Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000368437
Ethics application status
Approved
Date submitted
16/04/2025
Date registered
28/04/2025
Date last updated
28/04/2025
Date data sharing statement initially provided
28/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Intranasal insulin for prevention of perioperative delirium in femoral fracture surgery
Scientific title
A phase II single site, triple blind randomised placebo-controlled trial of short-acting intranasal insulin for the prevention of delirium in older patients undergoing surgery for femoral fracture
Secondary ID [1] 314162 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Delirium 336996 0
Condition category
Condition code
Neurological 333463 333463 0 0
Other neurological disorders
Surgery 333628 333628 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nebulised intranasal insulin.

Drug: insulin aspart.
Dose: 30 international units (0.3mL) twice daily.
Device: Nasal drug delivery device (Teleflex MAD NasalTM Intranasal Mucosal Atomization Device).

Administration: Administration to a nostril twice daily (morning and evening) assisted by registered nurse.
Duration: Commence treatment on enrolment until day 3 post-surgery.
Monitoring adherence: Ward nurses will undergo training in preparation for the trial to ensure adherence to the trial protocol as well as consistent drug administration and documentation. Missed doses and tolerability will be documented by the nurses on electronic medical records and this will be reviewed by the study team.
Intervention code [1] 330762 0
Treatment: Drugs
Comparator / control treatment
Diluent placebo

Drug: Diluent (glycerin 16 mg, metacresol 1.6 mg, phenol 0.65 mg and sodium phosphate dibasic 3.8 mg dissolved in 1 ml distilled water)
Dose: 0.3mL twice daily.
Device: Nasal drug delivery device (Teleflex MAD NasalTM Intranasal Mucosal Atomization Device).

Administration: Administration to a nostril twice daily (morning and evening) assisted by registered nurse.
Duration: Commence treatment on enrolment until day 3 post-surgery.
Monitoring adherence: Ward nurses will undergo training in preparation for the trial to ensure adherence to the trial protocol as well as consistent drug administration and documentation. Missed doses and tolerability will be documented by the nurses on electronic medical records and this will be reviewed by the study team.
Control group
Placebo

Outcomes
Primary outcome [1] 341035 0
Incidence of delirium.
Timepoint [1] 341035 0
Daily assessment will be conducted from admission until day 4 postoperatively.
Secondary outcome [1] 445885 0
Duration of delirium.
Timepoint [1] 445885 0
Daily assessment until day 4 postoperatively. If delirium is present and persists on day 4 postoperatively, then assessment will be continued at least five times per week until delirium resolves, transfer to other hospital or hospital discharge.
Secondary outcome [2] 445886 0
Severity of delirium.
Timepoint [2] 445886 0
Daily assessment until day 4 postoperatively. If delirium is present and persists on day 4 postoperatively, the assessment will be continued at least five times per week until delirium resolves, transfer to other hospital or hospital discharge.
Secondary outcome [3] 445891 0
Acute and total length of hospital stay.
Timepoint [3] 445891 0
At discharge from hospital.
Secondary outcome [4] 445893 0
Hospital-acquired complications.
Timepoint [4] 445893 0
At discharge from hospital.
Secondary outcome [5] 445895 0
New admission to a residential aged care facility.
Timepoint [5] 445895 0
At discharge from hospital, at 4 month telephone follow up and at 12 months follow up.
Secondary outcome [6] 445896 0
Incidence of cognitive decline at 12 months follow up (from admission).
Timepoint [6] 445896 0
On admission (MMSE) and at 12 months (ACE-R) follow up.
Secondary outcome [7] 445897 0
New onset dementia at 12 months follow up (from admission).
Timepoint [7] 445897 0
On admission (MMSE) and at 12 months (ACE-R) follow up.
Secondary outcome [8] 445898 0
Mortality rates.
Timepoint [8] 445898 0
During admission, at 4 month telephone follow up and at 12 months follow up.
Secondary outcome [9] 445899 0
Preserved activities of daily living at 12 months from baseline.
Timepoint [9] 445899 0
At 12 months follow up.
Secondary outcome [10] 445900 0
Health care utilisation and cost of care.
Timepoint [10] 445900 0
At 4 and 12 months follow-up.
Secondary outcome [11] 445901 0
Quality of Life.
Timepoint [11] 445901 0
At 4 month telephone follow-up and at 12 months follow up.
Secondary outcome [12] 445902 0
Patients and caregiver emotional distress.
Timepoint [12] 445902 0
At Discharge.
Secondary outcome [13] 445903 0
Depression.
Timepoint [13] 445903 0
At 12 months follow up.

Eligibility
Key inclusion criteria
Aged 75 years or older, or aged 65-74 years with pre-existing cognitive impairment and/or frailty (clinical frailty scale (CFS) >4).
Undergoing orthopaedic surgery for femoral fractures (neck of femur, femoral shaft, distal femur and periprosthetic fractures of the femur).
Receiving inpatient care at the Prince of Wales Hospital.
Informed consent obtained.
Minimum age
65 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Prevalent delirium on admission to hospital diagnosed by a geriatrician or advanced trainee in geriatric medicine using the DSM-V criteria.
Expected prognosis is less than 7 days lifespan assessed by admitting medical consultant opinion.
Allergy to insulin formulation.
A structural abnormality precluding the use of nasal drug delivery device.
Unable to participate in cognitive testing and unable to establish whether the participant is at their neurocognitive baseline (i.e. at baseline cognition and function if pre-existing cognitive impairment) according to available sources of evidence (e.g. corroborative history from carer in addition to staff assessment on patient’s interaction, level of consciousness and fluctuations).
Participant objects to treatment.

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)
Allocation will be undertaken by staff in the hospital pharmacy as per the randomisation schedule.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be conducted using randomly permuted block randomisation with variable block sizes of 4-8 using a computer algorithm.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
Power analysis (with 5% significance and 80% power) was performed using Australian Hip Fracture Registry data for delirium rates in this population. A total of 216 participants will be required based on reducing incidence of post-operative delirium by 50% (from 34% to 17%) and allowing for a 5% dropout rate.
A statistical analysis plan will be developed and signed by the investigators prior to study completion and published in Open Science Framework (OSF). The primary analysis will be undertaken by researchers blind to group allocation.
An intention-to-treat approach will be adopted for all analyses and statistical significance assumed at the level of 5% (P<0.05). A Poisson or negative binomial regression will be used to test the differences in delirium incidence as well as hospital acquired complications between the arms depending on the distribution. The primary analysis will be replicated by another member of the research team or a statistician. Baseline characteristics will be reported for the overall population and separately for each group.
For descriptive statistics, continuous variables will be reported as mean with standard deviation or median and interquartile range, depending on their distribution. For between group comparisons, Student’s t-test and Mann-Whitney U tests will be adopted for normally and non-normally distributed data, respectively. Categorical/binary variables will be presented as frequency and percentages and will be analysed using the chi-squared or Fisher’s exact test. Depending on adherence, a per protocol analysis may be undertaken.
A priori subgroup analysis will be performed on the primary and secondary outcomes for the following groups:
• Baseline CFS
• History of cognitive impairment
• Baseline residential status
• Use of central nervous system medications at the point of admission
• Baseline functional independence
• Baseline ASA grade
• Adherence to treatment
• Depth of sedation
• Type and/or duration of anaesthesia (general vs regional anaesthetics)
• Anaesthetic agents
• Pre-existing comorbidities/CCI
• APOE4 status

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
28/04/2025
Actual
Date of last participant enrolment
Anticipated
27/04/2029
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
216
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 27730 0
Prince of Wales Hospital - Randwick
Recruitment postcode(s) [1] 43919 0
2031 - Randwick

Funding & Sponsors
Funding source category [1] 318674 0
Charities/Societies/Foundations
Name [1] 318674 0
The Julia Lowy Foundation
Country [1] 318674 0
Australia
Funding source category [2] 318677 0
Charities/Societies/Foundations
Name [2] 318677 0
Prince of Wales Hospital Foundation
Country [2] 318677 0
Australia
Primary sponsor type
Individual
Name
Prof Gideon A Caplan, The Prince of Wales Hospital
Address
Country
Australia
Secondary sponsor category [1] 321102 0
None
Name [1] 321102 0
Address [1] 321102 0
Country [1] 321102 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317287 0
South Eastern Sydney Local Health District HREC
Ethics committee address [1] 317287 0
Ethics committee country [1] 317287 0
Australia
Date submitted for ethics approval [1] 317287 0
09/01/2024
Approval date [1] 317287 0
29/02/2024
Ethics approval number [1] 317287 0
2024/ETH00005

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

Contacts
Principal investigator
Name 140574 0
Prof Gideon A Caplan
Address 140574 0
Department of Geriatric Medicine South Wing Edmund Blackett Building The Prince of Wales Hospital Barker Street Randwick NSW 2031
Country 140574 0
Australia
Phone 140574 0
+61293824252
Fax 140574 0
Email 140574 0
[email protected]
Contact person for public queries
Name 140575 0
Gideon A Caplan
Address 140575 0
Department of Geriatric Medicine South Wing Edmund Blackett Building The Prince of Wales Hospital Barker Street Randwick NSW 2031
Country 140575 0
Australia
Phone 140575 0
+61293824252
Fax 140575 0
Email 140575 0
[email protected]
Contact person for scientific queries
Name 140576 0
Gideon A Caplan
Address 140576 0
Department of Geriatric Medicine South Wing Edmund Blackett Building The Prince of Wales Hospital Barker Street Randwick NSW 2031
Country 140576 0
Australia
Phone 140576 0
+61293824252
Fax 140576 0
Email 140576 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• All de-identified individual participant data
What types of analyses could be done with individual participant data?
• Any type of analysis (i.e. no restrictions on data re-use)
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
No


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.