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Trial registered on ANZCTR


Registration number
ACTRN12624001075572
Ethics application status
Approved
Date submitted
16/08/2024
Date registered
5/09/2024
Date last updated
5/09/2024
Date data sharing statement initially provided
5/09/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A single centre pilot randomised controlled trial of enteral Guanfacine vs Quetiapine for agitated delirium in patients in the intensive care unit
Scientific title
A single centre pilot randomised controlled trial of enteral Guanfacine vs Quetiapine for agitated delirium in patients in the intensive care unit
Secondary ID [1] 312054 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Agitated delirium 333663 0
Condition category
Condition code
Neurological 330352 330352 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients allocated to the intervention group will receive guanfacine for the treatment of agitated delirium. Guanfacine hydrochloride will be a single 2 mg dose given once a day via the oral route at the discretion of the treating ICU doctor for a maximum of 7 days while the patient is in ICU. From enrolment until day 8, treating ICU doctors will be permitted to use medication other than quetiapine for the treatment of delirium/agitation should it become necessary. On day 8 and onwards, the choice of anti-psychotic drug/agent will be at the discretion of the treating ICU doctors. Adherence will be monitored by review of medical records. All other aspects of care will conform to usual ICU practice. Blood pressure, heart rate will be monitored continuously and heart-rate corrected QT interval will be monitored as per usual routine care in intensive care unit. Usual practice in the intensive care unit of this study is for the treating medical team to prescribe medicines for the management of agitated delirium at their discretion and with the choice, dose and frequency also at their discretion.
Intervention code [1] 328499 0
Treatment: Drugs
Comparator / control treatment
Patients in the control group will receive quetiapine as the primary care for treatment of agitation. Quetiapine will be started at a dose of 25 - 50 mg given once daily via enteral route. The dose will be titrated to efficacy and safety which is a maximum dose of 100 mg/day. There will otherwise be no deviation from routine ICU management.
Control group
Active

Outcomes
Primary outcome [1] 338116 0
For the composite outcome, our definition of hours of alive and agitation/coma-free is the number of hours in the first 7 days after the patient was randomly assigned to receive the guanfacine or quetiapine during which the patient is alive without agitation and not in drug induced coma (i.e. with a Richmond Agitation and Sedation scale (RASS) score of -2 to zero).
Timepoint [1] 338116 0
RASS score is recorded six hourly and reported in the electronic medical record.
Secondary outcome [1] 434571 0
Presence of agitated delirium
Timepoint [1] 434571 0
Recorded 6-hourly in the electronic medical record. Data will be recorded until 7 day or until the patient is discharged from ICU.
Secondary outcome [2] 434572 0
Lowest mean arterial pressure (MAP)
Timepoint [2] 434572 0
As recorded hourly in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [3] 434573 0
Lowest systolic blood pressure (SBP)
Timepoint [3] 434573 0
As recorded hourly in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [4] 434574 0
Lowest diastolic blood pressure (DBP)
Timepoint [4] 434574 0
As recorded hourly in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [5] 434575 0
Exposure to opioid medication
Timepoint [5] 434575 0
As recorded in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [6] 434576 0
Exposure to benzodiazepine medication
Timepoint [6] 434576 0
As recorded in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [7] 434577 0
Exposure to propofol medication
Timepoint [7] 434577 0
As recorded in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [8] 434578 0
Any adverse drug event related to the administration of guanfacine, for example fatigue and abdominal pain.
Timepoint [8] 434578 0
As recorded in the patient’s medical record until 7 days or patient discharge from ICU.
Secondary outcome [9] 434579 0
Any adverse drug event related to the administration of quetiapine, for example fatigue and abdominal pain.
Timepoint [9] 434579 0
As recorded in the patient’s medical record and occurring from the time of first study drug administration until 7 days or patient discharge from ICU.
Secondary outcome [10] 434580 0
ICU length of stay in days.
Timepoint [10] 434580 0
Upon discharge from ICU, hospital or death, whichever occur first.
Secondary outcome [11] 434581 0
Hospital length of stay in days
Timepoint [11] 434581 0
Upon discharge from ICU, hospital or death, whichever occur first.
Secondary outcome [12] 434582 0
ICU mortality censored at 28-days
Timepoint [12] 434582 0
Upon discharge from ICU, hospital or death, whichever occur first.
Secondary outcome [13] 434583 0
Hospital mortality censored at 28-days
Timepoint [13] 434583 0
Upon discharge from ICU, hospital or death, whichever occur first.

Eligibility
Key inclusion criteria
Adults aged equal to or older than 18 years
Admitted to the intensive care unit
Richmond Agitation Sedation Scale (RASS) score range of +1 to +4 points (agitation)
Physician has a plan to prescribe antipsychotic agent for treat agitation or delirium
The treating physician believed that guanfacine or quetiapine are equally appropriate for such treatment
• Likely to remain in the ICU until the day after tomorrow
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Admitted with a primary neurologic condition or injury, for example ischemic stroke, intracranial hemorrhage, active seizure
History of hepatic encephalopathy or end-stage liver disease defined as a Childs-Pugh class B or worse.
Previous diagnosis of psychiatric disorder or history of substance abuse
Actively withdrawing from alcohol intoxication and delirium tremens
Antipsychotic agent uses in the 10 days prior to Intensive care unit admission
Current treatment with dexmedetomidine or clonidine
Current treatment with an agent the potential to affect guanfacine or quetiapine concentrations that include cytochrome P450 subtype 3A4 inducer (e.g. phenobarbital, phenytoin, carbamazepine, rifampin) and 3A4 inhibitors (e.g. ketoconazole, voriconazole, clarithromycin)
Known allergy to guanfacine or quetiapine
Any contraindication to guanfacine or quetiapine includes borderline unsupported blood pressure defined by systolic blood pressure less than 90 mmHg or diastolic blood pressure less than 40 mmHg, heart rate less than 50 beats per minute, and baseline QTc interval greater than 500 milliseconds.
Renal impairment which defined by creatinine clearance less than 30 ml/min, calculate by Cockcroft-Gault equation
Suspected or confirmed pregnancy at time of assessment of eligibility

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer-generated permuted block
Masking / blinding
Who is / are masked / blinded?



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

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
1/09/2025
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
36
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 26955 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 43027 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 316415 0
Hospital
Name [1] 316415 0
Austin Health
Country [1] 316415 0
Australia
Primary sponsor type
Hospital
Name
Austin Hospital
Address
Country
Australia
Secondary sponsor category [1] 318583 0
None
Name [1] 318583 0
Address [1] 318583 0
Country [1] 318583 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315211 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 315211 0
Ethics committee country [1] 315211 0
Australia
Date submitted for ethics approval [1] 315211 0
30/04/2024
Approval date [1] 315211 0
15/08/2024
Ethics approval number [1] 315211 0
HREC/108664/Austin-2024

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 133990 0
Prof Rinaldo Bellomo
Address 133990 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 133990 0
Australia
Phone 133990 0
+61 394965992
Fax 133990 0
Email 133990 0
[email protected]
Contact person for public queries
Name 133991 0
Rinaldo Bellomo
Address 133991 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 133991 0
Australia
Phone 133991 0
+61 394965992
Fax 133991 0
Email 133991 0
[email protected]
Contact person for scientific queries
Name 133992 0
Rinaldo Bellomo
Address 133992 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 133992 0
Australia
Phone 133992 0
+61 394965992
Fax 133992 0
Email 133992 0
[email protected]

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 not sought for sharing of patient data


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
No additional documents have been identified.