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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to improve recovery after heart surgery in children with congenital heart disease. The focus is on using ultrafiltration during surgery to remove excess fluids and reduce inflammation caused by the heart-lung machine. Researchers are comparing two different ultrafiltration rates to determine which is most effective. Children weighing between 2.5 and 15 kg who are scheduled for heart surgery using the heart-lung machine may be suitable candidates for this trial. The goal is to enhance recovery and health outcomes for these young patients. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could significantly improve surgical outcomes for children.

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 prior data suggests that ultrafiltration is safe for children undergoing heart surgery?

Research has shown that ultrafiltration is commonly used in children's heart surgeries to manage inflammation and excess fluid caused by the heart-lung machine. Over 90% of children's heart centers use some form of this process, which removes extra fluids and inflammatory substances from the blood during surgery.

Although ultrafiltration is widely used, researchers are still studying the safety of different speeds of this process, specifically high-exchange and low-exchange methods. High-exchange ultrafiltration removes more fluid quickly, while low-exchange does so more slowly.

Studies have not found clear evidence of serious side effects for either method. However, because ultrafiltration is frequently used in heart surgeries, it is generally considered safe. Ongoing research aims to determine the best ultrafiltration speed to improve recovery for children after heart surgery, balancing effectiveness and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Ultrafiltration approach in heart surgery for children because it offers a new method to manage fluid balance during surgery. Unlike traditional methods that rely on diuretics or fluid restriction, this technique uses a filtration process to remove excess fluid directly from the blood. The two different ultrafiltration rates being tested—low-exchange and high-exchange—could provide tailored options for different patient needs, potentially improving recovery and outcomes. By directly targeting fluid overload without the side effects of medications, this method could enhance safety and efficiency in pediatric heart surgeries.

What evidence suggests that this trial's ultrafiltration protocols could be effective for heart surgery in children?

Research has shown that using ultrafiltration during heart surgery in children helps remove excess fluids and filters out substances that cause inflammation. This is crucial because inflammation from surgery can harm the body and complicate recovery. In this trial, participants will be assigned to different ultrafiltration methods. Studies have found that a special type of ultrafiltration, called modified ultrafiltration, improves heart function, reduces fluid buildup, and decreases bleeding problems. One arm of this trial will use a faster method, known as high-exchange ultrafiltration, which may further enhance recovery by reducing complications like kidney injury and low heart output. This approach aims to make recovery smoother for children after heart surgery. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11367393/

High-exchange ULTrafiltration to enhance recovery after ... Ultrafiltration has been used during paediatric cardiac surgery since the 1990s, primarily to remove excess volume and prevent tissue oedema.

2. clinicaltrials.gov clinicaltrials.gov/show/NCT04920643

High-exchange ULTrafiltration to Enhance Recovery After ... 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 ...

3. researchgate.net researchgate.net/publication/383525544_High-exchange_ULTrafiltration_to_enhance_recovery_after_paediatric_cardiac_surgery_ULTRA_study_protocol_for_a_Canadian_double-blinded_randomised_controlled_trial

(PDF) High-exchange ULTrafiltration to enhance recovery ... Secondary clinical outcomes include acute kidney injury, ventilator-free days, inotrope-free days, low cardiac output syndrome, mechanical ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34142611/

Subzero balance: simple modified ultrafiltration (SBUF ... Intra-operative ultrafiltration has been used for decades to ameliorate these harmful effects. The novel combination of a continuous and non- ...

5. journals.sagepub.com journals.sagepub.com/doi/10.1177/2150135119870176

Ultrafiltration in Pediatric Cardiac Surgery Review Modified ultrafiltration significantly promotes improved myocardial function, reduction in fluid overload, and reduced bleeding and transfusion complications.

6. semanticscholar.org semanticscholar.org/paper/258f9caa71018a81da5f413beb3fb59a862d3f08

High-exchange ULTrafiltration to enhance recovery after ... High-exchange ULTrafiltration to enhance recovery after paediatric cardiac surgery (ULTRA): study protocol for a Canadian double-blinded randomised controlled ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04920643/high-exchange-ultrafiltration-to-enhance-recovery-after-pediatric-cardiac-surgery?q=ultrafiltration

High-exchange ULTrafiltration to Enhance Recovery After ... The expected data and results could be immediately applicable to improve recovery after heart surgery for infants and children across Canada ...