ANZCTR - Registration

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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

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]

Nil known

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Appendicitis

Dehydration

Condition category

Condition code

Surgery

Other surgery

Oral and Gastrointestinal

Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Metabolic and Endocrine

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]

Not applicable

Comparator / control treatment

No control group

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

Timepoint: directly after surgery.

Secondary outcome [1]

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]

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?

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

Accrual to date

Final

Recruitment outside Australia

Country [1]

Sweden

State/province [1]

Stockholm

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Södersjukhuset AB, Stockholm.

Address [1]

Sjukhusbacken 10, 118 83 Stockholm.

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Swedish Ethical Review Authority

Ethics committee address [1]

Box 2110
S-750 02 Uppsala
Sweden

Ethics committee country [1]

Sweden

Date submitted for ethics approval [1]

01/07/2020

Approval date [1]

05/10/2020

Ethics approval number [1]

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

Dr Rafael Tomas Krmar

Address

Karolinska Institutet, Department of Physiology and Pharmacology (FyFa), Biomedicum
Solnavägen 9, SE-171 65 Solna
Sweden

Country

Sweden

Phone

+46 733200146

Fax

rafael.krmar@ki.se

Contact person for public queries

Name

Rafael Tomas Krmar

Address

Karolinska Institutet, Department of Physiology and Pharmacology (FyFa), Biomedicum
Solnavägen 9, SE-171 65 Solna
Sweden

Country

Sweden

Phone

+46 733200246

Fax

rafael.krmar@ki.se

Contact person for scientific queries

Name

Rafael Tomas Krmar

Address

Karolinska Institutet, Department of Physiology and Pharmacology (FyFa), Biomedicum
Solnavägen 9, SE-171 65 Solna
Sweden

Country

Sweden

Phone

+46 733200146

Fax

rafael.krmar@ki.se

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: rafael.krmar@ki.se

What supporting documents are/will be available?

Doc. No.	Type	Citation	Link	Email	Other Details	Attachment
7183	Study 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

Source	Title	Year of Publication	DOI
Embase	Perioperative water and electrolyte balance and water homeostasis regulation in children with acute surgery.	2023	https://dx.doi.org/10.1038/s41390-023-02509-1

N.B. These documents automatically identified may not have been verified by the study sponsor.

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