Trial Review

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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 information initially 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] 251758 0
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 2518 0
Condition category
Condition code
Neurological 2613 2613 0 0
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] 2245 0
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] 3526 0
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] 3526 0
72 hours
Secondary outcome [1] 5880 0
Efficacy:
1.Time to discontinuation of therapy (hours)rescue usage
Timepoint [1] 5880 0
72 hours and various timepoints for follow-up data
Secondary outcome [2] 5881 0
Efficacy
Time to first rescue midazolam
Timepoint [2] 5881 0
Number of hours from administration of first study dose.
Secondary outcome [3] 5882 0
Efficacy
3.Number/total dosage of midazolam
Timepoint [3] 5882 0
Number of hours from administration of first study dose.
Secondary outcome [4] 5883 0
Serum apoptosis marker levels:
Timepoint [4] 5883 0
At the time of delirium resolution. Within the 3 days of intervention, or during the study follow-up period.
Secondary outcome [5] 5884 0
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] 5884 0
12 months
Secondary outcome [6] 5885 0
Toxicity:
1.Extrapyramidal toxicity:
Timepoint [6] 5885 0
72 hours
Secondary outcome [7] 5886 0
Toxicity
2.Sedation:
Timepoint [7] 5886 0
7 days
Secondary outcome [8] 5887 0
Toxicity
3.Adverse events
Timepoint [8] 5887 0
Twice daily for the 3 days of intervention.
Secondary outcome [9] 5888 0
Efficacy
4.Memorial Delirium Assessment Scale (MDAS) score < 7
Timepoint [9] 5888 0
72 hours
Secondary outcome [10] 5889 0
Efficacy
5.Patients who did not require rescue dosage
Timepoint [10] 5889 0
72 hours
Secondary outcome [11] 5890 0
6.Percentage of patients who have delirium recurrence after 48 hours of MDAS < 7.
Timepoint [11] 5890 0
48 hours of MDAS < 7
Secondary outcome [12] 5891 0
Efficacy
7.Time profile of Memorial Delirium Assessment Scale scores
Timepoint [12] 5891 0
Daily for 3 days
Secondary outcome [13] 5892 0
Efficacy
8.Patient reported recall after delirium resolution
Timepoint [13] 5892 0
48 hours after MDAS < 7
Secondary outcome [14] 5893 0
Efficacy
9.Patient rated distress after delirium resolution.
Timepoint [14] 5893 0
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] 5894 0
Efficacy
10.Caregiver rated distress.
Timepoint [15] 5894 0
Day 3
Secondary outcome [16] 5895 0
Efficacy
11.Nursing staff rated distress.
Timepoint [16] 5895 0
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?
No
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] 312 0
2050, 5041, 4101, 8006, 2164, 2310.

Funding & Sponsors
Funding source category [1] 2760 0
Government body
Name [1] 2760 0
Commonwealth Department of Health and Ageing
Country [1] 2760 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Flinders Drive
Bedford Park SA 5041
Country
Australia
Secondary sponsor category [1] 2493 0
Government body
Name [1] 2493 0
Commonwealth Department of Health and Ageing
Address [1] 2493 0
Canberra
Country [1] 2493 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4680 0
Repatriation General Hospital
Ethics committee address [1] 4680 0
Daws Road
Daw Park SA 5041
Ethics committee country [1] 4680 0
Australia
Date submitted for ethics approval [1] 4680 0
01/11/2007
Approval date [1] 4680 0
06/02/2008
Ethics approval number [1] 4680 0
EC00191
Ethics committee name [2] 5828 0
Peter MaCallum Cancer Centre Ethics Committee
Ethics committee address [2] 5828 0
St Andrews Place, East Melbourne, Vic, 8006
Ethics committee country [2] 5828 0
Australia
Date submitted for ethics approval [2] 5828 0
26/03/2008
Approval date [2] 5828 0
24/07/2008
Ethics approval number [2] 5828 0
EC00235
Ethics committee name [3] 5829 0
Flinders Cliical Research Ethics Committee
Ethics committee address [3] 5829 0
Flinders Medical Centre, Bedford Park, SA 5042
Ethics committee country [3] 5829 0
Australia
Date submitted for ethics approval [3] 5829 0
22/11/2007
Approval date [3] 5829 0
22/05/2008
Ethics approval number [3] 5829 0
EC00188
Ethics committee name [4] 5830 0
Mater Health Services Human Research Ethics Committee
Ethics committee address [4] 5830 0
Raymond Tce, South Brisbane, QLD, 4101
Ethics committee country [4] 5830 0
Australia
Date submitted for ethics approval [4] 5830 0
17/04/2008
Approval date [4] 5830 0
16/06/2008
Ethics approval number [4] 5830 0
EC00332
Ethics committee name [5] 5831 0
Cancer Institute NSW
Ethics committee address [5] 5831 0
PO Box 41, Alexandria, NSW, 1435
Ethics committee country [5] 5831 0
Australia
Date submitted for ethics approval [5] 5831 0
28/04/2008
Approval date [5] 5831 0
03/07/2008
Ethics approval number [5] 5831 0
EC00414
Ethics committee name [6] 258962 0
Ballarat Health Services & St John of God Health Care Ethics Committee
Ethics committee address [6] 258962 0
Medical Services
Ballarat Health Services
PO Box 577
BALLARAT VIC 3353
Ethics committee country [6] 258962 0
Australia
Date submitted for ethics approval [6] 258962 0
19/01/2009
Approval date [6] 258962 0
25/03/2009
Ethics approval number [6] 258962 0
EC00207
Ethics committee name [7] 258963 0
St John of God Health Care Ethics Committee
Ethics committee address [7] 258963 0
Level 3
St John of God House
177-179 Cambridge Street
WEMBLEY WA 6014
Ethics committee country [7] 258963 0
Date submitted for ethics approval [7] 258963 0
06/08/2009
Approval date [7] 258963 0
08/04/2010
Ethics approval number [7] 258963 0
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 28156 0
A/Prof Meera Agar
Address 28156 0
Braeside Hospital 340 Prairievale Rd Prairiewood NSW 2164 (Locked Bag 82 Wetherill Park 2164)
Country 28156 0
Australia
Phone 28156 0
+61 2 96168654
Fax 28156 0
+ 61-2-9616 8657
Email 28156 0
meera.agar@sswahs.nsw.gov.au
Contact person for public queries
Name 11313 0
A/Prof Meera Agar
Address 11313 0
Braeside Hospital 340 Prairievale Rd Prairiewood NSW 2164 (Locked Bag 82 Wetherill Park 2164)
Country 11313 0
Australia
Phone 11313 0
+61 2 96168654
Fax 11313 0
+ 61-2-9616 8657
Email 11313 0
meera.agar@sswahs.nsw.gov.au
Contact person for scientific queries
Name 2241 0
A/Prof Meera Agar
Address 2241 0
Braeside Hospital 340 Prairievale Rd Prairiewood NSW 2164 (Locked Bag 82 Wetherill Park 2164)
Country 2241 0
Australia
Phone 2241 0
+61 2 96168654
Fax 2241 0
+ 61-2-9616 8657
Email 2241 0
meera.agar@sswahs.nsw.gov.au

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 itcc@uts.edu.au. 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.TypeCitationLinkEmailOther DetailsAttachment
18862Informed consent form  itcc@uts.edu.au
18863Ethical approval  itcc@uts.edu.au
18864Study protocol  itcc@uts.edu.au
18865Clinical study report  itcc@uts.edu.au


Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes doi:10.1001/jamainternmed.2016.7491 Publication ... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseDrug therapy for delirium in terminally ill adults.2020https://dx.doi.org/10.1002/14651858.CD004770.pub3
EmbaseEfficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: A randomized clinical trial.2017https://dx.doi.org/10.1001/jamainternmed.2016.7491
EmbaseAntipsychotics for treatment of delirium in hospitalised non-ICU patients.2018https://dx.doi.org/10.1002/14651858.CD005594.pub3
EmbaseIn patients receiving palliative care, risperidone or haloperidol increased delirium symptoms vs placebo.2017https://dx.doi.org/10.7326/ACPJC-2017-166-6-032
N.B. These documents automatically identified may not have been verified by the study sponsor.