Feraheme As An MRI Contrast Agent For Pediatric Congenital Heart Disease

Study Overview
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Brief Summary
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The standard clinical cardiovascular MRI practice for children with CHD frequently involves the use of gadolinium-based contrast agents (GBCA) to enhance tissue contrast. Most GBCAs are small molecules that quickly cross the capillary wall and access the interstitial space, a process which diminishes the signal contrast between blood vessels and surrounding tissue. Therefore, these types of GBCA are most useful for first-pass MR angiography, wherein the images are acquired quickly during the initial 15-30 seconds post-injection when the GBCA concentration is much higher in the arteries than in the interstitial space. For young children with complex CHD, the stringent requirements for high spatial resolution, and the need for cardiac gating and good blood-myocardium contrast in order to provide detailed evaluation of intracardiac structures are not compatible with conventional GBCA-based first-pass MR angiography. Even with Ablavar® (gadofosveset trisodium), an FDA approved GBCA with longer intravascular half-life than other GBCAs, cardiac-gated Ablavar®-enhanced MRI may be insufficient for young children with CHD based on our institutional experience and on data from the literature; there remains diminished blood-tissue contrast during the high-resolution cardiac-gated MRI. Furthermore, there have been safety concerns regarding gadolinium deposition in brain tissues after repeated GBCA exposure as well as concerns of nephrogenic systemic fibrosis (NSF) associated with GBCA injection in young children < 2 years old who may have immature renal function. The long-term health consequences of these effects in the pediatric population are unclear. For the above reasons, we seek to study the diagnostic imaging effectiveness of Feraheme (Feraheme®), an FDA-approved drug for parenteral iron supplementation, as an MRI contrast agent in children with CHD. Although Feraheme® has been approved for the treatment of iron deficiency anemia secondary to renal disease, Feraheme® has been used as an off-label MRI contrast agent at select medical centers.

Official Title
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Feraheme As An MRI Contrast Agent For Pediatric Congenital Heart Disease

Conditions
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Pediatric Congenital Heart Disease

Intervention / Treatment
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* Drug: ferumoxytol
* Drug: gadofosveset


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female pediatric patients of all ethnicities (age newborn to 6 years) with known or suspected CHD with inconclusive echocardiographic exams and are referred for cardiovascular MRI for further evaluation of cardiac anatomy and function. Written informed consent obtained from subject's legal representative/guardian(s) and ability for subject to comply with the requirements of the study Exclusion Criteria: Standard clinical contraindications to MRI, including subjects with cochlear implants and implanted cardiac devices Subjects with past or current diagnosis of iron overload due to hereditary hemochromatosis or other causes (for subjects receiving Feraheme injection only). Subjects with known hypersensitivity or allergy to iron oxide particles. Subjects with renal insufficiency defined as estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73m2 (for subjects receiving Ablavar injection only). Subjects who are critically ill at the time of MRI and for whom the period of general anesthesia and separation from the critical care nursery or intensive care unit poses added risk as deemed by referring cardiologists, cardiac surgeons or the managing radiologist (for Part II only). Other medical conditions, in the judgment of the clinician investigator, that would increase the risks to the child related to participation in the study.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ferumoxytol<br>Ferumoxytol, 4mg/kg of body weight, one time infusion of several minutes | Drug: ferumoxytol<br>* ferumoxytol as an MRI contrast agent infused over several minutes<br>* Other names: Feraheme;|
| Active Comparator: gadofosveset<br>gadofosveset, 0.03mmol/kg, one time bolus injection | Drug: gadofosveset<br>* gadofosveset as an MRI contrast agent injected over several seconds<br>* Other names: Ablavar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Image Quality Score Among 7 Anatomical Structures. | 1-4 image quality Likert score by an imaging expert, with 4 representing excellent image quality and 1 is non-diagnostic | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Image Quality Score at Individual Anatomical Sites. | 1-4 image quality Likert score by an imaging expert, with 4 representing excellent image quality and 1 is non-diagnostic. image quality score at the aortic root. image quality score at the main pulmonary artery. image quality score at the coronary arteries. image quality score a the out-flow tracts. image quality score at the valves. image quality score at the ventricular chambers. image quality at the atria. | day 1 | 
| Incidence of Adverse Events | Number of participants with one or more adverse events | day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ferumoxytol