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Trial registered on ANZCTR


Registration number
ACTRN12621001016820
Ethics application status
Approved
Date submitted
2/06/2021
Date registered
4/08/2021
Date last updated
11/07/2022
Date data sharing statement initially provided
4/08/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of fluid restriction on incidence of delayed hyponatraemia post pituitary surgery
Scientific title
A randomised trial of the effect of prophylactic fluid restriction on the incidence of delayed hyponatraemia following pituitary surgery in adults
Secondary ID [1] 304388 0
nil known
Universal Trial Number (UTN)
nil
Trial acronym
nil
Linked study record
nil

Health condition
Health condition(s) or problem(s) studied:
Diabetes insipidus 322182 0
Condition category
Condition code
Metabolic and Endocrine 319873 319873 0 0
Other endocrine disorders
Surgery 320378 320378 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study will investigate the effectiveness of a fluid restriction (1L/day between days 4-9 post-pituitary surgery) to reduce the incidence of delayed hyponatraemia from syndrome of inappropriate antidiuretic hormone (SIADH), which typically occurs between days 7-10 following pituitary surgery.
Participants in both groups will be asked to keep a fluid balance record during this time, which will be used to assess adherence. Participants are usually discharged from hospital by day 4 post-operatively, therefore most participants will be at home during the time of the intervention.
Intervention code [1] 320749 0
Prevention
Comparator / control treatment
Participants randomised to usual care, will not be advised of the prophylactic fluid restriction (1L/24 hours). Usual care of these patients is no fluid restriction unless there is development of SIADH.
Control group
Active

Outcomes
Primary outcome [1] 327746 0
1. Percent of patients developing delayed hyponatraemia/SIADH within 30 days of surgery. Defined by: SIADH occurring days 4-11 post pituitary surgery with serum sodium < 134 mEq/l and low serum osmolality (<275 mOsm/l), euvolemic status, and normal renal, thyroid and adrenal function (and/or pituitary hormone replacement).
Participants blood tests results will be reviewed to assess the occurrence of hyponatremia post-pituitary surgery.
Timepoint [1] 327746 0
Delayed hyponatraemia from SIADH following pituitary surgery occurs within the first month of surgery. The time point therefore will be 1 month post-pituitary surgery for each participant.
Secondary outcome [1] 396409 0
1. Readmission for hyponatraemia within 14 days post-op. Criteria for readmission will include: symptomatic hyponatraemia and/or plasma sodium <129 mmol/L or ED presentation with hyponatraemia.
Participant medical records will be reviewed to assess for this outcome.
Timepoint [1] 396409 0
14 days post-pituitary surgery
Secondary outcome [2] 396410 0
2. Plasma sodium levels post-operatively day 7-11 (or until SIADH develops)
Timepoint [2] 396410 0
Day 11 post-pituitary surgery
Blood tests will be performed on day 7/8, 9/10 +/- 11 post-operatively for plasma sodium as per usual clinical care of these patients. The outcome will be assess using these blood test results.
Secondary outcome [3] 396411 0
3. Adverse effects: thirst (per thirst scale), serum creatinine and serum urea, >25% rise in serum creatinine (until day 11 or until SIADH occurs)
Serum creatinine and serum urea and thirst scale will be reviewed to assess for this outcome.
Timepoint [3] 396411 0
day 11 post-pituitary surgery
Secondary outcome [4] 396412 0
4. Tolerability, including adherence to prophylactic fluid restriction (until day 11 or until SIADH occurs)
The fluid balance record will be used to assess for adherence and tolerability to the fluid restriction.
Timepoint [4] 396412 0
Day 11 post-pituitary surgery
Secondary outcome [5] 396414 0
6. Compare kidney function (creatinine) between baseline and day 9 in FR group
Timepoint [5] 396414 0
Day 11 post-pituitary surgery
This outcome will be assess by comparing baseline kidney function to kidney function after fluid restriction (day 9 blood tests).
Secondary outcome [6] 399063 0
Compare kidney function ( urea) between baseline and day 9 in FR group
Timepoint [6] 399063 0
Day 11 post-pituitary surgery
This outcome will be assess by comparing baseline kidney function to kidney function after fluid restriction (day 9 blood tests).

Eligibility
Key inclusion criteria
1. Undergoing pituitary surgery
2. Pituitary tumour (functional and non-functional pituitary adenomas, Rathke’s cleft cyst, craniopharyngioma, other)
3. Adults 18 years of age or older
4. Willingness and able to give written or oral informed consent and willingness to participate to and comply with the study.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Women lactating, pregnant or of childbearing potential who are not willing to avoid becoming pregnant during the study, as pregnancy may interfere with the results of the study, and this group would make up an extremely small number of patients undergoing pituitary surgery.
• Participants with a history of a psychological illness or condition such as to interfere with the participant’s ability to understand the requirements of the study.
• Participants with diabetes mellitus and significant hyperglycaemia postoperatively (blood glucose levels greater than 12 mmol/L) or who have other causes of osmotic diuresis.
• The following medication(s) can have interactive effects and may interfere with the participants ability to meet the study requirements; they cannot be administered during the clinical study:
o Diuretic medications, mannitol, medications known to affect plasma sodium (including SSRIs, TCAs, anti-epileptics medications)
• Any patient with a pre-existing diagnosis of DI, or those requiring DDAVP on discharge (usually around day 4 post-op), or other medical condition where fluid restriction would be considered dangerous.

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)
On day 4 post-pituitary surgery, participants will undergo randomisation via computer generation to either fluid restriction or control group.
Computer allocation will be performed at each site to ensure randomisation is stratified to site.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
1:1 randomisation
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A calculated sample size of 68 participants, assuming approximately 20% prevalence of SIADH at our institution, would be required to provide 80% power (confidence level 95% and standard error 0.05). Allowing for dropout, the target sample size is 80 participants (40 participants per group).
Patient demographics, hospital course, pathology diagnosis, post-operative complications, post- operative SIADH, readmissions for hyponatraemia, postoperative plasma sodium levels, tolerability and adherence to prophylactic fluid restriction, and complications from fluid restriction will be evaluated.
Patient and clinical characteristics will be summarised using mean and standard deviation or median and interquartile range or frequency and percentage. These will be stratified by treatment group and compared using the independent sample t-test, Wilcoxon rank-sum test, Fisher’s exact test, or the chi-square test. Statistical comparisons between the control group and intervention group will be performed using Pearsons test of Fisher’s Exact test to evaluate differences in outcomes. For all tests, p< 0.05 will be considered statistically significant.
Statistical programs will be used in analysis and preparation of the results. For example, SPSS Statistical Software for analysis of descriptive statistics, and figures will be made using GraphPad Prism.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
30/08/2021
Actual
30/10/2021
Date of last participant enrolment
Anticipated
1/06/2023
Actual
Date of last data collection
Anticipated
1/07/2023
Actual
Sample size
Target
80
Accrual to date
20
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 19610 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [2] 19611 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [3] 19612 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [4] 19613 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [5] 19614 0
St Vincent's Hospital (Darlinghurst) - Darlinghurst
Recruitment hospital [6] 19615 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment hospital [7] 19616 0
St Vincent's Private Hospital - Fitzroy
Recruitment postcode(s) [1] 34246 0
4102 - Woolloongabba
Recruitment postcode(s) [2] 34247 0
4029 - Herston
Recruitment postcode(s) [3] 34248 0
4120 - Greenslopes
Recruitment postcode(s) [4] 34249 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 34250 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 308759 0
Self funded/Unfunded
Name [1] 308759 0
Emily Brooks
Country [1] 308759 0
Australia
Primary sponsor type
Hospital
Name
Princess Alexandra hospital
Address
Princess Alexandra Hospital
199 Ipswich Road
Woo4loongabba, 4102
Brisbane
Queensland
Australia
Country
Australia
Secondary sponsor category [1] 309661 0
None
Name [1] 309661 0
Address [1] 309661 0
Country [1] 309661 0
Other collaborator category [1] 281828 0
Individual
Name [1] 281828 0
Warrick Inder
Address [1] 281828 0
Department of Diabetes and Endocrinology
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Queensland, 4102
Australia
Country [1] 281828 0
Australia
Other collaborator category [2] 281833 0
Individual
Name [2] 281833 0
Christina Jang
Address [2] 281833 0
Department of Diabetes and Endocrinology
Royal Brisbane and Womens' Hospital
Butterfield St,
Herston
Queensland, 4029

Greenslopes Private Hospital
Newdegate St
Greenslopes
Queensland, 4120
Country [2] 281833 0
Australia
Other collaborator category [3] 281838 0
Individual
Name [3] 281838 0
Viral Chikani
Address [3] 281838 0
Department of Diabetes and Endocrinology
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Queensland, 4102
Australia

Greenslopes Private Hospital
Newdegate St
Greenslopes
Queensland, 4120
Country [3] 281838 0
Australia
Other collaborator category [4] 281839 0
Individual
Name [4] 281839 0
Carmela Caputo
Address [4] 281839 0
St Vincent's Private Hospital, Melbourne
159 Grey St
East Melbourne
Victoria, 3002
Country [4] 281839 0
Australia
Other collaborator category [5] 281840 0
Individual
Name [5] 281840 0
Ann McCormack
Address [5] 281840 0
St Vincent's Hospital, Sydney
390 Victoria St
Darlinghurst
NSW, 2010
Country [5] 281840 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308675 0
St Vincent's Hospital, Sydney
Ethics committee address [1] 308675 0
Ethics committee country [1] 308675 0
Australia
Date submitted for ethics approval [1] 308675 0
Approval date [1] 308675 0
12/05/2021
Ethics approval number [1] 308675 0

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

Contacts
Principal investigator
Name 111518 0
Dr Emily Brooks
Address 111518 0
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Brisbane
QLD, 4102
Country 111518 0
Australia
Phone 111518 0
+610731769562
Fax 111518 0
Email 111518 0
emily.brooks@health.qld.gov.au
Contact person for public queries
Name 111519 0
Emily Brooks
Address 111519 0
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Brisbane
QLD, 4102
Country 111519 0
Australia
Phone 111519 0
+610731761111
Fax 111519 0
Email 111519 0
emily.brooks@health.qld.gov.au
Contact person for scientific queries
Name 111520 0
Emily Brooks
Address 111520 0
Princess Alexandra Hospital
199 Ipswich Road
Woolloongabba
Brisbane
QLD, 4102
Country 111520 0
Australia
Phone 111520 0
+610731769562
Fax 111520 0
Email 111520 0
emily.brooks@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.