Magnetic Resonance Imaging of the Liver in Children 0-2 Months of Age With an Intravenous Injection of Eovist/Primovist Which is a Contrast Agent

Study Overview
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Brief Summary
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This is an open-label, multi-center study involving babies 0-2 months of age who have liver problems (pathology) and need to have their liver and possibly, the bile ducts imaged using magnetic resonance imaging and injection of a contrast agent (dye). This agent is called Eovist. It has been marketed since 2004 and used in many countries all over the world. The baby will have blood tests before and after the imaging is done to make sure that there are no unexpected findings before and after the imaging. Also 3 blood samples up to 8 hours after the injection will be obtained in order to measure how much of the dye is in the blood. The baby will have an intravenous line which can be used for the blood samples and will not need to be stick for the blood samples. Several radiologists will evaluate the images. The family doctor will be contacted to find out what was the diagnosis and treatment after the results of the MRI were known. Six months after the study, the parent(s)/legal guardian(s) will be contacted to make sure the that baby did not have any problems, especially with the skin, joints and eyes.

Detailed Description
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In order to minimize bias in assessment of the images, blinded reading of the MR images will be performed by 2 blinded readers. The blinded readers will be independent board-certified pediatric radiologists who have no knowledge about the subjects and are not affiliated with any of the clinical sites.

Official Title
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Open-label, Multi-center Study to Evaluate the Safety, Efficacy, and Plasma Gadolinium Concentrations After an Intravenous Injection of 0.1 mL/kg Body Weight Eovist/Primovist for Enhanced Magnetic Resonance Imaging (MRI) of the Liver in Children 0 to 2 Months of Age

Conditions
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Magnetic Resonance Imaging

Intervention / Treatment
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* Drug: Gadoxetate disodium (Eovist/Primovist, BAY86-4873)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 0-2 months (must be gestational age 37 to 41 weeks) Scheduled to undergo routine contrast-enhanced liver MRI Able to comly with the study procedures Exclusion Criteria: Scheduled for any intervention (except lumbar puncture and bone marrow aspiration) during the study period If receiving chemotherapy, may have a change in treatment during the study period Contraindication for MRI Renal insufficiency (estimated glomerular filtration rate < 80% of age-adjusted normal mean value using the Schwartz formula) Acute renal failure Clinically relevant abnormal laboratory parameter, ie, greater than 3 times the upper limit of the normal range, in particular, liver enzymes and renal function. (Note: if elevations in liver enzyme levels are consistent with the underlying hepatobiliary disease, then the subject may be enrolled.)

Ages Eligible for Study
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Maximum Age: 2 Months

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gadoxetate disodium (Eovist/Primovist, BAY86-4873)<br>Participants to receive single dose of Eovist/Primovist as a manual injection at a dose of 0.1 milliliter per kilogram (mL/kg) body weight (BW) (0.025 millimole [mmol]/kg BW), followed by a flush of at least 5 mL saline (sodium chloride 0.9 percent [%] solution) manually. | Drug: Gadoxetate disodium (Eovist/Primovist, BAY86-4873)<br>* Participants to receive single dose of Eovist/Primovist as a manual injection at a dose of 0.1 milliliter per kilogram (mL/kg) body weight (BW) (0.025 millimole [mmol]/kg BW), followed by a flush of at least 5 mL saline (sodium chloride 0.9 percent [%] solution) manually.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Additional Diagnostic Information From Combined (Pre-contrast And Post-contrast) Images Compared With Pre-contrast Images | Additional diagnostic information such as better delineation of the border of the lesion, better definition of the internal morphology of the lesion, better characterization of the lesion, better definition of the location of the lesion, better assessment of the communication of the lesion with respect to the biliary system obtained from the combined magnetic resonance (MR) images compared with pre-contrast MR images. Number of subjects with additional diagnostic information were recorded and analyzed. | Images were taken pre-injection and post-injection (within about 15 minutes) | 
| Number of Subjects With Adverse Events | An adverse event (AE) was any untoward medical occurrence that is, any unfavorable and unintended sign (including abnormal laboratory findings), symptom or disease in a subject or clinical investigation subject after providing written informed consent for participation in the study. | From the signing of the informed consent form until the 6 month post MRI follow-up | 
| Number of Subjects With Serious Adverse Events | An serious adverse events (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | From the signing of the informed consent form until the 6 month post MRI follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Lesions Detected for the Pre-contrast Images |  | Images were taken pre-injection | 
| Number of Lesions Detected for the Combined Images |  | Images were taken pre-injection and post-injection (within about 15 minutes) | 
| Contrast Enhancement of the Liver for the Combined Images Assessed by Yes or no Question |  | Images were taken pre-injection and post-injection (within about 15 minutes) | 
| Contrast Enhancement of the Biliary System for the Combined Images Assessed by Yes or no Question | Biliary system included Gall bladder Cystic duct Common bile duct Right main bile duct Left main bile duct | Images were taken pre-injection and post-injection (within about 15 minutes) | 
| Visualization of the Biliary System for the Pre-contrast and Combined Images Assessed by Yes or no Question |  | Images were taken pre-injection and post-injection (within about 15 minutes) | 
| Change in Diagnosis for the Combined Images Compared With Precontrast Images | Diagnosis based on the pre-contrast images will be indicated. If there is a change in the diagnosis based on the combined images, then the combined images diagnosis will be recorded. | Images were taken pre-injection and post-injection (within about 15 minutes) | 
| Diagnostic Confidence for the Pre-contrast and Combined Images Assessed by Yes or no Question | Diagnostic confidence was classified as not confident (No), confident (Yes), very confident (Yes). | Images were taken pre-injection and post-injection (within about 15 minutes) |