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Trial registered on ANZCTR


Registration number
ACTRN12625000103460p
Ethics application status
Submitted, not yet approved
Date submitted
10/01/2025
Date registered
30/01/2025
Date last updated
30/01/2025
Date data sharing statement initially provided
30/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and feasibility of Intramuscular Dexmedetomidine for Delirium
Scientific title
Safety and feasibility of IntraMuscular DEXmedetomidine in reducing the incidence of delirium in at risk Intensive Care Unit patients: a pilot randomised trial
Secondary ID [1] 313679 0
None
Universal Trial Number (UTN)
U1111-1317-5395
Trial acronym
SIMDEX
Linked study record

Health condition
Health condition(s) or problem(s) studied:
critical illness
 336253 0
Delirium 336254 0
Condition category
Condition code
Neurological 332797 332797 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
• A daily dose of 1 mcg/kg dexmedetomidine (max of 100 mcg).
• Given intramuscularly in the deltoid or gluteal muscle between 7 – 9 pm
• Administered while in the ICU for up to a maximum of five days
Intervention code [1] 330272 0
Treatment: Drugs
Comparator / control treatment
• Usual clinician-dependent approach to the management of delirium risk.
• This may involve appropriate analgesic assessment and management, early mobility and exercise, family engagement, maximising sleep, preserving the day-night cycle where able.
• This may also involve the use or cessation of of sedative, neuroleptic or anaesthetic medication.
Control group
Active

Outcomes
Primary outcome [1] 340319 0
Significant Adverse Cardiovascular Event (ACE) (safety and Feasibility)
Timepoint [1] 340319 0
48h post each intramuscular dexmedetomidine dose delivery
Secondary outcome [1] 443700 0
Pharmacokinetics of Dexmedetomidine
Timepoint [1] 443700 0
1h, 4h, 9-12h post-administration each intra-muscular dose (last to coincide with routine blood tests)
Secondary outcome [2] 443703 0
Number of days alive and delirium free days to 14 days (this is a composite outcome)
Timepoint [2] 443703 0
Daily until D14 post-randomisation
Secondary outcome [3] 443704 0
Occurrence of delirium D1 post-IM DEXMED administration
Timepoint [3] 443704 0
24h post administration of first intra-muscular dose
Secondary outcome [4] 443961 0
Sleep architecture (% time awake, in REM, in Stage N1/2/3 Sleep)
Timepoint [4] 443961 0
Measured overnight until waking, Night 1, 2, 3 from initial randomisation.
Secondary outcome [5] 443967 0
Sleep efficiency
Timepoint [5] 443967 0
Measured overnight until waking, Night 1, 2, 3 from initial randomisation.
Secondary outcome [6] 443968 0
Randomised to screened patient ratio
Timepoint [6] 443968 0
Post-study completion
Secondary outcome [7] 443969 0
Number and nature of adverse events in each group
Timepoint [7] 443969 0
Unitl 48h after the administration of an intramuscular treatment dose of dexmedetomidine
Secondary outcome [8] 443971 0
Reasons for exclusions
Timepoint [8] 443971 0
Cumulative exclusion data will be assessed at the conclusion of the study.
Secondary outcome [9] 443972 0
Compliance with drug administration protocol
Timepoint [9] 443972 0
Daily totals on days intramuscular dexmedetomidine is administered.
Secondary outcome [10] 443973 0
Incidence of physical restraint use
Timepoint [10] 443973 0
Daily totals until ICU discharge.
Secondary outcome [11] 443974 0
Incidence and intensity of pharmacological therapy for delirium
Timepoint [11] 443974 0
Daily totals until ICU discharge.

Eligibility
Key inclusion criteria
Patients must satisfy ALL of the following inclusion criteria:
1. Aged 65 or older on the day of screening.
2. Expected to stay in ICU for longer than 24 hours.
3. Not receiving invasive mechanical ventilation
4. Arterial line in situ prior to the first dose of the drug to enable blood sampling
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria
Patients must not have ANY of the following exclusion criteria:
1. Any contraindication or allergy to dexmedetomidine
2. Patients admitted with any form of acute neurological disturbance
a. Suspected or proven acute primary brain injury
b. Acute encephalopathy or altered level of consciousness
c. Patients receiving therapy for delirium or agitation
d. Documented history of cognitive decline or dementia
e. Chronically receiving multiple antipsychotic medications
3. Haemodynamic Concerns, defined as:
a. Requiring significant vasopressor support
i. Norepinephrine > 0.2 mcg/kg/min or equivalent
b. Heart rate <50/min in the absence of a functioning pacemaker
c. Systolic blood pressure of < 100 mmHg with or without pressor support
4. Significant coagulopathy defined by either of:
a. Platelets of < 50,000
b. INR > 3
5. Acute fulminant hepatic failure
6. Pregnancy or active breastfeeding
7. Incipient mortality, or moribund patient likely to die within the next 48h
8. Undergoing active palliative care intervention at the end of life
9. Unable to receive intramuscular injections for any reason
10. Enrolled in other trials of dexmedetomidine
11. Previously enrolled in this study
12. Any other relevant significant clinical reason identified by the treating team

Study design
Purpose of the study
Prevention
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)
A permuted block randomisation with stratification by study site, age (65-75, 75-85, >85), the presence or absence of frailty (Clinical Frailty Score >4) and admitting diagnosis (surgical vs medical) will be used.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety
Statistical methods / analysis
Summary statistics will be used to describe the clinical data and presented as mean ± SD, median with interquartile range or percentages as appropriate. Chi-squared analysis (with Fisher’s exact test if appropriate), Student’s t-test or the Mann Whitney U test, or linear regression will be used to compare data between the intervention and usual care groups. Statistical significance declared for probability values of < 0.05. There will be no imputation for missing data.

Qualitative and quantitative analyses will be performed to assess the primary outcome of feasibility. Variable Free Day outcomes will be undertaken as time-to-event analyses using a competing risks regression framework, with death as a competing event. If no deaths are observed, then analysis will revert to Cox proportional hazards regression. The group estimates will be presented as the respective sub-hazard (or hazard) ratios with associated 95% confidence intervals (95%CI), and presented as the respective cumulative incidence rates as per Fine & Gray. A secondary analysis will be adjusted for age and frailty. Length of ICU stay will be analysed similarly as days alive and ICU-free at day 14, with deaths assigned zero.

Pre-specified subgroup analyses will include age (65-75, 75-85, >85); frailty (CFS <4 or = 4); sepsis (yes/no); surgical admission (yes/no); severity of illness (APACHE II < 25 vs. = 25). The analyses for the heterogeneity of effects across subgroups will use a treatment × subgroup interaction term added to the logistic regression described above.

Baseline covariates will be presented as number (%), median [interquartile range, IQR], or mean (standard deviation, SD); between group differences will be analysed by chi-squared, Kruskal-Wallis test or linear regression.

Plasma concentration-time curves for dexmedetomidine will be presented as mean profiles with corresponding 95%CI.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/04/2025
Actual
Date of last participant enrolment
Anticipated
6/04/2026
Actual
Date of last data collection
Anticipated
31/05/2026
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27459 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [2] 27460 0
Dandenong Hospital- Monash Health - Dandenong
Recruitment hospital [3] 27461 0
Victorian Heart Hospital - Clayton
Recruitment hospital [4] 27462 0
Casey Hospital - Berwick
Recruitment postcode(s) [1] 43571 0
3168 - Clayton
Recruitment postcode(s) [2] 43572 0
3175 - Dandenong
Recruitment postcode(s) [3] 43573 0
3806 - Berwick

Funding & Sponsors
Funding source category [1] 318142 0
Hospital
Name [1] 318142 0
Intensive Care Unit Institutional Funding, Monash Health
Country [1] 318142 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Country
Australia
Secondary sponsor category [1] 320588 0
None
Name [1] 320588 0
Address [1] 320588 0
Country [1] 320588 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316788 0
Monash Health Human Research Ethics Committee A
Ethics committee address [1] 316788 0
https://monashhealth.org/research/resources/resource-library/
Ethics committee country [1] 316788 0
Australia
Date submitted for ethics approval [1] 316788 0
05/09/2024
Approval date [1] 316788 0
Ethics approval number [1] 316788 0

Summary
Brief summary
This is a pilot feasibility randomized clinical trial comparing the novel intramuscular use of dexmedetomidine, an alpha-2 agonist agent, in preventing delirium and improving sleep in older, non-ventilated intensive care patients, compared with usual care. The main aims are to determine if using the drug in this context is safe, and if further, larger studies would be feasible.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 139014 0
Dr Adrian Pakavakis
Address 139014 0
Department of Intensive Care, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168
Country 139014 0
Australia
Phone 139014 0
+61 03 9594 3277
Fax 139014 0
Email 139014 0
[email protected]
Contact person for public queries
Name 139015 0
Ms Alice Li
Address 139015 0
Department of Intensive Care, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168
Country 139015 0
Australia
Phone 139015 0
+61 03 9594 3196
Fax 139015 0
Email 139015 0
[email protected]
Contact person for scientific queries
Name 139016 0
A/Prof Neil Glassford
Address 139016 0
Department of Intensive Care, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168
Country 139016 0
Australia
Phone 139016 0
+61 03 9594 3277
Fax 139016 0
Email 139016 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


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.