High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery

Study Overview
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Brief Summary
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Malformations of the heart are common; 1.35 million infants are born each year with congenital heart disease. Many of these defects carry a considerable threat to the individual's quality of life as well as survival. Along with focused medical management, surgical repair remains a standard of care for more than 25,000 infants and children each year in the United States and Canada. The care of individuals with congenital heart disease is highly complex and has significant risks of morbidity and mortality. Most cardiac operations require the use of cardiopulmonary bypass (CPB, also known as the heart-lung machine) to safely access the inner chambers of the heart. CPB itself has been well documented to cause significant inflammation and hemodilution as the individual's blood is passed through a foreign circuit. This inflammatory response can lead to fluid overload, distributive shock and potential end-organ dysfunction in the heart, lungs, kidneys, brain, liver or bowels. These organ dysfunctions may culminate in post-operative low cardiac output syndrome (LCOS), prolonged ventilation time, prolonged intensive care unit (ICU) stay and can contribute to mortality. Dampening the inflammatory response from CPB has been a focus of research interest for years. Intra-operative ultrafiltration has been used to remove excess fluids and filter off inflammatory cytokines during cardiac operations. Over 90% of children's heart centers in the world utilize some form of ultrafiltration (mostly some form of modified ultrafiltration), but there are wide variations in published ultrafiltration protocols (none of which are combination SBUF-SMUF in children). Ultimately, this project seeks to provide high-quality evidence that the immunologic and clinical effects of combination SBUF-SMUF are rate dependent. Therefore, a randomized study directly comparing a high-exchange SBUF-SMUF (60ml/kg/hr) and a low-exchange SBUF-SMUF (6ml/kg/hr) can identify which is the optimal ultrafiltration protocol to enhance post-operative clinical outcomes for this patient population. The expected data and results could be immediately applicable to improve recovery after heart surgery for infants and children across Canada and the rest of the world at large.

Official Title
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High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery (ULTRA): A Randomized Controlled Trial

Conditions
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Congenital Heart Disease

Intervention / Treatment
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* Procedure: Ultrafiltration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Congenital heart patients (2.5 - 15kg) have consented for a planned cardiac surgery procedure requiring cardiopulmonary bypass. Parent or legal substitute decision-maker informed written consent to participate in the study. Exclusion Criteria: Patient or family refusal to participate. Patient over 15kg (Fontan or Glenn patients will be considered up to 18kg) No planned use of cardiopulmonary bypass Isolated ASD repair Known severe hematologic abnormality such as sick cell anemia, thalassemia, haemophilia A or B, von Willebrand disease or other. Known genetic syndrome with severe neurologic or multi-organ abnormalities and immune dysfunction such as DiGeorge Syndrome, Trisomy 18 or 13, Noonan syndrome. (Trisomy 21 may be included in the study). Known immunodeficiency syndrome or bone marrow pathology. Severe liver or renal disease.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High-Exchange Ultrafiltration<br>Subzero-Balance Simple Modified Ultrafiltration (60ml/kg/hour) | Procedure: Ultrafiltration<br>* Ultrafiltration is used during cardiac surgery with cardiopulmonary bypass to remove both fluid and small molecules such as inflammatory cytokines from the patient's circulation.<br>|
| Active Comparator: Low-Exchange Ultrafiltraiton<br>Subzero-Balance Simple Modified Ultrafiltration (6ml/kg/hour) | Procedure: Ultrafiltration<br>* Ultrafiltration is used during cardiac surgery with cardiopulmonary bypass to remove both fluid and small molecules such as inflammatory cytokines from the patient's circulation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Vasoactive-Ventilation Renal Score |  | Up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vasoactive Inotrope Score |  | Up to 5 days | 
| Ventilation Index |  | Up to 5 days | 
| Oxygenation Index |  | Up to 5 days | 
| Ventilation Time |  | Up to 30 days | 
| Ventilator Free Days |  | Up to 30 days | 
| Low Cardiac Output Syndrome | Pre-specified criteria | Up to 3 days | 
| Vasoplegic Shock | Pre-specified criteria | Up to 3 days | 
| Inotrope Dependence | Pre-specified criteria | Up to 2 days | 
| Inotrope Free Days |  | Up to 30 days | 
| C-Reactive Protein Concentrations |  | Measured at 1 day | 
| Composite Outcome of mechanical circulatory support, acute renal failure, prolonged intubation and death within 30 days. | Pre-specified criteria | Up to 30 days | 
| Cytokine Concentration | Plasma concentrations measured by Luminex. (specific cytokines to be selected based on Pilot study results) | Up to 1 day |