Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621000587808
Ethics application status
Approved
Date submitted
1/03/2020
Date registered
18/05/2021
Date last updated
21/04/2022
Date data sharing statement initially provided
18/05/2021
Date results information initially provided
21/04/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Salt and water balance in children with appendicitis
Scientific title
Sodium and Water homeostasis in children admitted with acute appendicitis: an observational prospective fluid balance cohort study
Secondary ID [1] 300683 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Appendicitis 316492 0
Dehydration 316493 0
Condition category
Condition code
Surgery 314740 314740 0 0
Other surgery
Oral and Gastrointestinal 317172 317172 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Metabolic and Endocrine 317173 317173 0 0
Other metabolic disorders

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This cohort study that will be conducted in normonatremic children admitted with acute appendicitis. On admission, all patients will receive an intravenous infusion of 50 mL/kg of Ringer’s acetate solution (131 mmol/L sodium, 4 mmol/L potassium, 2 mmol/L magnesium, 110 mmol/L chloride, 30 mmol/L acetate; Fresenius Kabi®) over four hours. This infusion will be followed by a maintenance fluid and electrolyte therapy phase consisting of a hypotonic 0.46% normal sodium chloride (80 mmol/L sodium, 20 mmol/L potassium, 100 mmol/L chloride; extempore solution) in 5% glucose solution until the start of the surgery. At the maintenance stage, infusion rate will be decreased to 80% of normal maintenance fluid therapy. The duration of the maintenance fluid phase will be approximately 12 hours. All participants will normally receive this treatment regardless of their involvement in this observational study. During surgery, fluids will be administered at anesthetist’s discretion. The total duartion of the observation for participants in this sudy will be until the end of surgery.
Intervention code [1] 317011 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323088 0
The primary outcome of this study is to evaluate mean plasma-sodium assessed by indirect ion-selective electrode method. This will be assessed by means of analyzing plasma-sodium
Timepoint [1] 323088 0
Timepoint: directly after surgery.
Secondary outcome [1] 387341 0
The occurrence of hyponatremia (plasma-sodium <135 mmol/L). This will be assessed by means of determining plasma-sodium will be assessed by indirect ion-selective electrode method.
Timepoint [1] 387341 0
Timepoint: directly after surgery

Eligibility
Key inclusion criteria
1). Admitted for suspected appendicitis.
2). Informed consent obtained from parents and if applicable from the child.
Minimum age
10 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1). Having received intravenous fluid therapy before the admission at our hospital
2). Plasma-sodium <135 mmol/L.
3). Documented diagnosis of renal, endocrine, or metabolic disease.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Statistical analyses will be performed using IBM SPSS Statistics for Windows version 24 (IBM Corp, Armonk, NY). All continuous variables will be presented as medians and interquartile ranges (IQR), unless otherwise stated. Paired t-test will be carried out to compare individual differences between admission and at the end of surgery, Pearson correlation coefficient will be used to measure association between two variables, Fisher’s exact test will be used to compare dichotomous variables, and analysis of variance (ANOVA) followed by the post-hoc Bonferroni test, will be performed for multiple pair-wise comparisons, i.e., between admission, before induction and at the end of surgery. Two-tailed p values less than 0.05 will be considered statistically significant.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
With the onset of the pandemic, there was a reorganization of hospital and medical spaces and staff to prioritize COVID-19–infected patients. This had a negative impact on the enrollment of patients in the study. In addition, since the primary endpoint was to evaluate the mean changes in PNa from hospital admission to the end of surgery, we calculate the sample size based on our previously published data, which also included patients that became hyponatremic. According to our calculation, a sample size of about 25 participants was needed to detect clinically relevant changes in PNa. However, none of the enrolled participants who underwent surgery (n = 21) developed post-operative hyponatremia. In view of all these facts, the study was stopped earlier than planned.
Date of first participant enrolment
Anticipated
1/06/2021
Actual
19/05/2021
Date of last participant enrolment
Anticipated
1/12/2021
Actual
28/02/2022
Date of last data collection
Anticipated
31/01/2022
Actual
4/03/2022
Sample size
Target
25
Accrual to date
Final
21
Recruitment outside Australia
Country [1] 22407 0
Sweden
State/province [1] 22407 0
Stockholm

Funding & Sponsors
Funding source category [1] 305126 0
Hospital
Name [1] 305126 0
Södersjukhuset AB, Stockholm.
Country [1] 305126 0
Sweden
Primary sponsor type
Individual
Name
Rafael Tomas Krmar
Address
Department of Physiology and Pharmacology (FyFa), Biomedicum, Solnavägen 9, SE-171 65 Solna, Sweden.

Country
Sweden
Secondary sponsor category [1] 305487 0
None
Name [1] 305487 0
Address [1] 305487 0
Country [1] 305487 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305497 0
Swedish Ethical Review Authority
Ethics committee address [1] 305497 0
Box 2110
S-750 02 Uppsala
Sweden
Ethics committee country [1] 305497 0
Sweden
Date submitted for ethics approval [1] 305497 0
01/07/2020
Approval date [1] 305497 0
05/10/2020
Ethics approval number [1] 305497 0
2020-03166

Summary
Brief summary
There is a prevalent view that in hospitalized patients with high circulating plasma vasopressin levels the administration of hypotonic fluid therapy is invariably associated with the occurrence of hyponatremia. Consequently, the prescription of hypotonic fluid therapy to hospitalized patients is discouraged.
In a previous study, conducted in children admitted with acute appendicitis, we have observed that correction of hypovolemia with near-isotonic fluid solution followed by hypotonic maintenance intravenous fluid therapy was not consistently associated with post-operative hyponatremia, and that the degree of hyponatremia in patients that became hyponatremic was always mild (Lindestam U. et al. Ped. Res. 2019). We noted that in patients with high circulating vasopressin levels, the degree of post-operative water retention declined significantly, as patients became euvolemic. This apparent escape from the antidiuretic effects of vasopressin attracted our attention and therefore is the focus of the proposed investigation.
Our assumption is that on admission most participants will have high circulating vasopressin levels. As a result of fluid therapy, we expect therefore a decrease of plasma-sodium at the end of surgery. The collection of new data has been planned based on an existing hypothesis, namely that we anticipate that some participants will show an escape from the antidiuretic effects of vasopressin. To shed light on this phenomenon, we will evaluate the changes in plasma-sodium from hospital admission to the end of surgery in acutely ill normonatremic children with appendicitis and relate them to key hormones involved in sodium and water homeostasis, to how much free water is being excreted or reabsorbed, and to surrogate markers of vasopressin-dependent trafficking of aquaporin-2 water channel.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100566 0
Dr Rafael Tomas Krmar
Address 100566 0
Karolinska Institutet, Department of Physiology and Pharmacology (FyFa), Biomedicum
Solnavägen 9, SE-171 65 Solna
Sweden
Country 100566 0
Sweden
Phone 100566 0
+46 733200146
Fax 100566 0
Email 100566 0
[email protected]
Contact person for public queries
Name 100567 0
Dr Rafael Tomas Krmar
Address 100567 0
Karolinska Institutet, Department of Physiology and Pharmacology (FyFa), Biomedicum
Solnavägen 9, SE-171 65 Solna
Sweden
Country 100567 0
Sweden
Phone 100567 0
+46 733200246
Fax 100567 0
Email 100567 0
[email protected]
Contact person for scientific queries
Name 100568 0
Dr Rafael Tomas Krmar
Address 100568 0
Karolinska Institutet, Department of Physiology and Pharmacology (FyFa), Biomedicum
Solnavägen 9, SE-171 65 Solna
Sweden
Country 100568 0
Sweden
Phone 100568 0
+46 733200146
Fax 100568 0
Email 100568 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All the individual participant data collected during the study.
When will data be available (start and end dates)?
Immediately following publication, no end date determined.
Available to whom?
Case-by-case basis at the discretion of primary sponsor.
Available for what types of analyses?
Only to achieve the aims of the approved proposal.
How or where can data be obtained?
Access subject to approvals by principal investigator; Rafael Tomas Krmar, email: [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
7183Study protocol    379377-(Uploaded-26-09-2020-16-13-18)-Study-related document.docx



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePerioperative water and electrolyte balance and water homeostasis regulation in children with acute surgery.2023https://dx.doi.org/10.1038/s41390-023-02509-1
N.B. These documents automatically identified may not have been verified by the study sponsor.