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Trial registered on ANZCTR


Registration number
ACTRN12617001614381
Ethics application status
Approved
Date submitted
23/11/2017
Date registered
8/12/2017
Date last updated
30/08/2022
Date data sharing statement initially provided
19/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Early peritoneal dialysis in infants after heart operation
Scientific title
Early prophylactic peritoneal dialysis in infants post cardiac surgery: a randomised, open, two group trial
Secondary ID [1] 293429 0
None
Universal Trial Number (UTN)
Trial acronym
EPICS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac surgery for congenital heart disease 305593 0
Condition category
Condition code
Cardiovascular 304815 304815 0 0
Diseases of the vasculature and circulation including the lymphatic system
Surgery 305013 305013 0 0
Other surgery

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Infants in the treatment group will be commenced on peritoneal dialysis as soon as possible (no later than 60 minutes) after admission to ICU following cardiac surgery. The treatment will be provided for a total of 24 hours (24 cycles in total)
Intervention code [1] 299670 0
Treatment: Other
Intervention code [2] 299729 0
Prevention
Comparator / control treatment
Infants in the control arm will NOT receive peritoneal dialysis for the first 24 hour period following cardiac surgery. However, peritoneal dialysis may be commenced in the first 24 hours in the control group if there is: (1) serum potassium 6.5 mmol/L; (2) or severe metabolic acidosis (pH < 7.25 with a Co2 < 40); or (3) urine output <0.5 ml/kg/hr for 6 hrs or more despite frusemide infusion.

Update: The PD catheter will be left clamped during the first 24 hour period following cardiac surgery in the control arm
Control group
Active

Outcomes
Primary outcome [1] 304028 0
Composite outcome (one or more of death from any cause, cardiac arrest, emergency chest reopening and requirement for extracorporeal membrane oxygenation).

This outcome measure is collected by review of electronic medical records
Timepoint [1] 304028 0
Within 90 days after randomisation
Secondary outcome [1] 340741 0
Vasoactive-inotrope score (VIS)

VIS = Dopamine (mcg/kg/min) + dobutamine (mcg/kg/min) + 100 x adrenaline (mcg/kg/min) + 10 x milrinone (mcg/kg/min) + 10,000 x vasopressin (U/kg/min) + 100 x noradrenaline (mcg/kg/min)
Timepoint [1] 340741 0
At 24 hours post ICU admission
Secondary outcome [2] 340742 0
Cumulative percent fluid balance.

This outcome is assessed by fluid balance which is routinely collected on the bedside based on total intake and output.
Cumulative percent fluid balance = (total fluid balance since admission [Litre]) / (weight [kg]) ×100
Timepoint [2] 340742 0
By end of day 2 of surgery (Midnight of the 2nd postoperative night)
Secondary outcome [3] 340743 0
ICU length of stay.

This outcome is assessed by review of electronic medical records
Timepoint [3] 340743 0
Following cardiac surgery

(Maximum follow-up :1 year)
Secondary outcome [4] 340744 0
Hospital length of stay

This outcome is assessed by review of electronic medical records
Timepoint [4] 340744 0
Following cardiac surgery

(Maximum follow-up :1 year)
Secondary outcome [5] 340745 0
Duration of mechanical ventilation

This outcome is assessed by review of electronic medical records
Timepoint [5] 340745 0
Following cardiac surgery

(Maximum follow-up :1 year)
Secondary outcome [6] 340746 0
Serum interlukin-6
Timepoint [6] 340746 0
At 0, 6 and 24 hours from admission to ICU following cardiac surgery
Secondary outcome [7] 340919 0
Serum interlukin-8
Timepoint [7] 340919 0
At 0, 6 and 24 hours from admission to ICU following cardiac surgery
Secondary outcome [8] 340920 0
Serum interlukin-10
Timepoint [8] 340920 0
At 0, 6 and 24 hours from admission to ICU following cardiac surgery
Secondary outcome [9] 340921 0
Serum Tumour necrosis factor - alpha
Timepoint [9] 340921 0
At 0, 6 and 24 hours from admission to ICU following cardiac surgery
Secondary outcome [10] 340923 0
Mortality
Timepoint [10] 340923 0
At 90 days from randomisation
Secondary outcome [11] 340925 0
Requirement for ECMO
Timepoint [11] 340925 0
At 90 days from randomisation
Secondary outcome [12] 340926 0
Cardiac arrest
Timepoint [12] 340926 0
At 90 days from randomisation
Secondary outcome [13] 340927 0
Emergency chest reopening
Timepoint [13] 340927 0
At 90 days from randomisation
Secondary outcome [14] 340928 0
Total volume of packed red blood cell transfusion
Timepoint [14] 340928 0
At 90 days from randomisation
Secondary outcome [15] 340929 0
Incidence of post-operative infection
Timepoint [15] 340929 0
At 90 days from randomisation
Secondary outcome [16] 340930 0
Number of days receiving vasoactive medications
Timepoint [16] 340930 0
At 90 days from randomisation
Secondary outcome [17] 340931 0
Rate of readmission to ICU
Timepoint [17] 340931 0
At 90 days from randomisation
Secondary outcome [18] 340932 0
Renal failure requiring renal replacement therapy
Timepoint [18] 340932 0
At 90 days from randomisation
Secondary outcome [19] 340933 0
Incidence of brain injury (new seizures or neuroimaging findings)
Timepoint [19] 340933 0
At 90 days form randomisation
Secondary outcome [20] 340934 0
Overall hospital costs
**This will be calculated based on previously described methods (Doyle 1989:: MJA vol150 page558-568). Cost in dollars will recalculated based on the assumption that the proportion of nursing staff within hospital who were assigned to intensive care unit and cardiology ward represented the same proportion of the hospital's operating costs that were expended in the care of infants in these wards.
Timepoint [20] 340934 0
12 months following randomisation

Eligibility
Key inclusion criteria
Infants less than or equal to 180 days of age who have had cardiac surgery (in RACHS-1 categories 3 to 6) with cardiopulmonary bypass will be eligible, providing they have a peritoneal dialysis catheter in place at the time of admission to ICU and are expected to be ventilated for at least 24 hours
Minimum age
0 Days
Maximum age
180 Days
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The exclusions will be: 1) if withdrawal of treatment is being considered 2) infants who have already participated in the same trial during a previous cardiac surgery 3) children already on extracorporeal membrane oxygenation (ECMO) at the time of admission from the operating theatre and 4) infants whose parents refuse consent.

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)
Allocation concealment is achieved by an independent centralised computer allocation process. Allocation is only revealed once eligibility is confirmed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation is computer generated, will be in blocks and stratified by RACHS-1 category (3- 4, 5-6)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The study is a randomised, open, two group trial. Eligible participants are randomised to either Early peritoneal dialysis (Treatment group) OR No early peritoneal dialysis (Control group)
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Sample Size Estimation
Based on an expected composite primary outcome rate of 20% in the control group and 5% in the intervention group, we calculated we will need a total of 39 primary endpoints using an alpha error of < 0.01 and power of 90%. If the control group had a primary outcome rate of 20% throughout the trial, 156 infants will be needed in the control group and 156 in the intervention group (total 312). Data collected in the paediatric intensive care unit at the Royal Children’s hospital (2012-2015) was used to calculate primary endpoint rate in children after cardiac surgery and who had a peritoneal dialysis catheter:

Analysis plan
Analysis will be by intention-to-treat. For analysis of primary outcome, Cox regression adjusted for age at the time of randomisation and with censoring at the time of loss to follow-up will be used to calculate hazard ratio (HRs) with 95% CI. Alternatively a chi-squared test (or Fisher’s exact test) may be used for the primary outcome if loss to follow-up is minimal. Risk ratios and risk difference between the treatment groups will also be calculated (with 95% CI). Measures of the spread of the data will include 95% confidence interval, standard deviation, and interquartile range as appropriate. A per-protocol analysis will also be performed in which data from any patients in the intervention arm who did not receive peritoneal dialysis within 6 hrs of completion of CPB and data from any patients in the control arm who received peritoneal dialysis within 6 hours of completion of CPB will be excluded.
For secondary outcomes, tests for proportions (chi-squared test or Fisher’s exact test) will be used of categorical variables and unpaired test (if normality assumptions met) or rank-sum test will be s used for continuous variables. For cytokine measurements at 0, 6 and 24 hours, analysis of covariance controlling for baseline value and including study group in the model will be used will be used for analysis. The pre-specified groups for sub-group analyses are: RACHS-1 category (3-4, 5-6) and CPB duration ( 150 min vs. > 150 min). Appropriate interaction term will be used to test whether or not the sub-groups will be associated with different treatment outcome. All statistical tests will be two-sided with an alpha of 0.05, except for the primary outcome variable where a lower p value will be used to allow for appropriate alpha spending (depending on the number of planned interim analysis). Statistical analysis will be performed using Stata software (StataCorp, College Station, Texas).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
11/12/2017
Actual
27/09/2019
Date of last participant enrolment
Anticipated
11/12/2023
Actual
Date of last data collection
Anticipated
11/12/2024
Actual
Sample size
Target
312
Accrual to date
205
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9427 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 18137 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 298056 0
Charities/Societies/Foundations
Name [1] 298056 0
Murdoch Children's Research Institute
Country [1] 298056 0
Australia
Primary sponsor type
Hospital
Name
The Royal Children's Hospital Melbourne
Address
Royal Children's Hospital
50 Flemington Road, Parkville Victoria 3052 Australia
Country
Australia
Secondary sponsor category [1] 297130 0
None
Name [1] 297130 0
None
Address [1] 297130 0
None
Country [1] 297130 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299075 0
HREC, The Royal Children's Hospital Melbourne
Ethics committee address [1] 299075 0
Human Research and Ethics Committee
Royal Children's Hospital
50 Flemington Road, Parkville Victoria 3052 Australia
Ethics committee country [1] 299075 0
Australia
Date submitted for ethics approval [1] 299075 0
Approval date [1] 299075 0
22/11/2017
Ethics approval number [1] 299075 0
HREC reference number: HREC/17/RCHM/246

Summary
Brief summary
Background:
Children undergoing heart surgery require cardiopulmonary bypass. This is a technique which takes over the work of the heart and lungs so the surgeon can perform the operation. The use of cardiopulmonary bypass often causes a reaction in the child called systemic inflammatory response (or SIRS for short). Children who develop SIRS are much more likely to have complications in intensive care (cardiac arrest, need for time on a breathing machine, prolonged intensive care stay and even death). Doctors and nurses at the Royal Children’s Hospital are very interested in studying and preventing SIRS.

Peritoneal dialysis is a therapy often used in children after heart surgery; it is also used in children and adults to provide artificial kidney function. It involves placing fluid in the abdomen and using the lining to remove fluids and substances. We have observed that the early use of this therapy soon after heart operation is associated with improved outcomes. Peritoneal dialysis might reduce the risk of SIRS.


Proposed study:
We plan to study the role of early peritoneal dialysis in preventing the complications of SIRS in babies less than six months of age. The study will be conducted in the Cardiac Intensive Care Unit at the Royal Children’s Hospital, Melbourne.
We have calculated we will need 312 infants in the study and hope to find out if early peritoneal dialysis helps reduce complications of SIRS following cardiac surgery.
Babies will either get early peritoneal dialysis or normal care. Early peritoneal dialysis will start within an hour of arriving in the intensive care unit after heart surgery and will continue for 24 hours. Normal care babies will only get peritoneal dialysis if they need it for artificial kidney function.


Potential implications for child health:
This study will help to answer the question: “Does early peritoneal dialysis really help babies after heart surgery ?”.It will help make decisions about treatments after heart surgery. This is important for doctors and nurses working in intensive care units around the world. Peritoneal dialysis is a low cost treatment and if early commencement of this therapy after surgery is shown to positively influence outcomes it will have important implications for children born with congenital heart disease.
Trial website
None
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79210 0
Dr Siva Namachivayam
Address 79210 0
Dr Siva Namachivayam
Paediatric Intensive Care Physician
The Royal Children's Hospital Melbourne
50 Flemington Road | Parkville | 3052 | VIC
Country 79210 0
Australia
Phone 79210 0
+61 3 9345 5224
Fax 79210 0
Email 79210 0
siva.namachivayam@rch.org.au
Contact person for public queries
Name 79211 0
Dr Siva Namachivayam
Address 79211 0
The Royal Children's Hospital Melbourne
50 Flemington Road | Parkville | 3052 | VIC
Country 79211 0
Australia
Phone 79211 0
+61 3 9345 5224
Fax 79211 0
Email 79211 0
siva.namachivayam@rch.org.au
Contact person for scientific queries
Name 79212 0
Dr Siva Namachivayam
Address 79212 0
The Royal Children's Hospital Melbourne
50 Flemington Road | Parkville | 3052 | VIC
Country 79212 0
Australia
Phone 79212 0
+61 3 9345 5224
Fax 79212 0
Email 79212 0
siva.namachivayam@rch.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not decided yet


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
SourceTitleYear of PublicationDOI
Dimensions AIStudy protocol and statistical analysis plan for the Early Peritoneal Dialysis in Infants after Cardiac Surgery (EPICS) trial2022https://doi.org/10.51893/2022.2.oa9
N.B. These documents automatically identified may not have been verified by the study sponsor.