Ferumoxytol for Infant Pulmonary Vein Stenosis

(PVS-WSS Trial)

Recruiting at 1 trial location

Overseen By Ryan Callahan, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Hospital of Philadelphia

Must be taking: Ferumoxytol

Disqualifiers: Congenital heart disease, Iron overload, 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: 1

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to gain insights into pediatric pulmonary vein stenosis (PVS), a serious condition where the blood vessels connecting the lungs to the heart narrow. Researchers use a special MRI technique enhanced by Ferumoxytol (also known as Feraheme) to measure Wall Shear Stress (the force on the vein walls) in infants. The goal is to improve screening and treatment for infants at risk of or suffering from PVS. Infants with moderate to severe breathing problems (bronchopulmonary dysplasia) or those who have undergone specific heart repairs might be suitable for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It is best to discuss this with the study team or your doctor.

What prior data suggests that Ferumoxytol enhanced cMRI is safe for infants?

Research has shown that ferumoxytol, used in heart imaging (cardiac MRI), has undergone safety testing in several studies. Some participants experienced serious side effects, such as allergic reactions and low blood pressure. The chance of a severe allergic reaction ranged from 0.02% to 1.3% across different studies, indicating it is rare but possible. One study found that ferumoxytol caused more side effects compared to other iron products used similarly. Despite these risks, ferumoxytol has been used in children for various imaging purposes. Overall, while some risks exist, the treatment is generally considered safe when used carefully. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for infant pulmonary vein stenosis focus on surgical or catheter-based interventions to relieve vein obstruction. But Ferumoxytol offers a different approach by enhancing cardiac MRI images, which can improve the diagnosis and monitoring of this condition. Researchers are excited about Ferumoxytol because it uses iron oxide nanoparticles to create clearer, more detailed images of the heart and blood vessels. This could potentially lead to better treatment planning and outcomes for infants suffering from this serious condition.

What evidence suggests that Ferumoxytol enhanced cMRI is effective for screening and guiding therapy in pediatric pulmonary vein stenosis?

Research has shown that Ferumoxytol can improve MRI images, potentially aiding in measuring blood flow force in the pulmonary veins of infants. In this trial, participants will receive a one-time dose of Ferumoxytol before the cMRI to enhance the images. Understanding this blood flow can help identify infants at risk for pulmonary vein stenosis (PVS), a condition where the blood vessels from the lungs to the heart become dangerously narrow. This imaging method with Ferumoxytol could also assist doctors in planning treatments for PVS. Early findings suggest that using Ferumoxytol in imaging is feasible and could be a valuable tool for better understanding and managing PVS. ^{2 3 4 6 7}

Who Is on the Research Team?

Ryan Callahan, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for infants with pulmonary vein stenosis (PVS), a condition where blood vessels between the lungs and heart are narrowed. Details on specific inclusion or exclusion criteria were not provided, so it's best to contact the study team for eligibility details.

Inclusion Criteria

I am scheduled for a special MRI with a specific contrast agent.

Weight > 3 kg

I am under 18 years old.

Exclusion Criteria

I have a heart condition from birth, but it's not a minor shunt or isolated valve issue.

Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

I am allergic to ferumoxytol or have too much iron in my body.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Measurement

Participants undergo Ferumoxytol enhanced Cardiac Magnetic Resonance Imaging (FcMRI) to calculate Wall Shear Stress (WSS) in pulmonary veins

1 day

1 visit (in-person)

Follow-up

Participants are monitored for a new diagnosis of PVS and other outcomes following the imaging

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Ferumoxytol

Trial Overview The study tests if Wall Shear Stress (WSS) in infants' pulmonary veins can be measured using Ferumoxytol-enhanced Cardiac Magnetic Resonance Imaging (FcMRI). This could help identify at-risk patients and guide treatment for PVS.

How Is the Trial Designed?

Group I: Ferumoxytol enhanced cMRI Experimental Treatment 1 Intervention

A one time dose of Ferumoxytol will be administered prior to the cMRI in order to enhance the images. A dose of 4 mg/kg (max dose 510 mg) administered at a concentration of 8 mg/mL (in saline) will be used for this study. If the volume being administered is less than 6 mL, this is diluted with 3 mL of normal saline prior to administration. The drug is given over 15 minutes intravenously through a central or peripheral line. The drug is given at least 15 minutes prior to cardiac imaging.

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

The San Juan Department of Veterans Affairs Medical Center's adverse drug reactions (ADRs) program reported a significant increase in ADR reports (750%) over two years, highlighting the effectiveness of their educational campaigns and simplified reporting methods.

The most common ADRs were hypersensitivity (29.3%) and drug intoxications (19.9%), primarily linked to antibiotics and cardiovascular agents, indicating a need for targeted preventive interventions like clinical pharmacist-run clinics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions: the San Juan Department of Veterans Affairs Medical Center experience. Nazario, M., Feliú, JF., Rivera, GC.[2013]

A total of 197 adverse events (AEs) were reported among patients using various intravenous iron products, with ferumoxytol showing the highest rate of AEs at 746 per million units sold, compared to iron sucrose at 5.25 per million.

Ferumoxytol was associated with significantly higher risks of death and serious nonfatal AEs compared to iron sucrose and sodium ferric gluconate, indicating a need for caution when using this newer iron product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of rates of reported adverse events associated with i.v. iron products in the United States. Bailie, GR.[2022]

A study analyzing the US FDA Adverse Event Reporting System identified 334 adverse cardiac events linked to hydroxychloroquine in older adults, highlighting a significant risk of heart-related issues.

Strong signals of disproportionality were found for serious conditions such as restrictive cardiomyopathy and right ventricular hypertrophy, indicating a concerning association between hydroxychloroquine use and these cardiac disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of the US FDA adverse event reporting system to identify adverse cardiac events associated with hydroxychloroquine in older adults. Nishtala, PS., Gill, S., Chyou, TY.[2021]

In a study of 26 pediatric patients with critical congenital heart disease, nesiritide infusion significantly improved hemodynamic parameters, including a decrease in central venous pressure and heart rate, along with a trend towards increased urine output.

Nesiritide treatment also led to a significant reduction in serum creatinine levels and improvement in acute kidney injury stages, with notable improvements observed by day 4 of therapy, indicating its safety and efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Use of Nesiritide in Children With Congenital Heart Disease. Bronicki, RA., Domico, M., Checchia, PA., et al.[2018]

In a study of 11 children with critical congenital heart disease (CHD), nesiritide treatment led to significant improvements in heart rate and central venous pressure, indicating better hemodynamic stability.

Nesiritide was associated with a significant decrease in serum creatinine levels, suggesting improved kidney function, and 42% of patients experienced a notable improvement in their acute kidney injury stage, demonstrating its potential safety and efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of nesiritide in patients with critical cardiac disease. Bronicki, RA., Domico, M., Checchia, PA., et al.[2018]

A retrospective study of infant intravenous prostacyclin use in a pediatric hospital showed that it was generally well tolerated for treating severe pulmonary hypertension, with some adverse events like hypotension and pain, but no serious complications directly linked to the drug.

While the study could not definitively evaluate the efficacy of prostacyclin due to the complexity of cases, it noted several positive outcomes, including 6 resolutions of pulmonary hypertension and transitions to oral medications, suggesting potential benefits in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of epoprostenol and treprostinil in children less than 12 months of age. McIntyre, CM., Hanna, BD., Rintoul, N., et al.[2021]

In a study involving 5 neonates with persistent pulmonary hypertension, transitioning from intravenous epoprostenol to intravenous and subcutaneous treprostinil was successful, with all patients surviving to hospital discharge.

The transition was well tolerated with minimal adverse effects, indicating that high-dose rapid switching between these therapies can be a safe and effective treatment option for severe pulmonary hypertension in neonates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transitioning From Intravenous to Subcutaneous Prostacyclin Therapy in Neonates With Severe Pulmonary Hypertension. Turbenson, MN., Radosevich, JJ., Manuel, V., et al.[2020]

A total of 9,175 adverse drug reaction (ADR) reports were analyzed from Lombardy and 2,457 from Croatia, with the highest number of reports coming from children aged 2-11 years in both regions.

Serious ADRs were reported in 13.2% of cases in Lombardy and 40.3% in Croatia, with very low fatality rates of 0.09% and 0.12%, respectively, indicating a need for careful monitoring of pediatric drug use, especially for common medications like penicillins and anti-inflammatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A retrospective review of paediatric adverse drug reactions reported in Lombardy and Croatia from 2005 to 2013. Carnovale, C., Gentili, M., Matacena, M., et al.[2017]

In a one-year pharmacovigilance study involving 5,060 pediatric patients in Sicily, 8.97% received at least one off-label drug, with newborns being the most affected group (56.2%).

Patients treated with off-label medications had a significantly higher risk of adverse drug reactions (7.3%) compared to those on on-label medications (1.2%), highlighting the need for careful monitoring in pediatric care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label Use of Drugs and Adverse Drug Reactions in Pediatric Units: A Prospective, Multicenter Study. Pratico, AD., Longo, L., Mansueto, S., et al.[2019]

A premature infant with severe pulmonary hypertension (PH) and bronchopulmonary dysplasia (BPD) showed significant improvement after being treated with off-label oral selexipag, which helped reduce right ventricular systolic pressure and allowed for successful weaning from mechanical ventilation and other medications.

This case suggests that selexipag, an oral prostacyclin mimetic, may be a beneficial early treatment option for chronic pulmonary hypertension in infants, as evidenced by the patient's stable condition and reduced pulmonary pressures after initiating therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Rescue treatment with add-on selexipag in a preterm infant with suprasystemic pulmonary hypertension, pulmonary capillary hemangiomatosis, and isolated pulmonary vein stenosis. Hasan, H., Hysko, K., Jack, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06440408

Calculating Wall Shear Stress in Infant Pulmonary Veins This study will determine if WSS can be calculated in the pulmonary veins of infants using Ferumoxytol enhanced Cardiac Magnetic Resonance Imaging (FcMRI). If ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5373922/

Feasibility of Ferumoxytol-Enhanced Neonatal and Young ... Ferumoxytol can be administered hours before the actual MRI exam. The patient can then be swaddled and possibly fed for the MRI scan. Also, in ...

3. withpower.com withpower.com/trial/phase-1-stenosis-pulmonary-vein-8-2024-3bfc0

Ferumoxytol for Infant Pulmonary Vein Stenosis A total of 197 adverse events (AEs) were reported among patients using various intravenous iron products, with ferumoxytol showing the highest rate of AEs at ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06440408?term=AREA%5BBasicSearch%5D(ferumoxytol)%20AND%20AREA%5BStdAge%5D(CHILD)&rank=6

Calculating Wall Shear Stress in Infant Pulmonary Veins This study will determine if WSS can be calculated in the pulmonary veins of infants using Ferumoxytol enhanced Cardiac Magnetic Resonance Imaging (FcMRI). If ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11442208/

Hemodynamic Assessment of Infants With Congenital ... We demonstrate 3 cases in infants with congenital heart disease where 4D flow analysis greatly affected decisions on the type of surgical repair.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4854636/

Safety and Technique of Ferumoxytol Administration for MRI Serious adverse events included hypersensitivity (2,4) and hypotension (4). The reported rates of anaphylaxis ranged from 0.02% with 2/8666 (4) to 1.3% with 1/ ...

7. pubs.rsna.org pubs.rsna.org/doi/full/10.1148/ryct.210323

Contrast-enhanced MR Angiography without Gadolinium ... In recent years, the safety of ferumoxytol for use in pediatric populations has been assessed across many studies for evaluation of lymph ...