High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery (ULTRA)

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

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.

Study Overview

• Status: Completed
• Conditions: Congenital Heart Disease
• Intervention / Treatment: Procedure: Ultrafiltration

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • IWK Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-Exchange Ultrafiltration; Subzero-Balance Simple Modified Ultrafiltration (60ml/kg/hour)	Procedure: Ultrafiltration; 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.
Active Comparator: Low-Exchange Ultrafiltration; Subzero-Balance Simple Modified Ultrafiltration (6ml/kg/hour)	Procedure: Ultrafiltration; 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-Reactive Protein Concentrations		Measured at 1 day
Loop Diuretic Use	Total loop diuretic (mg/kg), measured in furosemide equivalents, during the first 7 post-operative days.	Up to 7 days
Vasoactive Inotrope Score	Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.	Up to 5 days
Ventilation Index	Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.	Up to 5 days
Oxygenation Index	Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.	Up to 5 days
Ventilation Time		Up to 28 days
Ventilator Free Days		Up to 28 days
Low Cardiac Output Syndrome	Defined by any one of the following within the first 72 post-operative hours: Lactate > 4mM with oxygen extraction >35% (SaO2 - ScvO2/ SaO2); VIS > 15.0 with oxygen extraction >35% (SaO2 - ScvO2/ SaO2); Mechanical circulatory support requirement	Up to 3 days
Vasoplegic Shock	Defined by any one of the following with the first 72 post-operative hours: Lactate > 4mM with oxygen extraction <25% (SaO2 - ScvO2/ SaO2); VIS > 15.0 with oxygen extraction <25% (SaO2 - ScvO2/ SaO2)	Up to 3 days
Inotrope Dependence	Vasoactive-inotrope score at 48 hours equal to or greater than that at ICU admission.	Up to 2 days
Inotrope Free Days		Up to 28 days
Composite Outcome of mechanical circulatory support, acute renal failure, prolonged intubation and operative mortality.		Up to 30 days
Cytokine Concentration (Patient Plasma)	C3, C3a, C3b, C5, C5a, IL-1, IL1-Ra, IL-6, IL-10, TNF, CXCL-8 among others. The final selection of mediators will be subject to final pilot study results and assay availability. Taken at baseline, 0 hours and 24 hours after CPB.	Up to 1 day
Peak Vasoactive-Inotrope Score		Up to 5 days
Peak Ventilation Index		Up to 5 days
Peak Oxygenation Index		Up to 5 days
Prolonged Intubation	Mechanical ventilation for more than 7 days	Up to 28 days
Inotrope Time		Up to 28 days
Acute Kidney Injury	KDIGO Criteria	Up to 28 days
ICU Length of Stay		Up to 30 days
Hospital Length of Stay		Up to 60 days
Haptoglobin (Plasma)		Up to 1 day
Complete blood count		Up to 5 days
Lactate	Measured by arterial blood gas (mM)	Up to 5 days
Creatinine	Blood Concentration (uM)	Up to 5 days
Vasoactive-Ventilation Renal Score	Taken in time series at ICU admission, 12, 24, 36, 48, 72, 96 and 120 hours.	Up to 5 days

Collaborators and Investigators

• Sponsor: IWK Health Centre

Publications and helpful links

General Publications

• Bierer J, Stanzel R, Henderson M, Sett S, Horne D. Ultrafiltration in Pediatric Cardiac Surgery Review. World J Pediatr Congenit Heart Surg. 2019 Nov;10(6):778-788. doi: 10.1177/2150135119870176.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): May 21, 2025
• Study Completion (Actual): May 21, 2025

Study Registration Dates

• First Submitted: May 30, 2021
• First Submitted That Met QC Criteria: June 3, 2021
• First Posted (Actual): June 10, 2021

Study Record Updates

• Last Update Posted (Actual): May 25, 2025
• Last Update Submitted That Met QC Criteria: May 21, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital
• Other Study ID Numbers: IWKHealthC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No