Crossover Comparison of MultiHance and Dotarem

Study Overview
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Brief Summary
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This study aims at a comparison between MultiHance at a dose of 0.1 mmol/kg and 0.05 mmol/kg and Dotarem at a dose of 0.1 mmol/kg in brain tumor patients to show superiority of MultiHance.

Detailed Description
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This crossover study aims at a comparison between 0.1 mmol/kg MultiHance and 0.1 mmol/kg Dotarem, between 0.05 MultiHance and 0.1 mmol/kg Dotarem in terms of diagnostic preference at CE-MRI in brain tumor patients to show superiority of MultiHance.

Official Title
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Phase IV, Double Blind, Multi-Center, Randomized, Two-Arm Crossover Study to Compare 0.1 mmol/kg of MultiHance With 0.1 mmol/kg of Dotarem and 0.05 mmol/kg of MultiHance With 0.1 mmol/kg of Dotarem in MRI of the Brain

Conditions
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Brain Disease

Intervention / Treatment
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* Drug: MultiHance 0.1 mmol/kg
* Drug: Dotarem
* Drug: MultiHance 0.05 mmol/kg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are at least 18 years of age or older Are able to give written informed consent and are willing to comply with the protocol requirements Are scheduled to undergo MRI Are willing to undergo two MRI procedures within 14 days Have confirmed or are highly suspected to have brain tumor(s) (primary or secondary), as determined by: Clinical/neurological symptomatology; Diagnostic testing, such as CT or previous MRI examinations; or Have had recent brain surgery and are to be evaluated for recurrence Exclusion Criteria: Are pregnant or lactating females. Exclude the possibility of pregnancy: By testing on site at the institution within 24 hours prior to the start of each investigational product administration; or By history (i.e., tubal ligation or hysterectomy); or Post menopausal with a minimum of 1 year without menses Have any known allergy to one or more of the ingredients in the investigational products, or have a history of hypersensitivity to any metals Have congestive heart failure (class IV according to the classification of the New York Heart Association) Have suffered a stroke within a year Have received or are scheduled to receive any other contrast medium in the 24 hours preceding through the 24 hours following Exam 1, and in the 24 hours preceding through the 24 hours following Exam 2 Have received or are scheduled to receive an investigational compound and/or medical device within 30 days before admission into the present study, through the 24 hours post-administration of the second investigational product Have moderate-to-severe renal impairment, defined as Glomerular Filtration Rate (GFR)/estimated GFR < 45 mL/min Have been previously entered into this study Have received or are scheduled for one of the following: Surgical or chemotherapeutic treatment within three weeks prior to the first examination or between the two examinations Initiation of steroid therapy between the two examinations Radiosurgery between the two examinations Have any contraindications to MRI such as a pace-maker, magnetic material (i.e., surgical clips) or any other conditions that would preclude proximity to a strong magnetic field Are suffering from severe claustrophobia Have any medical condition or other circumstances which would significantly decrease the chances of obtaining reliable data, achieving study objectives, or completing the study and/or post-dose follow-up examinations

Ages Eligible for Study
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Minimum Age: 18 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MultiHance 0.1 then Dotarem 0.1 mmol/kg<br>MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg | Drug: MultiHance 0.1 mmol/kg<br>* MultiHance administered at 0.1 mmol/kg<br>Drug: Dotarem<br>* Dotarem administered at 0.1 mmol/kg<br>* Other names: Dotarem 0.1 mmol/kg;|
| Experimental: MultiHance 0.05 then Dotarem 0.1 mmol/kg<br>MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg | Drug: Dotarem<br>* Dotarem administered at 0.1 mmol/kg<br>* Other names: Dotarem 0.1 mmol/kg;Drug: MultiHance 0.05 mmol/kg<br>* MultiHance administered at 0.05 mmol/kg<br>|
| Active Comparator: Dotarem 0.1 then MultiHance 0.1 mmol/kg<br>Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg | Drug: MultiHance 0.1 mmol/kg<br>* MultiHance administered at 0.1 mmol/kg<br>Drug: Dotarem<br>* Dotarem administered at 0.1 mmol/kg<br>* Other names: Dotarem 0.1 mmol/kg;|
| Active Comparator: Dotarem 0.1 then MultiHance 0.05 mmol/kg<br>Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg | Drug: Dotarem<br>* Dotarem administered at 0.1 mmol/kg<br>* Other names: Dotarem 0.1 mmol/kg;Drug: MultiHance 0.05 mmol/kg<br>* MultiHance administered at 0.05 mmol/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Diagnostic Preference Between the Two Exams | Assessed by 3 blinded readers for each of the 159 patients who had post-dose exams for both MultiHance, 0.1 mmol/kg and 0.05 mmol/kg doses, and Dotarem 0.1 mmol/kg. Readers assessed whether images with MultiHance were preferred or images with Dotarem were preferred, or whether images after both exams were considered equal. An image set deemed technically inadequate by a blinded reader was excluded from efficacy analysis for that specific reader. Therefore, the number of participant exams evaluated by each reader differed slightly across readers and endpoints. | Comparison of image sets obtained within 2 to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lesion Border Delineation | Assessed by 3 blinded readers for each of the 159 patients who had post-dose exams for both MultiHance, 0.1 mmol/kg and 0.05 mmol/kg doses, and Dotarem 0.1 mmol/kg. Readers assessed whether images with MultiHance were preferred or images with Dotarem were preferred, or whether images after both exams were considered equal. An image set deemed technically inadequate by a blinded reader was excluded from efficacy analysis for that specific reader. Therefore, the number of participant exams evaluated by each reader differed slightly across readers and endpoints. | Comparison of image sets obtained within 2 to 14 days | 
| Lesion Internal Morphology | Assessed by 3 blinded readers for each of the 159 patients who had post-dose exams for both MultiHance, 0.1 mmol/kg and 0.05 mmol/kg doses, and Dotarem 0.1 mmol/kg. Readers assessed whether images with MultiHance were preferred or images with Dotarem were preferred, or whether images after both exams were considered equal. An image set deemed technically inadequate by a blinded reader was excluded from efficacy analysis for that specific reader. Therefore, the number of participant exams evaluated by each reader differed slightly across readers and endpoints. | Comparison of image sets obtained within 2 to 14 days | 
| Extent of Disease | Assessed by 3 blinded readers for each of the 159 patients who had post-dose exams for both MultiHance, 0.1 mmol/kg and 0.05 mmol/kg doses, and Dotarem 0.1 mmol/kg. Readers assessed whether images with MultiHance were preferred or images with Dotarem were preferred, or whether images after both exams were considered equal. An image set deemed technically inadequate by a blinded reader was excluded from efficacy analysis for that specific reader. Therefore, the number of participant exams evaluated by each reader differed slightly across readers and endpoints. | Comparison of image sets obtained within 2 to 14 days | 
| Lesion Contrast Enhancement | Assessed by 3 blinded readers for each of the 159 patients who had post-dose exams for both MultiHance, 0.1 mmol/kg and 0.05 mmol/kg doses, and Dotarem 0.1 mmol/kg. Readers assessed whether images with MultiHance were preferred or images with Dotarem were preferred, or whether images after both exams were considered equal. An image set deemed technically inadequate by a blinded reader was excluded from efficacy analysis for that specific reader. Therefore, the number of participant exams evaluated by each reader differed slightly across readers and endpoints. | Comparison of image sets obtained within 2 to 14 days | 
| Lesion to Background Ratio on Post T1-weighed Spin Echo Images | The Unit of Measure is lesion-to-background ratio based on lesions assessed. For each lesion, Lesion-to-background ratio (LBR) = SI of lesion/SI of brain. Firstly, LBR of each lesion was assessed for each contrast agent postdose image separately, then the difference in LBR between MultiHance and Dotarem was calculated. The number presented in the result table below is the mean difference in LBR postdose (MultiHance - Dotarem) | 5-10 minutes Postdose | 
| Lesion-brain Contrast-to-noise Ratio | The Unit of Measure is contrast-to-noise ratio based on lesions assessed. For each lesion, Lesion-brain Contrast-to-noise Ratio (CNR) = [(SI of lesion - SI of brain)/SD for SI of noise] on Postdose Images of each lesion was calculated for each contrast agent image separately, then the difference in CNR between MultiHance and Dotarem was calculated. The number presented in the result table below is the mean difference in CNR (MultiHance - Dotarem) | 5-10 minutes Postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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confirmed brain disease, highly suspected brain disease