Clinical trial NCT04920643: High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery
Official title: High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery (ULTRA): A Canadian Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Congenital Heart Disease
Lead sponsor: IWK Health Centre
Sponsor class: OTHER
First posted: 2021-06-10
Enrollment: 104
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Peak Vasoactive-Ventilation Renal Score
timeFrame: Up to 5 days
Secondary outcomes:
measure: Vasoactive Inotrope Score
timeFrame: Up to 5 days
measure: Ventilation Index
timeFrame: Up to 5 days
measure: Oxygenation Index
timeFrame: Up to 5 days
measure: Ventilation Time
timeFrame: Up to 28 days
measure: Ventilator Free Days
timeFrame: Up to 28 days
measure: Low Cardiac Output Syndrome
timeFrame: Up to 3 days
measure: Vasoplegic Shock
timeFrame: Up to 3 days
measure: Inotrope Dependence
timeFrame: Up to 2 days
measure: Inotrope Free Days
timeFrame: Up to 28 days
measure: C-Reactive Protein Concentrations
timeFrame: Measured at 1 day
measure: Composite Outcome of mechanical circulatory support, acute renal failure, prolonged intubation and operative mortality.
timeFrame: Up to 30 days
measure: Cytokine Concentration (Patient Plasma)
timeFrame: Up to 1 day
measure: Loop Diuretic Use
timeFrame: Up to 7 days
measure: Peak Vasoactive-Inotrope Score
timeFrame: Up to 5 days
measure: Peak Ventilation Index
timeFrame: Up to 5 days
measure: Peak Oxygenation Index
timeFrame: Up to 5 days
measure: Prolonged Intubation
timeFrame: Up to 28 days
measure: Inotrope Time
timeFrame: Up to 28 days
measure: Acute Kidney Injury
timeFrame: Up to 28 days
measure: ICU Length of Stay
timeFrame: Up to 30 days
measure: Hospital Length of Stay
timeFrame: Up to 60 days
measure: Haptoglobin (Plasma)
timeFrame: Up to 1 day
measure: Complete blood count
timeFrame: Up to 5 days
measure: Lactate
timeFrame: Up to 5 days
measure: Creatinine
timeFrame: Up to 5 days
measure: Vasoactive-Ventilation Renal Score
timeFrame: Up to 5 days
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: IWK Health Centre
state: Nova Scotia
Study officials:
References:
citation: 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.