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

Trial Summary

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.

Is Ferumoxytol generally safe for humans?

Ferumoxytol, used as an intravenous iron product, has been associated with adverse events (unwanted side effects) in some patients, as reported in studies. It's important to discuss potential risks with your doctor, as safety can vary based on individual health conditions. ^{1 2 3 4 5}

How does the drug Ferumoxytol differ from other treatments for infant pulmonary vein stenosis?

Ferumoxytol is unique because it is primarily used as an iron replacement therapy, and its application in treating infant pulmonary vein stenosis is novel. Unlike standard treatments for pulmonary hypertension, which often involve prostacyclin or other vasodilators, Ferumoxytol's role in this condition is not well-established, making it an innovative approach. ^{6 7 8 9 10}

What is the purpose of this trial?

The purpose of this study is to better understand pediatric pulmonary vein stenosis (PVS), which is the narrowing of blood vessels that connect the lungs to the heart. PVS is a life-threatening disease without a clear cause. The investigators think patients who develop PVS have an increased Wall Shear Stress (WSS) level in the pulmonary veins, which is the force placed on the walls of the 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 possible, the investigators aim to use FcMRI to better screen patients at risk of PVS and to help guide therapy in patients with PVS.

Research Team

Ryan Callahan, MD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

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

A retrospective review of paediatric adverse drug reactions reported in Lombardy and Croatia from 2005 to 2013. [2017]

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

Adverse drug reactions: the San Juan Department of Veterans Affairs Medical Center experience. [2013]

4. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Off-Label Use of Drugs and Adverse Drug Reactions in Pediatric Units: A Prospective, Multicenter Study. [2019]

5. England 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. [2021]

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

Safety of epoprostenol and treprostinil in children less than 12 months of age. [2021]

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

The Use of Nesiritide in Children With Congenital Heart Disease. [2018]

8. Switzerland 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. [2022]

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

Transitioning From Intravenous to Subcutaneous Prostacyclin Therapy in Neonates With Severe Pulmonary Hypertension. [2020]

10. England pubmed.ncbi.nlm.nih.gov

The use of nesiritide in patients with critical cardiac disease. [2018]