Ultrafiltration for Heart Surgery in Children

(ULTRA Trial)

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: IWK Health Centre

Disqualifiers: Severe hematologic, genetic syndromes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

96 Participants Needed

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Ultrafiltration for Heart Surgery in Children?

Research shows that using modified ultrafiltration (a process to remove excess fluid) during heart surgery in children can help reduce complications and improve recovery. It helps manage fluid levels and reduces harmful effects from the surgery, leading to better outcomes for young patients. ^{1 2 3 4 5}

How is the ultrafiltration treatment for heart surgery in children different from other treatments?

Ultrafiltration, including its modified forms like SBUF-SMUF, is unique because it helps reduce fluid overload and inflammation during pediatric heart surgery by filtering excess fluid and inflammatory substances from the blood, which can improve recovery and reduce complications compared to standard treatments. ^{1 2 4 5 6}

Eligibility Criteria

This trial is for children with congenital heart disease weighing between 2.5 to 15kg, who are scheduled for cardiac surgery requiring cardiopulmonary bypass. Parents or guardians must consent to participate. It excludes those over 15kg (with some exceptions), without planned CPB use, isolated ASD repair, severe blood disorders, certain genetic syndromes with immune dysfunction, immunodeficiency syndromes, and severe liver or kidney disease.

Inclusion Criteria

My child, weighing between 2.5 and 15kg, is scheduled for heart surgery with cardiopulmonary bypass.

Parent or legal substitute decision-maker informed written consent to participate in the study.

Exclusion Criteria

I do not have severe liver or kidney disease.

I have a severe blood disorder like sickle cell or hemophilia.

I have a genetic condition like DiGeorge, Trisomy 18 or 13, or Noonan syndrome.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Intra-operative Ultrafiltration

Participants undergo cardiac surgery with either high-exchange or low-exchange ultrafiltration to manage inflammation and fluid overload

1 day

Post-operative Monitoring

Participants are monitored for post-operative outcomes including cytokine levels, kidney function, and ventilation needs

7 days

Daily monitoring in ICU

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of prolonged intubation and acute kidney injury

28 days

Treatment Details

Interventions

• Ultrafiltration

Trial Overview The study tests two ultrafiltration protocols during heart surgery in kids: high-exchange (60ml/kg/hr) versus low-exchange (6ml/kg/hr). The goal is to see which better reduces inflammation from the heart-lung machine used in surgery and improves recovery outcomes.

Participant Groups

Group I: High-Exchange Ultrafiltration Experimental Treatment 1 Intervention

Subzero-Balance Simple Modified Ultrafiltration (60ml/kg/hour)

Group II: Low-Exchange Ultrafiltration Active Control 1 Intervention

Subzero-Balance Simple Modified Ultrafiltration (6ml/kg/hour)

Ultrafiltration is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Ultrafiltration for:

• Fluid overload management in pediatric cardiac surgery
• Reduction of inflammatory response in cardiac operations

Approved in Canada as Ultrafiltration for:

• Fluid overload management in pediatric cardiac surgery
• Reduction of inflammatory response in cardiac operations

Approved in European Union as Ultrafiltration for:

• Fluid overload management in pediatric cardiac surgery
• Reduction of inflammatory response in cardiac operations

Who Is Running the Clinical Trial?

IWK Health Centre

Lead Sponsor

Trials

131

Recruited

112,000+

Findings from Research

The addition of modified ultrafiltration (MUF) to conventional ultrafiltration (CUF) in pediatric cardiac surgery significantly increased post-cardiopulmonary bypass (CPB) hematocrit levels and ultrafiltration volume, based on a meta-analysis of 8 trials involving 405 patients.

However, the combination of MUF and CUF did not show a significant impact on other postoperative clinical outcomes, such as hospital stay duration or blood requirements, indicating that while MUF may improve certain hematological parameters, its overall effect on recovery metrics remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of modified ultrafiltration and conventional ultrafiltration combination on perioperative clinical outcomes in pediatric cardiac surgery: A meta-analysis. Hu, J., Li, P., Chen, X., et al.[2021]

The use of cardiopulmonary bypass (CPB) in pediatric cardiac surgery can lead to serious complications like hemodilution and inflammation, which can negatively impact recovery.

The new technique called Subzero Balance Simple Modified Ultrafiltration (SBUF-SMUF) combines continuous and non-continuous ultrafiltration methods to potentially improve recovery outcomes for infants and children undergoing surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subzero balance - simple modified ultrafiltration (SBUF-SMUF) technique for pediatric cardiopulmonary bypass. Bierer, J., Henderson, M., Stanzel, R., et al.[2022]

In a study of 120 children undergoing cavopulmonary operations, the use of modified ultrafiltration after cardiopulmonary bypass significantly reduced postoperative complications, including blood use and hospital stay.

The operative mortality rate was very low at 0.8%, indicating that modified ultrafiltration is a safe and effective intervention that improves outcomes for children with single-ventricle cardiac anomalies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified ultrafiltration reduces postoperative morbidity after cavopulmonary connection. Koutlas, TC., Gaynor, JW., Nicolson, SC., et al.[2019]

In a study of 46 pediatric patients undergoing congenital heart surgery, modified ultrafiltration (MUF) significantly improved hemodynamic status, as evidenced by increased blood pressure measurements immediately after the procedure.

MUF also reduced the duration of mechanical ventilation and the need for inotropic support compared to conventional ultrafiltration (CUF), indicating it may enhance recovery in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of combined conventional and modified ultrafiltration on mechanical ventilation and hemodynamic changes in congenital heart surgery. Ziyaeifard, M., Alizadehasl, A., Aghdaii, N., et al.[2020]

In a study of 60 newborns and infants undergoing surgery for transposition of great arteries, extended modified ultrafiltration (15 and 20 minutes) significantly increased hematocrit levels and systolic blood pressure compared to a shorter duration (10 minutes).

All groups showed similar improvements in pulmonary compliance and gas exchange, indicating that while longer modified ultrafiltration can enhance certain hemodynamic parameters, it did not significantly affect the duration of intubation or ICU stay.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of modified ultrafiltration duration on pulmonary functions and hemodynamics in newborns and infants following arterial switch operation*. Türköz, A., Tunçay, E., Balci, ŞT., et al.[2014]

In a study of 50 pediatric patients undergoing cardiac surgery, both conventional and modified ultrafiltration techniques were found to be similarly effective in removing inflammatory mediators during cardiopulmonary bypass.

Modified ultrafiltration removed significantly greater volumes of tumor necrosis factor-alpha and interleukin-6 compared to conventional methods, but overall efficacy in removing inflammatory mediators did not differ between the two techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations. Wang, MJ., Chiu, IS., Hsu, CM., et al.[2010]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of modified ultrafiltration and conventional ultrafiltration combination on perioperative clinical outcomes in pediatric cardiac surgery: A meta-analysis. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Subzero balance - simple modified ultrafiltration (SBUF-SMUF) technique for pediatric cardiopulmonary bypass. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Modified ultrafiltration reduces postoperative morbidity after cavopulmonary connection. [2019]

4. India pubmed.ncbi.nlm.nih.gov

The effect of combined conventional and modified ultrafiltration on mechanical ventilation and hemodynamic changes in congenital heart surgery. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

The effect of modified ultrafiltration duration on pulmonary functions and hemodynamics in newborns and infants following arterial switch operation*. [2014]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of ultrafiltration in removing inflammatory mediators during pediatric cardiac operations. [2010]