Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001551785
Ethics application status
Approved
Date submitted
6/12/2022
Date registered
15/12/2022
Date last updated
1/12/2023
Date data sharing statement initially provided
15/12/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Fludrocortisone treatment in patients with aneurysmal sub arachnoid haemorrhage
Scientific title
Effect of treatment with fludrocortisone on the incidence of hyponatremia in patients with aneurysmal sub arachnoid haemorrhage: a pilot study
Secondary ID [1] 307399 0
Nil known
Universal Trial Number (UTN)
Trial acronym
FLASH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aneurysmal sub arachnoid haemorrhage 326731 0
Condition category
Condition code
Neurological 323967 323967 0 0
Other neurological disorders
Stroke 325512 325512 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Fludrocortisone 100µg tablet six hourly for fourteen days.
Intervention code [1] 323836 0
Prevention
Comparator / control treatment
Control group participants will receive standard care; ie no treatment to prevent hyponatraemia
Control group
Active

Outcomes
Primary outcome [1] 331762 0
Serum sodium concentrations
Timepoint [1] 331762 0
Fourteen days post enrolment
Secondary outcome [1] 411050 0
Incidence of hyponatremia (defined as two consecutive serum sodium concentrations below 135mmol/L at least six hours apart)
Timepoint [1] 411050 0
During ICU admission

Eligibility
Key inclusion criteria
1. Age 18 years or older
2. Diagnosed with aneurysmal subarachnoid haemorrhage (aSAH) from an aneurysm confirmed on computed tomography angiography (CTA) or digital subtraction angiography (DSA) of the intra-cranial arteries
3. Admitted to an Intensive Care or High Dependency Unit
4. Hospital admission for aneurysmal subarachnoid haemorrhage within 96 hours
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable to receive enteral medications
2. Pre-existing glucocorticoid or mineralocorticoid treatment (excluding inhaled)
3. Previous allergic reaction to fludrocortisone
4. Hospital admission for aSAH greater than 96 hours ago
5. History of cardiac, hepatic or renal failure
6. Hypernatraemia (Na>145mol/L) on the most recent blood sample at the time of screening.
7. Death deemed imminent or inevitable
8. Pregnancy (confirmed or suspected)
9. Documented systemic fungal infection
10. Previous enrolment in the trial

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)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
All analyses will be conducted on an intention to treat basis using standard statistical methods for categorical, count, continuous variables and time-to-event outcome data. Daily measures will be compared using repeated-measure linear mixed models. GAM models will be constructed using penalized regression splines and a thin plate smoother with each patient modelled as a random effect and with a fixed-effect covariates set including sex, age, hospital, WFNS severity, APACHE III score, time to intervention, method of securement, and sodium treatment methods.
The sample size will be fifty patients, based upon previous reports of fludrocortisone use and the high incidence of the use of sodium replacement therapies in this population

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2024
Actual
Date of last participant enrolment
Anticipated
1/06/2025
Actual
Date of last data collection
Anticipated
1/12/2025
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 23686 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 23687 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 23688 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 39123 0
2065 - St Leonards
Recruitment postcode(s) [2] 39124 0
3004 - Melbourne
Recruitment postcode(s) [3] 39122 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 311676 0
Charities/Societies/Foundations
Name [1] 311676 0
Princess Alexandra Hospital Foundation
Country [1] 311676 0
Australia
Primary sponsor type
Hospital
Name
Metro North Hospital and Health Service
Address
Level 14, Block 7
Royal Brisbane and Women's Hospital
HERSTON QLD 4029
Country
Australia
Secondary sponsor category [1] 314493 0
None
Name [1] 314493 0
Address [1] 314493 0
Country [1] 314493 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311131 0
Royal Brisbane and Women's Hospital
Ethics committee address [1] 311131 0
Royal Brisbane and Women's Hospital
Butterfield St, Herston QLD 4029
Ethics committee country [1] 311131 0
Australia
Date submitted for ethics approval [1] 311131 0
Approval date [1] 311131 0
12/08/2022
Ethics approval number [1] 311131 0
HREC/ 2022/MNHB/86268

Summary
Brief summary
Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating form of haemorrhagic stroke, that results from bleeding from an intracranial aneurysm. A common complication of aSAH is hyponatremia with a reported prevalence of between 35% to 77%.Our group has recently demonstrated that patients in whom the sodium concentration decreases over the ICU stay have a higher likelihood of a worse outcome at 6-months compared to those patients in whom the sodium concentration remains steady. Fludrocortisone is a synthetic adrenocortical steroid possessing activity which produces significant sodium and fluid retention. Previous studies of fludrocortisone have demonstrated a reduction in hyponatraemia and fluid loss, but these studies were underpowered to show a clinical outcome benefit. Fludrocortisone therefore has the potential to prevent the onset of hyponatraemia in aSAH and lead to improved outcomes; however, this has never been tested in an adequately designed trial. This proposal is for a Phase 2 trial to examine the effect of fludrocortisone administration on serum sodium concentrations, fluid balance and clinical outcomes measures in patients with aSAH.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 120050 0
A/Prof Jeremy Cohen
Address 120050 0
ICU Offices
Royal Brisbane and Women's Hospital
Butterfield St
Herston 4029
QLD
Country 120050 0
Australia
Phone 120050 0
+61 736388975
Fax 120050 0
Email 120050 0
jeremy.cohen@health.qld.gov.au
Contact person for public queries
Name 120051 0
A/Prof Jeremy Cohen
Address 120051 0
ICU Offices
Royal Brisbane and Women's Hospital
Butterfield St
Herston 4029
QLD
Country 120051 0
Australia
Phone 120051 0
+61 736388975
Fax 120051 0
Email 120051 0
jeremy.cohen@health.qld.gov.au
Contact person for scientific queries
Name 120052 0
A/Prof Jeremy Cohen
Address 120052 0
ICU Offices
Royal Brisbane and Women's Hospital
Butterfield St
Herston 4029
QLD
Country 120052 0
Australia
Phone 120052 0
+61 736388975
Fax 120052 0
Email 120052 0
jeremy.cohen@health.qld.gov.au

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.