Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001311842
Ethics application status
Approved
Date submitted
14/08/2021
Date registered
27/09/2021
Date last updated
28/02/2024
Date data sharing statement initially provided
27/09/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
REstrictive vs StandarD FlUid Management in Mechanically Ventilated ChildrEn Admitted to Paediatric Intensive Care Unit (PICU) - a Pilot Randomised Controlled Trial
Scientific title
REstrictive vs StandarD FlUid Management in Mechanically Ventilated ChildrEn Admitted to PICU - a Pilot Randomised Controlled Trial (REDUCE-1)
Secondary ID [1] 305044 0
None
Universal Trial Number (UTN)
U1111-1268-6516
Trial acronym
REDUCE-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fluid overload in critically ill children 323230 0
Condition category
Condition code
Emergency medicine 320812 320812 0 0
Other emergency care
Public Health 321071 321071 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1:1 random assignment of individual patients into two groups – restrictive versus standard fluid strategy.
Stratified by primary diagnosis (cardiac/non-cardiac) prior to enrolment.
Restrictive fluid bundle (REDUCE bundle): Elements of the bundle will include restrictive maintenance fluid strategy, limiting fluid boluses, reducing volumes of drug delivery and initiating diuretics or peritoneal dialysis earlier.
Duration of exposure from randomisation to until discharge from the paediatric intensive care unit.

Both doctors and nurses will deliver the restrictive fluid bundle to patients according to the study guideline developed by the PI in consultation with the PICU pharmacist and dietician. The guideline for the restrictive fluid bundle is inline with current unit practice of caring for fluid restricted patients. Assessment of adherence to the bundle will be captured using data obtained from the PICU electronic clinical record system.

Using a restrictive bundle will include reducing:
1. Maintenance fluids to 50% (standards care is 75% for non-cardiac patients, 50% for patients undergoing cardiopulmonary bypass)
2. Smaller fluid bolus 5ml/kg (standard care:10-20ml/kg)
3. Drug dilutions will be assessed daily to see if they can be safely reduced. Limiting 0.9% saline flushes and post medication flushes to 3mls (standard care up to 10ml) or if line requires fluid to keep vein open (TKVO) limiting to 0.5ml/hr (standard care 1ml/hr)
4. Strengthen TPN concentration if possible
4. If fluid removal is required, consider commencing diuretics within 24hours of randomisation (standard care commencement usually day 1 or 2)
5. Peritoneal dialysis. Consider commencing within 24 hours of randomisation if clinically indicated (Standard care: usually commenced on day 1 or 2 however clinician may start when they feel it is appropriate)
Intervention code [1] 321439 0
Treatment: Other
Comparator / control treatment
Standard care of patients on the paediatric intensive care unit as per institutional policies.
Control group
Active

Outcomes
Primary outcome [1] 328618 0
Fluid balance obtained from the electronic medical record ( Metavision) which is completed hourly by bedside nurse
Timepoint [1] 328618 0
At 48 hours after randomisation
Secondary outcome [1] 399645 0
Negative fluid balance >10% body weight in one calendar day. The bedside nurse will input fluid input and output on an hourly basis into the clinical information system (Metavision). The cumulative total for the previous 24 hours on PICU will be calculated within the clinical information system.
Timepoint [1] 399645 0
Each morning from the day of randomisation until 48 hours after randomisation
Secondary outcome [2] 399646 0
New onset Acute Kidney Injury (AKI) which will be assessed using results from daily blood tests taken by the bedside nurse. The results will be sourced from Metavision.
Defined as per KDIGO criteria.
Timepoint [2] 399646 0
From randomisation to until PICU discharge - censored at 7 days
Secondary outcome [3] 399647 0
Incidence of clinically relevant central venous thrombosis. The Bedside nurse will monitor for signs and symptoms such as swelling, pain and redness of the area and dysfunction of the catheter. This will be documented and sourced from Metavision (clinical information system).
Timepoint [3] 399647 0
From randomisation to until PICU discharge - censored at 7 days
Secondary outcome [4] 399648 0
Incidence of secondary lactate rise greater than or equal to 3mmol/L from baseline value at randomisation in the 24 hours after randomisation. Assessed from daily biochemistry results and routine blood gas measurements. The results will be sourced from Metavision.
Timepoint [4] 399648 0
Until 48 hours after randomisation
Secondary outcome [5] 399649 0
Incidence of urine output <0.5mls/kg/hr for 4 consecutive hours in the 24 hours after randomisation. Assessed using data from fluid balance record documented in Metavision.
Timepoint [5] 399649 0
Until 48 hours after randomisation
Secondary outcome [6] 399650 0
Number of patients recruited. Eligible and Randomised patient will be recorded using REDCap, a purpose built database hosted by the University of Queensland by the research nurse.
Timepoint [6] 399650 0
To the end of the trial recruitment
Secondary outcome [7] 399651 0
Proportion of recruited to eligible patients. Eligible and Randomised patient will be recorded using REDCap, a purpose built database hosted by the University of Queensland by the research nurse.
Timepoint [7] 399651 0
Until the completion of trial recruitment
Secondary outcome [8] 399652 0
Overall percentage adherence to each of the bundle elements in patients randomised to restrictive arm. This information will be obtained from data collected on Metavision.
Timepoint [8] 399652 0
Adherence in each recruit assessed until discharge from PICU.
Secondary outcome [9] 399653 0
PICU free survival. This information will be obtained from data collected on Metavision and data reported to the Australia New Zealand Paediatric Intensive Care Registry.
Timepoint [9] 399653 0
Censored at 28 days post randomisation
Secondary outcome [10] 399654 0
Ventilator free days. This information will be obtained from data collected on Metavision.
Timepoint [10] 399654 0
Censored at 28 days post randomisation
Secondary outcome [11] 399655 0
PICU length of stay. This information will be obtained from data collected on Metavision.
Timepoint [11] 399655 0
Until discharge from PICU
Secondary outcome [12] 399656 0
Hospital length of stay. This information will be obtained from data collected on Metavision.
Timepoint [12] 399656 0
Until discharge from hospital
Secondary outcome [13] 399657 0
Mortality. This information will be obtained from data collected on Metavision and data reported to the Australia New Zealand Paediatric Intensive Care Registry.
Timepoint [13] 399657 0
Censored at 28 days post randomisation.
Secondary outcome [14] 399658 0
Duration of inotropic support. This information will be obtained from data recorded on Metavision.
Timepoint [14] 399658 0
In every 24 hours after randomisation upto 7 days or dicharge from PICU
Secondary outcome [15] 399659 0
Vasoactive Inotrope Score greater than or equal to 20. This information will be obtained from data recorded on Metavision.
Timepoint [15] 399659 0
In the 48 hours after randomisation.
Secondary outcome [16] 400637 0
Number of patients randomised at each of the time points. This information will be obtained from data collected on Metavision.
Timepoint [16] 400637 0
Up to 48 hours post randomisation at three timepoints - day 0, day 1 and day 2.

Eligibility
Key inclusion criteria
1. Admitted to PICU (and)
2. Mechanically ventilated at the time of randomisation (and)
3. Expected to be ventilated (if randomised at admission) or already ventilated (for those randomised on day 1 or 2) for greater than or equal to 6 hours
4. Age greater than or equal to 0 days to less than 18 years (17 years and 364 days)
Minimum age
0 Days
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Admitted to PICU for greater than or equal to 48 hours
2. Children re-admitted to PICU less than or equal to 6 months of index (first randomisation) admission
3. Children needing hyperhydration for the risk of tumor lysis syndrome
4. Diabetic ketoacidosis
5. Post organ transplant patients
6. Patients in whom end of life care or palliative care has been instituted

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Concealed by using central randomisation by using online REDCap database.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computerised sequence generation - Electronic variable block randomisation schedule with block sizes of 4 and 6 and 1:1 allocation, stratified by primary diagnosis (cardiac/non-cardiac) prior to enrolment, into restrictive-fluid and standard care arms will be constructed and imported into the study REDCap database.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
To keep the trial pragmatic, we have chosen a non-blinded study strategy. It is not possible to blind the clinician as the elements of the bundle are interventions that are employed as part of standard care.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be used to report on the baseline characteristics of the total study cohort, each intervention group and the pre-defined subgroups. All endpoints will be evaluated using the appropriate descriptive statistics. The estimate of the effect size (along with the 95% confidence interval) will be calculated and presented, however no p-values will be reported. Participants will be evaluated in the groups to which they were randomised, regardless of treatment received (i.e. intention-to-treat). Regardless of crossover, we will perform a per-protocol analysis.
A priori sub-group analyses:
• Age – Neonates, greater than 1 month to less than 1year and greater than or equal to 1 year
• Elective / Non-elective
• Cardiac / Non-cardiac
• High and low patient acuity stratified according to admission Paediatric Index of Mortality 3 (PIM3) scores. High acuity defined as PIM3 greater than or equal to 0.05 and low acuity less than 0.05.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
1/10/2021
Actual
24/11/2021
Date of last participant enrolment
Anticipated
24/11/2023
Actual
20/11/2023
Date of last data collection
Anticipated
15/04/2024
Actual
Sample size
Target
154
Accrual to date
Final
154
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 20243 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [2] 23045 0
Sydney Children's Hospital - Randwick
Recruitment postcode(s) [1] 34981 0
4101 - South Brisbane
Recruitment postcode(s) [2] 38373 0
2031 - Randwick
Recruitment outside Australia
Country [1] 24042 0
Switzerland
State/province [1] 24042 0
Zurich

Funding & Sponsors
Funding source category [1] 309441 0
Charities/Societies/Foundations
Name [1] 309441 0
Children's Hospital Foundation
Country [1] 309441 0
Australia
Primary sponsor type
University
Name
The University of Queensland
Address
The University of Queensland, 62 Graham St, South Brisbane, Queensland 4101.
Country
Australia
Secondary sponsor category [1] 310408 0
None
Name [1] 310408 0
Address [1] 310408 0
Country [1] 310408 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309233 0
Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee
Ethics committee address [1] 309233 0
Ethics committee country [1] 309233 0
Australia
Date submitted for ethics approval [1] 309233 0
12/08/2021
Approval date [1] 309233 0
01/09/2021
Ethics approval number [1] 309233 0
HREC/21/QCHQ/77514

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

Contacts
Principal investigator
Name 113438 0
Dr Sainath Raman
Address 113438 0
Paediatric Intensive Care Unit, Queensland Children's Hospital AND
Paediatric Critical Care Research Group, Child Health Research Centre, The University of Queensland, 62 Graham St, South Brisbane, Queensland, 4101.
Country 113438 0
Australia
Phone 113438 0
+61 432956149
Fax 113438 0
Email 113438 0
[email protected]
Contact person for public queries
Name 113439 0
Sainath Raman
Address 113439 0
Paediatric Intensive Care Unit, Queensland Children's Hospital AND
Paediatric Critical Care Research Group, Child Health Research Centre, The University of Queensland, 62 Graham St, South Brisbane, Queensland, 4101.
Country 113439 0
Australia
Phone 113439 0
+61 432956149
Fax 113439 0
Email 113439 0
[email protected]
Contact person for scientific queries
Name 113440 0
Sainath Raman
Address 113440 0
Paediatric Intensive Care Unit, Queensland Children's Hospital AND
Paediatric Critical Care Research Group, Child Health Research Centre, The University of Queensland, 62 Graham St, South Brisbane, Queensland, 4101.
Country 113440 0
Australia
Phone 113440 0
+61 432956149
Fax 113440 0
Email 113440 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?
Anonymised data could be shared on a case-by-case basis after appropriate approvals are attained. De-identified individual participant data of published results only will be shared.
When will data be available (start and end dates)?
Start date: 01/09/2023
End date: 01/09/2024
Available to whom?
Anonymised data could be shared on a case-by-case basis after appropriate approvals are attained.
Available for what types of analyses?
Exploratory secondary analyses
How or where can data be obtained?
Anonymised data could be shared by the PI on a case-by-case basis after appropriate approvals are attained. Contact email - [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
12873Study protocol  [email protected]
13106Ethical approval  [email protected]



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.