Congenital Heart DiseaseULTRANCT04920643
High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery
A study testing Ultrafiltration in people with Congenital Heart Disease, run by IWK Health Centre at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Congenital Heart Disease
- What is being tested?
- Ultrafiltration
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteCanada
- Study dates
- 28 Sep 2021to 21 May 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Congenital Heart Disease
- Being tested
- Ultrafiltration
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UltrafiltrationProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| High-Exchange Ultrafiltration | Experimental | Subzero-Balance Simple Modified Ultrafiltration (60ml/kg/hour) Receives: Procedure: Ultrafiltration |
| Low-Exchange Ultrafiltration | Active comparator | Subzero-Balance Simple Modified Ultrafiltration (6ml/kg/hour) Receives: Procedure: Ultrafiltration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak Vasoactive-Ventilation Renal Score
Measured: Up to 5 days
Secondary outcomes (26)
Vasoactive Inotrope Score
Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.
Measured: Up to 5 days
Ventilation Index
Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.
Measured: Up to 5 days
Oxygenation Index
Taken in time series at ICU admission, 0, 12, 24, 36, 48, 72, 96 and 120 hours.
Measured: Up to 5 days
Ventilation Time
Measured: Up to 28 days
Ventilator Free Days
Measured: 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
Measured: 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)
Measured: Up to 3 days
Inotrope Dependence
Vasoactive-inotrope score at 48 hours equal to or greater than that at ICU admission.
Measured: Up to 2 days
Inotrope Free Days
Measured: Up to 28 days
C-Reactive Protein Concentrations
Measured: Measured at 1 day
Composite Outcome of mechanical circulatory support, acute renal failure, prolonged intubation and operative mortality.
Measured: 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.
Measured: Up to 1 day
Loop Diuretic Use
Total loop diuretic (mg/kg), measured in furosemide equivalents, during the first 7 post-operative days.
Measured: Up to 7 days
Peak Vasoactive-Inotrope Score
Measured: Up to 5 days
Peak Ventilation Index
Measured: Up to 5 days
Peak Oxygenation Index
Measured: Up to 5 days
Prolonged Intubation
Mechanical ventilation for more than 7 days
Measured: Up to 28 days
Inotrope Time
Measured: Up to 28 days
Acute Kidney Injury
KDIGO Criteria
Measured: Up to 28 days
ICU Length of Stay
Measured: Up to 30 days
Hospital Length of Stay
Measured: Up to 60 days
Haptoglobin (Plasma)
Measured: Up to 1 day
Complete blood count
Measured: Up to 5 days
Lactate
Measured by arterial blood gas (mM)
Measured: Up to 5 days
Creatinine
Blood Concentration (uM)
Measured: Up to 5 days
Vasoactive-Ventilation Renal Score
Taken in time series at ICU admission, 12, 24, 36, 48, 72, 96 and 120 hours.
Measured: Up to 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2021
- Study start28 Sep 2021
- Primary completion21 May 2025
- Study completion21 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- IWK Health Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. David Horne, IWK Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04920643
- Sponsor's protocol ID
- IWKHealthC
- Acronym
- ULTRA
- Status last verified
- May 2025
- First submitted
- 30 May 2021
- Last updated
- 25 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 31701831Bierer JD, Stanzel R, Henderson M, Krmpotic K, Andreou P, Marshall JS, Sapp J, Horne D. High-Exchange Ultrafiltration to Enhance Recovery After Pediatric Cardiac Surgery: The ULTRA Randomized Controlled Trial. Ann Thorac Surg. 2026 May;121(5):1158-1167. doi: 10.1016/j.athoracsur.2026.01.006. Epub 2026 Jan 27.
PubMed 41611197Bierer J, Stanzel R, Henderson M, Krmpotic K, Andreou P, Marshall JS, Sapp J, Horne D. High-exchange ULTrafiltration to enhance recovery after paediatric cardiac surgery (ULTRA): study protocol for a Canadian double-blinded randomised controlled trial. BMJ Open. 2024 Aug 28;14(8):e080597. doi: 10.1136/bmjopen-2023-080597.
PubMed 39209495
Study at a glance
From the registry record, last updated by the sponsor on 25 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-exchange ULTrafiltration to Enhance Recovery After Pediatric Cardiac Surgery (ULTRA): A Canadian Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04920643
- Acronym / sponsor ID
- ULTRA / IWKHealthC
- Conditions
- Congenital Heart Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- IWK Health CentreUniversity, hospital or other
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 21 May 2025 (actual)
- Study completion
- 21 May 2025 (actual)
- First posted
- 10 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High-Exchange Ultrafiltration | Experimental | Procedure: UltrafiltrationSubzero-Balance Simple Modified Ultrafiltration (60ml/kg/hour) |
| Low-Exchange Ultrafiltration | Active comparator | Procedure: UltrafiltrationSubzero-Balance Simple Modified Ultrafiltration (6ml/kg/hour) |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UltrafiltrationUltrafiltration is used during cardiac surgery with cardiopulmonary bypass to remove both fluid and small molecules such as inflammatory cytokines from the patient's circulation. | Procedure or surgery | High-Exchange Ultrafiltration, Low-Exchange Ultrafiltration |
Primary outcome
Peak Vasoactive-Ventilation Renal Score
Time frame: Up to 5 days
26 secondary outcomes
Vasoactive Inotrope Score
Time frame: Up to 5 days
Ventilation Index
Time frame: Up to 5 days
Oxygenation Index
Time frame: Up to 5 days
Ventilation Time
Time frame: Up to 28 days
Ventilator Free Days
Time frame: Up to 28 days
Low Cardiac Output Syndrome
Time frame: Up to 3 days
Vasoplegic Shock
Time frame: Up to 3 days
Inotrope Dependence
Time frame: Up to 2 days
Inotrope Free Days
Time frame: Up to 28 days
C-Reactive Protein Concentrations
Time frame: Measured at 1 day
Composite Outcome of mechanical circulatory support, acute renal failure, prolonged intubation and operative mortality.
Time frame: Up to 30 days
Cytokine Concentration (Patient Plasma)
Time frame: Up to 1 day
Loop Diuretic Use
Time frame: Up to 7 days
Peak Vasoactive-Inotrope Score
Time frame: Up to 5 days
Peak Ventilation Index
Time frame: Up to 5 days
Peak Oxygenation Index
Time frame: Up to 5 days
Prolonged Intubation
Time frame: Up to 28 days
Inotrope Time
Time frame: Up to 28 days
Acute Kidney Injury
Time frame: Up to 28 days
ICU Length of Stay
Time frame: Up to 30 days
Hospital Length of Stay
Time frame: Up to 60 days
Haptoglobin (Plasma)
Time frame: Up to 1 day
Complete blood count
Time frame: Up to 5 days
Lactate
Time frame: Up to 5 days
Creatinine
Time frame: Up to 5 days
Vasoactive-Ventilation Renal Score
Time frame: Up to 5 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 May 2025.
- Background: PubMed 31701831Bierer 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.
- Derived from this study: PubMed 41611197Bierer JD, Stanzel R, Henderson M, Krmpotic K, Andreou P, Marshall JS, Sapp J, Horne D. High-Exchange Ultrafiltration to Enhance Recovery After Pediatric Cardiac Surgery: The ULTRA Randomized Controlled Trial. Ann Thorac Surg. 2026 May;121(5):1158-1167. doi: 10.1016/j.athoracsur.2026.01.006. Epub 2026 Jan 27.
- Derived from this study: PubMed 39209495Bierer J, Stanzel R, Henderson M, Krmpotic K, Andreou P, Marshall JS, Sapp J, Horne D. High-exchange ULTrafiltration to enhance recovery after paediatric cardiac surgery (ULTRA): study protocol for a Canadian double-blinded randomised controlled trial. BMJ Open. 2024 Aug 28;14(8):e080597. doi: 10.1136/bmjopen-2023-080597.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ultrafiltration in people with Congenital Heart Disease, run by IWK Health Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak Vasoactive-Ventilation Renal Score (time frame: Up to 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04920643, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 May 2025.