Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609000924257
Ethics application status
Approved
Date submitted
14/10/2009
Date registered
27/10/2009
Date last updated
6/02/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised controlled trial of Plasmalyte148 with 5% dextrose compared to 0.45% sodium chloride with 5% dextrose for maintenance intravenous fluid therapy in hospitalised children.
Scientific title
In hospitalised children requiring maintenance intravenous therapy, does Plasmalyte148 with 5% dextrose compared to 0.45% sodium chloride with 5% dextrose result in less hyponatraemia?
Secondary ID [1] 251998 0
Royal Children's Hospital HREC 29071
Secondary ID [2] 252022 0
Royal Children's Hospital HREC 29071
Universal Trial Number (UTN)
Trial acronym
PIMS (Paediatric Intravenous Maintenance Solution)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prevention of iatrogenic hyponatraemia 252004 0
Condition category
Condition code
Other 252198 252198 0 0
Conditions of unknown or disputed aetiology (such as chronic fatigue syndrome/myalgic encephalomyelitis)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Plasmalyte148 with 5% dextrose
Mode of administration: intravenous infusion
Rate of infusion: to be determined by the treating clinician, but must be between 50 - 150% of standard maintenance rates (based on the 100/50/20 or 4/2/1 rule).
Duration of infusion: Subjects will remain in the trial while they are receiving intravenous fluids at a rate of at least 50% maintenance, or for 72 hours (whichever is sooner).
Intervention code [1] 241413 0
Treatment: Drugs
Comparator / control treatment
0.45% sodium chloride with 5% dextrose Mode of administration: intravenous infusion Rate of infusion: to be determined by the treating clinician, but must be between 50 - 150% of standard maintenance rates (based on the 100/50/20 rule as described by Holliday and Segar). Duration of infusion: Subjects will remain in the trial while they are receiving intravenous fluids at a rate of at least 50% maintenance, or for 72 hours (whichever is sooner).
Control group
Active

Outcomes
Primary outcome [1] 253075 0
The primary outcome is the proportion of subjects in each treatment group that develop hyponatraemia [serum sodium measurement that is below the normal range minimum (135mmol/L) and has decreased by at least 3mmol/L compared with the baseline measurement] at any time point during the treatment period.
Timepoint [1] 253075 0
Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner). They will have blood tests performed at 0, 6, 24, 48 and 72 hours, while they remain in the trial. Additional blood tests may be performed between these time points, as determined by the treating clinician. There is no maximum number of blood tests which may be performed. All blood tests performed may be used in the analysis.
Secondary outcome [1] 257918 0
The proportion of subjects in each treatment group with a measurement of hypernatraemia (serum sodium >145 with an increase of at least 3mmol/L compared with the baseline measurement) at any time during the study period.
Timepoint [1] 257918 0
Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner). They will have blood tests performed at 0, 6, 24, 48 and 72 hours, while they remain in the trial. Additional blood tests may be performed between these time points, as determined by the treating clinician. There is no maximum number of blood tests which may be performed. All blood tests performed may be used in the analysis.
Secondary outcome [2] 257919 0
The proportion of subjects in each treatment group with a measurement of severe hyponatraemia (serum sodium <130 with a decrease of at least 3mmol/L compared with the baseline measurement) at any time during the study period.
Timepoint [2] 257919 0
Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner). They will have blood tests performed at 0, 6, 24, 48 and 72 hours, while they remain in the trial. Additional blood tests may be performed between these time points, as determined by the treating clinician. There is no maximum number of blood tests which may be performed. All blood tests performed may be used in the analysis.
Secondary outcome [3] 257920 0
The proportion of subjects in each treatment group with a measurement of severe hypernatraemia (serum sodium >150 with an increase of at least 3mmol/L compared with the baseline measurement) at any time during the study period.
Timepoint [3] 257920 0
Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner). They will have blood tests performed at 0, 6, 24, 48 and 72 hours, while they remain in the trial. Additional blood tests may be performed between these time points, as determined by the treating clinician. There is no maximum number of blood tests which may be performed. All blood tests performed may be used in the analysis.
Secondary outcome [4] 257922 0
A comparison of fluid status in each treatment group. This will be clinically assessed by the treating clinician who will state whether the subject is clinically dehydrated, euvolaemia or overhydrated. They will also record which clinical features or investigations resulted in this assessment.
Timepoint [4] 257922 0
Clinical assessments will occur at 0, 6, 24, 48 and 72 hours as well as at the end of treatment.
Secondary outcome [5] 264739 0
Mean serum sodium at each time point
Timepoint [5] 264739 0
The mean serum sodium at 6, 24, 48 and 72 hours will be examined, while the subject remains in the trial.
Secondary outcome [6] 264740 0
Change in weight from baseline using standard calibrated digital scales.
Timepoint [6] 264740 0
Change in weight at 6, 24, 48 and 72 hours will be examined, while the subject remains in the trial.
Secondary outcome [7] 264741 0
Number of intravenous (IV) cannula reinsertions required.
Timepoint [7] 264741 0
Number of reinsertions required for each subject throughout the study period.
Secondary outcome [8] 264742 0
Proportion of electrolyte imbalances in each study group including hyperchloraemia, high serum bicarbonate and high serum magnesium.
Timepoint [8] 264742 0
Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner). They will have blood tests performed at 0, 6, 24, 48 and 72 hours, while they remain in the trial. Additional blood tests may be performed between these time points, as determined by the treating clinician. There is no maximum number of blood tests which may be performed. All blood tests performed may be used in the analysis.
Secondary outcome [9] 264743 0
Mean urinary sodium
Timepoint [9] 264743 0
24 hours after starting treatment
Secondary outcome [10] 301040 0
Proportion of patients with seizures in each study group.
Timepoint [10] 301040 0
During the study period: Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner).
Secondary outcome [11] 301041 0
Cerebral oedema, confirmed by neuroimaging (CT or MRI).
Timepoint [11] 301041 0
During the study period: Subjects will remain in the trial while they are receiving at least 50% of standard maintenance fluid rates, or for 72 hours (whichever is sooner).

Eligibility
Key inclusion criteria
To be eligible for this study, each subject must be aged between 3 months and 18 years old, be a patient at the Royal Children's Hospital in Melbourne and be assessed by an independent clinician as requiring intravenous fluid therapy at a rate of at least 50% and up to 150% recommended maintenance.
Minimum age
3 Months
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
An initial plasma sodium level of <130 or >150. A known abnormality of antidiuretic hormone secretion. Diabetic ketoacidosis. Renal disease requiring dialysis. A known disorder causing excessive renal sodium excretion. Pre or postoperative neurosurgical or craniofacial patients, requiring opening of the cranial cavity. Oncology patients requiring protocol-determined chemotherapy hydration. Children with inborn errors of metabolism requiring protocol determined fluid therapy. Proven meningitis. Severe liver disease. Conditions where intravenous fluids are anticipated to be given for less than six hours.

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)
Initially sealed opaque envelopes. It is anticipated that an on-line enrollment program will be available within two months of the study commencing - at this point this computerised system will be used for treatment allocation.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation sequence will be developed by a statistician using block randomisation.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
21/12/2009
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
690
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 243877 0
Charities/Societies/Foundations
Name [1] 243877 0
Murdoch Children's Research Institute
Country [1] 243877 0
Australia
Funding source category [2] 243878 0
Hospital
Name [2] 243878 0
Department of Anaesthesia, Royal Children's Hospital
Country [2] 243878 0
Australia
Primary sponsor type
Hospital
Name
Royal Children's Hospital
Address
Flemington Rd,
Parkville, Victoria, 3052
Country
Australia
Secondary sponsor category [1] 251225 0
None
Name [1] 251225 0
Address [1] 251225 0
Country [1] 251225 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 243997 0
Human Research Ethics Committee, Royal Children's Hospital
Ethics committee address [1] 243997 0
Flemington Rd,
Parkville, Victoria, 3052
Ethics committee country [1] 243997 0
Australia
Date submitted for ethics approval [1] 243997 0
Approval date [1] 243997 0
04/10/2009
Ethics approval number [1] 243997 0
29071

Summary
Brief summary
When children are hospitalised, they often require fluid through an intravenous line (or “drip”). This is usually because they can’t eat or drink enough to stay hydrated. The fluid is made up of water, sugar and some salts.

There is uncertainty regarding the ideal sodium concentration for fluid given through a drip. Sodium is a salt which is naturally contained in the body. However, when sodium levels in the body rise or fall suddenly, it is dangerous. In rare cases, this has led to brain damage and death.

Currently, when children need intravenous fluid, they are usually given a fluid that contains about half the concentration of sodium that the blood in the body naturally contains. This fluid is called 0.45% sodium chloride. For most children, this doesn’t have a bad effect. However, in some sick children, this fluid “dilutes” the blood, causing the blood sodium level to drop quickly. This side effect is rare, but is potentially very serious.

We believe that we can make the fluid safer by increasing the sodium concentration. This should make it less likely that the sodium level in the blood will drop suddenly. This, in turn, should reduce the number of children who have bad side effects.

We will conduct a study that compares the fluid we currently use (0.45% sodium chloride) with a fluid that contains more sodium (Plasmalyte148). Plasmalyte148 contains approximately the same concentration of sodium as is naturally contained in the blood. This is approximately double the concentration of sodium when compared with 0.45% sodium chloride.

Children at the Royal Children’s Hospital who require fluid through a drip will be asked to participate in the trial. They will be randomly allocated either to 0.45% sodium chloride or to Plasmalyte148. The participants will not know the type of fluid they receive, nor will their doctors. The participants will be monitored with regular blood tests.

The children will stay in the study for three days, or until they no longer require most of their hydration through a drip. We will compare blood test results for the children in each group (the 0.45% sodium chloride group compared with the Plasmalyte148 group). We will determine whether Plasmalyte148 results in more normal blood sodium results when compared with the fluid we currently use.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30389 0
Dr Dr Sarah McNab
Address 30389 0
c/o Department of General Medicine
Royal Children's Hospital
Flemington Rd
Parkville, Victoria
Australia
3052
Country 30389 0
Australia
Phone 30389 0
+61 3 9345 4154
Fax 30389 0
Email 30389 0
sarah.mcnab@rch.org.au
Contact person for public queries
Name 13636 0
Dr Dr Sarah McNab
Address 13636 0
c/o Centre for International Child Health
Royal Children's Hospital
Flemington Rd
Parkville, Victoria, 3052
Country 13636 0
Australia
Phone 13636 0
+61 3 9345 4154
Fax 13636 0
Email 13636 0
sarah.mcnab@rch.org.au
Contact person for scientific queries
Name 4564 0
Dr Dr Sarah McNab
Address 4564 0
c/o Centre for International Child Health
Royal Children's Hospital
Flemington Rd
Parkville, Victoria, 3052
Country 4564 0
Australia
Phone 4564 0
+61 3 9345 4154
Fax 4564 0
Email 4564 0
sarah.mcnab@rch.org.au

No information has been provided regarding IPD availability


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.