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Trial registered on ANZCTR


Registration number
ACTRN12617001540303
Ethics application status
Approved
Date submitted
30/10/2017
Date registered
7/11/2017
Date last updated
4/12/2018
Date data sharing statement initially provided
4/12/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Steroids To Reduce the Impact on DElirium study (STRIDE)
Scientific title
Steroids To Reduce the Impact on DElirium (STRIDE) study - pilot randomised controlled trial of preoperative dexamethasone to prevent delirium after hip fracture.
Secondary ID [1] 293218 0
Nil known
Universal Trial Number (UTN)
U1111-1194-9950
Trial acronym
STRIDE
Linked study record
N/A

Health condition
Health condition(s) or problem(s) studied:
Delirium 305231 0
Hip Fracture 305232 0
Condition category
Condition code
Anaesthesiology 304535 304535 0 0
Anaesthetics
Surgery 304536 304536 0 0
Other surgery
Injuries and Accidents 304537 304537 0 0
Fractures

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Dexamethasone (20mg) intravenous infusion delivered once (as early as possible after acute admission to hospital)
Intervention code [1] 299475 0
Prevention
Intervention code [2] 299531 0
Treatment: Drugs
Comparator / control treatment
Placebo (sodium chloride 0.9%)
Control group
Placebo

Outcomes
Primary outcome [1] 303773 0
Delirium incidence assessed by the 4A'S test (4AT)
Timepoint [1] 303773 0
Postoperative day 1, 2 and 3
Primary outcome [2] 303774 0
Delirium severity assessed by the Memorial Delirium Assessment Scale (MDAS)
Timepoint [2] 303774 0
Postoperative day 1, 2 and 3 (if delirium is developed on any of these days, MDAS will be assessed daily until it resolves, or until discharged from the orthopaedic ward.
Primary outcome [3] 303816 0
Feasibility issue; participant eligibility
Timepoint [3] 303816 0
Monthly
Secondary outcome [1] 340215 0
Primary outcome; feasibility issue; participant accrual for the trial
Timepoint [1] 340215 0
Monthly
Secondary outcome [2] 340216 0
Primary outcome; feasibility issue; timing of the intervention (how early after admission we are able to deliver the intervention)
Timepoint [2] 340216 0
Monthly
Secondary outcome [3] 340217 0
Primary outcome; feasibility issue; safety
Timepoint [3] 340217 0
Adverse events will be reviewed individually in real-time and in aggregate on a weekly basis. Interim analyses of safety data by independent data monitoring committee after 10, 40 and 80 patients have been enrolled.
Secondary outcome [4] 340218 0
Levels of inflammatory cytokines in blood and cerebrospinal fluid. These samples will be analysed for cytokines and biomarkers previously associated with delirium (S100B, IL-1B, IL-2, IL-6, IL-8, IL-10, IL-13, TNFa, IL-1RA, IFNy, IGF-1, and Cortisol).
Timepoint [4] 340218 0
Blood samples (baseline, day of surgery, postoperative day 1, 2 and 3.
CSF sample (at time of surgery).
Secondary outcome [5] 340297 0
Acute postoperative pain will be assessed with the Numerical Rating Scale (NRS 0-10)
Timepoint [5] 340297 0
Postoperative day 1, 2 and 3
Secondary outcome [6] 340298 0
Length of hospital stay
Timepoint [6] 340298 0
At discharge from hospital
Secondary outcome [7] 340299 0
Mortality rates
Timepoint [7] 340299 0
30 days and 12 months

Eligibility
Key inclusion criteria
65 years and older
Fractured neck of femur

Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Dementia or any cognitive deficit
Delirium on admission
Used steroids in the last 7 days
Significant and poorly controlled diabetes (glucose >12 mmol/l on admission)
Systemic infection
Unable to read and speak English

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)
The researcher recruiting patients to the study is blinded to the allocation. Allocation involves contacting the holder of the allocation schedule who is "off-site".
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation
Stratification by age (65-79, 80-89, >90)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving 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)
Safety/efficacy
Statistical methods / analysis
Because this is a pilot trial, the sample size is not designed to achieve adequate power to observe statistically significant results. Rather, the aim is to assess feasibility issues such as participant accrual for the trial, drug safety, and provide effect size estimates for the effects of dexamethasone on POD incidence, severity and duration. A sample size of 120 participants is the largest sample size that is feasible to recruit from our hospital in a 12-18 month period. The largest feasible sample size has been chosen, as this will provide greater precision in the estimates of both efficacy and safety to inform a larger study.

Quantitative data will be summarised using descriptive statistics with analyses primarily focused on confidence interval and effect size estimation, rather than formal hypothesis testing.
Participant eligibility and recruitment: A screening log will be kept documenting the number of patients screened, ineligible, eligible, consented and declined. We will describe 1) the proportion of screened patients who meet the inclusion criteria and 2) the consent rate of eligible patients.
Timing of the intervention: A log will be kept of the time the intervention is delivered. This will be compared to the hospital admission time and we will describe the time from hospital admission to delivery of the intervention.
Appropriate dosing: The change in serum inflammatory biomarkers from baseline (pre-intervention) to postoperative days 1, 2 and 3 will be described and compared between groups to estimate the magnitude and duration of the immune modulating effect of dexamethasone 20mg in this population. Where appropriate, inferential statistics may be utilised. The relationships between biomarker levels and POD incidence and severity will also be explored.
Drug safety: The number and type of adverse events will be described in the dexamethasone and placebo groups. Rates of adverse events in the dexamethasone and placebo groups will be compared. and expressed as relative risk ratios with 95% confidence intervals with a relative risk greater than 1.0 indicating a harmful effect of dexamethasone.
Effect size: The incidence of POD is considered a binary outcome (greater than or equal to 4 on 4AT on any postoperative day). The results will be expressed as relative risk ratios with 95% confidence intervals for the dexamethasone group relative to the placebo group, with a relative risk less than 1.0 indicating a beneficial effect. The duration of delirium will be taken as the number of consecutive days with a 4AT score greater than or equal to 4 from its earliest occurrence, described in each group and compared between the dexamethasone and placebo groups using effect size estimates. The severity of delirium will be characterized by the highest value of the MDAS during an episode with delirium, described in each group and compared between the dexamethasone and placebo groups using effect size estimates. Secondary outcomes (acute postoperative pain, mortality rates, length of stay) will be described and compared between the dexamethasone and placebo groups using effect size estimates.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 9328 0
New Zealand
State/province [1] 9328 0
Auckland

Funding & Sponsors
Funding source category [1] 297845 0
Hospital
Name [1] 297845 0
Waitemata District Health Board
Address [1] 297845 0
North Shore Hospital
Private Bag 93503
North Shore, Auckland 0740
Country [1] 297845 0
New Zealand
Funding source category [2] 301362 0
Government body
Name [2] 301362 0
Health Research Council of New Zealand (HRC)
Address [2] 301362 0
Health Research Council of New Zealand
PO Box 5541, Wellesley Street, Auckland 1141
Country [2] 301362 0
New Zealand
Primary sponsor type
Hospital
Name
Waitemata District Health Board
Address
North Shore Hospital
Private Bag 93503
North Shore, Auckland 0740
Country
New Zealand
Secondary sponsor category [1] 296885 0
None
Name [1] 296885 0
Address [1] 296885 0
Country [1] 296885 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298891 0
Health and Desability Ethics Committees
Ethics committee address [1] 298891 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 298891 0
New Zealand
Date submitted for ethics approval [1] 298891 0
25/05/2017
Approval date [1] 298891 0
07/07/2017
Ethics approval number [1] 298891 0
17/NTB/98

Summary
Brief summary
Postoperative delirium (POD) is an important clinical problem commonly observed in elderly patients during the first few days following hip fracture surgery. POD is associated with increased length of hospital stay and significantly higher morbidity and mortality rates than those who do not get POD. The reported incidence of POD in patients following hip fracture surgeries varies between 16% and 62%. Studies suggest that inflammation related to the stress response from the initial trauma (the fracture itself) as well as from the surgical procedure (the operation), are important contributing factors that lead to neuro-inflammation, cognitive dysfunction and POD. Thus, it is possible that exogenous steroids, which reduce inflammation, can reduce the risk of developing POD. Dexamethasone (corticosteroid) has been shown to reduce the release of inflammatory markers after surgery. However, there have been no clinical studies to confirm the potential efficacy and safety of dexamethasone at preventing POD in this specific population. Furthermore, there are unique feasibility issues in conducting such a study in this population.

The main aims with this feasibility study are to assess the safety and feasibility of systemic dexamethasone, administered as early as possible after arrival to hospital, in patients with hip fractures, to determine whether a large multi-centre randomised controlled trial should be conducted. Provided acceptable safety and feasibility can be demonstrated, results of the feasibility study will be used to estimate important parameters that are needed to inform the design of a larger multi-centre phase III clinical trial. The main aim of the full study is to investigate the effectiveness of dexamethasone on decreasing incidence, severity and duration of POD. Secondary outcomes include levels of inflammatory cytokines in blood and cerebrospinal fluid.

This randomised, placebo-controlled, double-blind clinical trial will include 120 patients aged 65 and over admitted for hip fracture. Patients will be randomised to receive either dexamethasone 20 mg or placebo. To examine safety, drug related complications will be compared between the intervention and control group. Further feasibility issues (e.g. generating a robust estimate of the potential effect size, a sustainable recruitment rate, the real world incidence in our population etc.) will be assessed. POD incidence and duration will be assessed with the 4A’s test (4AT), on postoperative day 1, 2 and 3. Patients who develop POD during any of these days will be assessed daily until it resolves, or until discharged from the orthopaedic ward. Severity of POD will be assessed with the Memorial Delirium Assessment Scale (MDAS). The inflammatory response will be assessed in a sub sample of patients by collecting blood samples and one cerebrospinal fluid (CSF) sample. These samples will be analysed for cytokines and biomarkers previously associated with delirium.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78582 0
Dr Michal Kluger
Address 78582 0
Waitemata District Health Board
North Shore Hospital
Department of Anaesthesia and Perioperative medicine
Private Bag 93-503
North Shore City, Auckland 0740
Country 78582 0
New Zealand
Phone 78582 0
+64 21 684022
Fax 78582 0
Email 78582 0
michal.kluger@waitematadhb.govt.nz
Contact person for public queries
Name 78583 0
Dr Michal Kluger
Address 78583 0
Waitemata District Health Board
North Shore Hospital
Department of Anaesthesia and Perioperative medicine
Private Bag 93-503
North Shore City, Auckland 0740
Country 78583 0
New Zealand
Phone 78583 0
+64 21 684022
Fax 78583 0
Email 78583 0
michal.kluger@waitematadhb.govt.nz
Contact person for scientific queries
Name 78584 0
Dr Michal Kluger
Address 78584 0
Waitemata District Health Board
North Shore Hospital
Department of Anaesthesia and Perioperative medicine
Private Bag 93-503
North Shore City, Auckland 0740
Country 78584 0
New Zealand
Phone 78584 0
+64 21 684022
Fax 78584 0
Email 78584 0
michal.kluger@waitematadhb.govt.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Not applicable