Pediatric Congenital Heart Disease
Conditions
Keywords
ferumoxytol
Brief 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.
Interventions
DRUGferumoxytol
ferumoxytol as an MRI contrast agent infused over several minutes
DRUGgadofosveset
gadofosveset as an MRI contrast agent injected over several seconds
Sponsors
Paul Finn
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 6 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite Image Quality Score Among 7 Anatomical Structures. | day 1 | 1-4 image quality Likert score by an imaging expert, with 4 representing excellent image quality and 1 is non-diagnostic |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image Quality Score at Individual Anatomical Sites. | day 1 | 1-4 image quality Likert score by an imaging expert, with 4 representing excellent image quality and 1 is non-diagnostic. 1. image quality score at the aortic root. 2. image quality score at the main pulmonary artery. 3. image quality score at the coronary arteries. 4. image quality score a the out-flow tracts. 5. image quality score at the valves. 6. image quality score at the ventricular chambers. 7. image quality at the atria. |
| Incidence of Adverse Events | day 1 | Number of participants with one or more adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ferumoxytol Ferumoxytol, 4mg/kg of body weight, one time infusion of several minutes
ferumoxytol: ferumoxytol as an MRI contrast agent infused over several minutes | 14 |
| Gadofosveset gadofosveset, 0.03mmol/kg, one time bolus injection
gadofosveset: gadofosveset as an MRI contrast agent injected over several seconds | 3 |
| Total | 17 |
Baseline characteristics
| Characteristic | Gadofosveset | Total | Ferumoxytol |
|---|---|---|---|
| Age, Categorical <=18 years | 3 Participants | 17 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 3 participants | 17 participants | 14 participants |
| Sex: Female, Male Female | 2 Participants | 10 Participants | 8 Participants |
| Sex: Female, Male Male | 1 Participants | 7 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 3 |
| other Total, other adverse events | 0 / 14 | 0 / 3 |
| serious Total, serious adverse events | 0 / 14 | 0 / 3 |
Outcome results
Primary
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
Time frame: day 1
Population: Includes all participants that had successfully reconstructed images
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ferumoxytol | Composite Image Quality Score Among 7 Anatomical Structures. | 3.9 score on a scale | Standard Deviation 0.1 |
| Gadofosveset | Composite Image Quality Score Among 7 Anatomical Structures. | 2.7 score on a scale | Standard Deviation 0.2 |
Secondary
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. 1. image quality score at the aortic root. 2. image quality score at the main pulmonary artery. 3. image quality score at the coronary arteries. 4. image quality score a the out-flow tracts. 5. image quality score at the valves. 6. image quality score at the ventricular chambers. 7. image quality at the atria.
Time frame: day 1
Population: includes participants with successfully reconstructed images.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | coronary arteries | 3.8 score on a scale |
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | valves | 4 score on a scale |
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | main pulmonary artery | 3.9 score on a scale |
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | ventricular chambers | 4 score on a scale |
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | outflow tracts | 4 score on a scale |
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | atria | 4 score on a scale |
| Ferumoxytol | Image Quality Score at Individual Anatomical Sites. | aortic root | 3.8 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | atria | 2.8 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | aortic root | 3 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | main pulmonary artery | 3 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | coronary arteries | 2.5 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | outflow tracts | 2.5 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | valves | 2.5 score on a scale |
| Gadofosveset | Image Quality Score at Individual Anatomical Sites. | ventricular chambers | 2.8 score on a scale |
Secondary
Incidence of Adverse Events
Number of participants with one or more adverse events
Time frame: day 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ferumoxytol | Incidence of Adverse Events | 0 Participants |
| Gadofosveset | Incidence of Adverse Events | 0 Participants |