Safety and Efficacy Evaluation of DOTAREM® in MRI of Central Nervous System (CNS) Lesions

Study Overview
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Brief Summary
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The purpose of this study is to look at the safety (what are the side effects)and efficacy (how well does it work) of Dotarem® when used in taking images of the brain / spine. The results will be compared to the results of MRI taken without Dotarem.

Detailed Description
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This is a study involving the use of Magnetic Resonance Imaging (MRI) contrast agents called Dotarem®. The purpose of this study is to look at the safety (what are the side effects) and efficacy (how well does it work) of Dotarem® when used for taking images of the brain and spine. The results of the MRI will be compared to the results of images taken without Dotarem®.

Official Title
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Safety and Efficacy Evaluation of DOTAREM® in Magnetic Resonance Imaging (MRI) in Patients With Central Nervous System (CNS) Lesions.

Conditions
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Diagnostic Self Evaluation, Central Nervous System Diseases

Intervention / Treatment
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* Drug: Dotarem (gadoterate meglumine)
* Drug: Magnevist (gadopentetate dimeglumine)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult subject and pediatric subjects (aged greater than or equal to two (2) years). Is referred for a contrast-enhanced MRI of the CNS based on the results of a previous imaging procedure. Female of childbearing potential patients must have effective contraception (contraceptive pill or intra-uterine device) or be surgically sterilized or post-menopausal (minimum 12 months amenorrhea), or have a documented negative urine pregnancy test within 24 hours prior to study MRI. Has been fully informed about the study, and has consented to participate. Exclusion Criteria: Having acute or chronic grade IV or V renal insufficiency. Known class III/IV congestive heart failure. Suffering from long QT syndrome. Unstable health condition or circumstances (e.g. suffering from severe claustrophobia). Having any contraindications to MRI such as a pace-maker, magnetic material or any other conditions that would preclude proximity to a strong magnetic field. Known allergy to Gadolinium chelates. Having received any contrast agent within 3 days prior to study contrast administration, or is scheduled to receive any contrast agent within 24 hours after the study contrast administration. Pregnant, breast feeding, or planning to become pregnant during the trial. Previously participated in this trial. Having participated within 30 days in another clinical trial involving an investigational drug. Any condition which, based on the investigator's clinical judgement, would prevent the patient from completing all trial assessments and visits. Inability or unwillingness to cooperate with the requirements of this trial.

Ages Eligible for Study
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Minimum Age: 2 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dotarem (gadoterate meglumine )<br>Dotarem and Magnevist were randomised as 2:1 ratio for adult patients. | Drug: Dotarem (gadoterate meglumine)<br>* 0.1 mmol/kg by body weight, single IV injection<br>* Other names: Dotarem;|
| Active Comparator: Magnevist (gadopentetate dimeglumine)<br>Dotarem and Magnevist were randomised as 2:1 ratio | Drug: Magnevist (gadopentetate dimeglumine)<br>* 0.1 mmol/kg by body weight, single IV injection<br>* Other names: Magnevist;|
| Experimental: Dotarem 2 (gadoterate meglumine )<br>Pediatric patients were assigned to Dotarem group only. | Drug: Dotarem (gadoterate meglumine)<br>* 0.1 mmol/kg by body weight, single IV injection<br>* Other names: Dotarem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both Pre and Paired Evaluation | To demonstrate the superiority of combined unenhanced and Dotarem enhanced MRI (PAIRED) compared to unenhanced MRI (PRE) in terms of lesion visualization. Unenhanced MRI refers to MRI before administration of contrast agent. Enhanced MRI refers to MRI after contrast agent injection. Pre refers to unenhanced MRI. PAIRED refer to combined unenhanced and enhanced MRI. The measure used a specific scale with 3-point levels to assess lesion visualization. At lesion level, the scale range is from 0 through 1 to 2. Score 0 means a worse outcome and score 2 means a better outcome. Patient score is the sum of all lesion scores. Up to 5 of the largest representative lesions were assessed. At patient level, the maximum score is 10, minimum score is 0. | up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Image Quality Score | Image quality was evaluated for each lesion according to a 3-point scale with the following grades; poor (1), fair (2) or good (3), and an overall score per patient was calculated. At patient level, the maximum score is 3, minimum score is 1. Higher scores mean a better image quality. | up to 24 hours | 
| Diagnostic Confidence Score | Level of diagnostic confidence when evaluating the MRI modalities was graded using a 5-point scale as nil (1), poor (2), moderate (3), high (4) and excellent (5). | up to 24 hours | 
| Number of Lesions | The number of lesions for which observations could be made was calculated for each MRI modality and results are summarized per patient | up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CNS, Contrast Agent, MRI, Dotarem, Magnevist