, and oral placebo in the management of delirium in palliative care.

Scientific title

Oral risperidone, oral haloperidol, and oral placebo in the management of delirium in palliative care.

Secondary ID [1]

002/07

Universal Trial Number (UTN)

Trial acronym

Risperidone and haloperidol in delirium

Linked study record

Health condition

Health condition(s) or problem(s) studied:

delirium

Condition category

Condition code

Neurological

Dementias

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Oral risperidone (0.5 to 2mg according to response) twice daily for 3 days, vs oral haloperidol twice daily (0.5 to 2mg according to response) for 3 days.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Oral placebo syrup (water and preservative, standared base for the study drugs) twice daily for 3 days.

Control group

Placebo

Outcomes

Primary outcome [1]

Sum of scores on Nursing Delirium screening scale - items 2 (inappropriate behaviour), 3 (inappropriate communication), and 4 (illusions/hallucinations). The primary null hypothesis is no difference between oral risperidone and ora placebo at 72 hours from treatment commencement.

Timepoint [1]

72 hours

Secondary outcome [1]

Efficacy:
1.Time to discontinuation of therapy (hours)rescue usage

Timepoint [1]

72 hours and various timepoints for follow-up data

Secondary outcome [2]

Efficacy
Time to first rescue midazolam

Timepoint [2]

Number of hours from administration of first study dose.

Secondary outcome [3]

Efficacy
3.Number/total dosage of midazolam

Timepoint [3]

Number of hours from administration of first study dose.

Secondary outcome [4]

Serum apoptosis marker levels:

Timepoint [4]

At the time of delirium resolution. Within the 3 days of intervention, or during the study follow-up period.

Secondary outcome [5]

Health service utilisation and long term outcomes:
1.Medical complications during admission
2.Death.
3.Cognitive impairment
4.Functional decline.
5.Usage of Assistants in Nursing (hours) during delirium episode.
6.Nursing home placement.
7.Length of admission in palliative care unit (days).
8.Survival outside of institutional care (days).

Timepoint [5]

12 months

Secondary outcome [6]

Toxicity:
1.Extrapyramidal toxicity:

Timepoint [6]

72 hours

Secondary outcome [7]

Toxicity
2.Sedation:

Timepoint [7]

7 days

Secondary outcome [8]

Toxicity
3.Adverse events

Timepoint [8]

Twice daily for the 3 days of intervention.

Secondary outcome [9]

Efficacy
4.Memorial Delirium Assessment Scale (MDAS) score < 7

Timepoint [9]

72 hours

Secondary outcome [10]

Efficacy
5.Patients who did not require rescue dosage

Timepoint [10]

72 hours

Secondary outcome [11]

6.Percentage of patients who have delirium recurrence after 48 hours of MDAS < 7.

Timepoint [11]

48 hours of MDAS < 7

Secondary outcome [12]

Efficacy
7.Time profile of Memorial Delirium Assessment Scale scores

Timepoint [12]

Daily for 3 days

Secondary outcome [13]

Efficacy
8.Patient reported recall after delirium resolution

Timepoint [13]

48 hours after MDAS < 7

Secondary outcome [14]

Efficacy
9.Patient rated distress after delirium resolution.

Timepoint [14]

At time of delirium resolution, this may be within the 3 days of the study intervention, or during the follow-up period.

Secondary outcome [15]

Efficacy
10.Caregiver rated distress.

Timepoint [15]

Day 3

Secondary outcome [16]

Efficacy
11.Nursing staff rated distress.

Timepoint [16]

Day 3

Eligibility

Key inclusion criteria

• Diagnosis of Delirium as defined by Diagnostic and Statistical Manual of Mental Disorders (DSM IVR) criteria for delirium ( a standard diagnotic manual for defining mental disorders) and MDAS score
• Score on Nursing Delirium screening scale
• English speaking.
• Proxy written informed consent.
• Cancer or non-cancer life limiting illness.

Minimum age

18 Years

Maximum age

Not stated

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

• Delirium due to alcohol or other withdrawal syndrome where more specific treatment is indicated.
• Current or past history of neuroleptic malignant syndrome.
• Antipsychotic use within past 7 days.
• Maintenance on antipsychotic required for other diagnosis.
• Previous adverse reaction to any of the study medications.
• Established Parkinson’s disease or other extrapyramidal disorder.
• Documented prolonged QT (QT is the relationship between two conduction points on an electrocardiograph (ECG) syndrome
• Clinician predicted survival less than seven days.
• Cerebrovascular accident with in the last month.
• Seizure within the last month.
• Pregnant or breastfeeding.

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

At each centre, patients will be sequentially allocated a patient number on referral to the study. This ID number will be used for all subsequent study documentation for that participant.

On notification of a participant, the pharmacist at each site will allocate the next code available according to the supplied schedule and prepare the active or inactive drug delivered in a labeled opaque screw top bottle. The participant ID, allocation code, dates of request, preparation, and dispensing will be recorded in a log maintained by the pharmacist and supplied to the central registry on each randomisation.
At all times, from eligibility screening to completion of the study, all study staff are unaware of the treatment allocation. Allocation is concealed from the investigator at the time of the participant inclusion in the trial, the allocation is determined by contacting the site pharmacy.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomisation schedules will be developed for each site using random number tables, generated at an independent centre (central registry). Treatment for each patient will be allocated according to a block randomisation schedule held by the central registry in a 1:1:1 ratio. Block randomisation will ensure even allocation to each code in each site. The central registry will supply the schedule tables to each site pharmacy.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/05/2008

Actual

13/08/2008

Date of last participant enrolment

Anticipated

Actual

2/04/2014

Date of last data collection

Anticipated

Actual

24/04/2014

Sample size

Target

165

Accrual to date

Final

171

Recruitment in Australia

Recruitment state(s)

NSW,QLD,SA,VIC

Recruitment postcode(s) [1]

2050, 5041, 4101, 8006, 2164, 2310.

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Commonwealth Department of Health and Ageing

Address [1]

Canberra

Country [1]

Australia

Primary sponsor type

University

Name

Flinders University

Address

Flinders Drive
Bedford Park SA 5041

Country

Australia

Secondary sponsor category [1]

Government body

Name [1]

Commonwealth Department of Health and Ageing

Address [1]

Canberra

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Repatriation General Hospital

Ethics committee address [1]

Daws Road
Daw Park SA 5041

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

01/11/2007

Approval date [1]

06/02/2008

Ethics approval number [1]

EC00191

Ethics committee name [2]

Peter MaCallum Cancer Centre Ethics Committee

Ethics committee address [2]

St Andrews Place, East Melbourne, Vic, 8006

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

26/03/2008

Approval date [2]

24/07/2008

Ethics approval number [2]

EC00235

Ethics committee name [3]

Flinders Cliical Research Ethics Committee

Ethics committee address [3]

Flinders Medical Centre, Bedford Park, SA 5042

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

22/11/2007

Approval date [3]

22/05/2008

Ethics approval number [3]

EC00188

Ethics committee name [4]

Mater Health Services Human Research Ethics Committee

Ethics committee address [4]

Raymond Tce, South Brisbane, QLD, 4101

Ethics committee country [4]

Australia

Date submitted for ethics approval [4]

17/04/2008

Approval date [4]

16/06/2008

Ethics approval number [4]

EC00332

Ethics committee name [5]

Cancer Institute NSW

Ethics committee address [5]

PO Box 41, Alexandria, NSW, 1435

Ethics committee country [5]

Australia

Date submitted for ethics approval [5]

28/04/2008

Approval date [5]

03/07/2008

Ethics approval number [5]

EC00414

Ethics committee name [6]

Ballarat Health Services & St John of God Health Care Ethics Committee

Ethics committee address [6]

Medical Services
Ballarat Health Services
PO Box 577
BALLARAT VIC 3353

Ethics committee country [6]

Australia

Date submitted for ethics approval [6]

19/01/2009

Approval date [6]

25/03/2009

Ethics approval number [6]

EC00207

Ethics committee name [7]

St John of God Health Care Ethics Committee

Ethics committee address [7]

Level 3
St John of God House
177-179 Cambridge Street
WEMBLEY WA 6014

Ethics committee country [7]

Date submitted for ethics approval [7]

06/08/2009

Approval date [7]

08/04/2010

Ethics approval number [7]

EC00286

Summary

Brief summary

Delirium is prevalent in patients with advanced cancer and in the palliative care setting, and is associated with significant and distressing symptomatology and poor prognosis. Antipsychotics are considered by most clinicians as first line pharmacotherapeutic agents for delirium despite limited randomized double blind controlled evidence for management of delirium in any health care setting, including palliative care. The few studies that exist explore post treatment efficacy in relation to total delirium score reduction, and do not guide management of target symptomatology. There as been no systematic evaluation of toxicity profile in relation to delirium management with typical or atypical antipsychotics, in particular extrapyramidal toxicity and degree of sedation. There is need for randomized control trial evidence of the efficacy of antipsychotics to control targeted delirium symptoms, and also to consider broader implications on caregiver and patient distress.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

A/Prof Meera Agar

Address

Braeside Hospital 340 Prairievale Rd Prairiewood NSW 2164 (Locked Bag 82 Wetherill Park 2164)

Country

Australia

Phone

+61 2 96168654

Fax

+ 61-2-9616 8657

[email protected]

Contact person for public queries

Name

Meera Agar

Address

Braeside Hospital 340 Prairievale Rd Prairiewood NSW 2164 (Locked Bag 82 Wetherill Park 2164)

Country

Australia

Phone

+61 2 96168654

Fax

+ 61-2-9616 8657

[email protected]

Contact person for scientific queries

Name

Meera Agar

Address

Braeside Hospital 340 Prairievale Rd Prairiewood NSW 2164 (Locked Bag 82 Wetherill Park 2164)

Country

Australia

Phone

+61 2 96168654

Fax

+ 61-2-9616 8657

[email protected]

Data sharing statement

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

Yes

What data in particular will be shared?

Individual Participant Data

When will data be available (start and end dates)?

01/06/2023 to 01/06/2031

Available to whom?

Researchers undertaking secondary research

Available for what types of analyses?

Those analyses described in approved proposals only

How or where can data be obtained?

Anyone who wishes to access the data should submit a proposal to [email protected]. If approved, data requestors will need to sign a data access agreement. After that, the ITCC Data Center will transfer the requested data and other documents to data requestors.

What supporting documents are/will be available?

Doc. No.	Type	Email
18862	Informed consent form	[email protected]
18863	Ethical approval	[email protected]
18864	Study protocol	[email protected]
18865	Clinical study report	[email protected]

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	Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: A randomized clinical trial.	2017	https://dx.doi.org/10.1001/jamainternmed.2016.7491
Embase	In patients receiving palliative care, risperidone or haloperidol increased delirium symptoms vs placebo.	2017	https://dx.doi.org/10.7326/ACPJC-2017-166-6-032
Embase	Antipsychotics for treatment of delirium in hospitalised non-ICU patients.	2018	https://dx.doi.org/10.1002/14651858.CD005594.pub3
Embase	Drug therapy for delirium in terminally ill adults.	2020	https://dx.doi.org/10.1002/14651858.CD004770.pub3

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

Trial Review

Documents added manually

Documents added automatically