Feraheme As An MRI Contrast Agent For Pediatric Congenital Heart Disease
Condition: Pediatric Congenital Heart Disease
MeSH terms: Heart Diseases; Heart Defects, Congenital
Intervention: ferumoxytol; gadofosveset
Intervention description: ferumoxytol as an MRI contrast agent infused over several minutes; gadofosveset as an MRI contrast agent injected over several seconds
Intervention MeSH terms: Ferrosoferric Oxide
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 1 Day
Maximum age: 6 Years
Healthy volunteers: No
Keywords: ferumoxytol

Summary:

      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.
    

Eligibility criteria:

        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.