Comparison of Prohance® With Gadovist®/Gadavist™ in Magnetic Resonance Imaging (MRI) of the Brain

Study Overview
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Brief Summary
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This study aims at a direct comparison between ProHance (0.1 mmol/kg) and a validated comparator Gadovist/Gadavist (0.1 mmol/kg) in a crossover intra-individual design in subjects with brain tumors to confirm the identical overall technical and diagnostic performance of the two MR contrast agents.

Detailed Description
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Adult patients were given two MRI exams, one after injection of ProHance (0.1 mmol/kg) and one after injection of Gadovist/Gadavist (0.1 mmol/kg). The exams were performed with identical equipment and imaging parameters with the order of the two exams randomized and 2-14 days between the first and the second MRI exam. Image data was evaluated by 3 expert neuroradiologist blinded to the agent administered and patient clinical data.

Official Title
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Phase IV, Double-blind, Multi-center, Randomized, Crossover Study to Compare 0.1 mmol/kg of Prohance® With 0.1 mmol/kg of Gadovist®/Gadavist™ in Magnetic Resonance Imaging (MRI) of the Brain (TRUTH)

Conditions
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Brain Disease

Intervention / Treatment
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* Drug: gadoteridol
* Drug: gadobutrol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are scheduled to undergo MRI Are willing to undergo two MRI procedures within 14 days Have confirmed or are highly suspected of brain disease likely to enhance as determined by the following: Clinical/neurological symptomatology; Diagnostic testing, such as CT or previous MRI examinations; or Have had previous 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; see Appendix A) 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 a GFR/eGFR < 45 mL/min. Have been previously entered into this study Have received or are scheduled for one of the following: Surgery 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

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 |
| --- | --- |
| Active Comparator: MRI with Gadoteridol<br>MRI after 0.1 mmol/kg IV ProHance, then with 0.1 mmol/kg Gadovist/Gadavist. MRI performed after both agents with identical sequences. | Drug: gadoteridol<br>* ProHance 0.1 mmol/kg<br>* Other names: ProHance;Drug: gadobutrol<br>* Gadovist/Gadavist 0.1 mmol/kg<br>* Other names: Gadovist, Gadavist;|
| Active Comparator: MRI with Gadobutrol<br>MRI after 0.1 mmol/kg IV Gadovist/Gadavist, then with 0.1 mmol/kg ProHance. MRI performed after both agents with identical sequences. | Drug: gadoteridol<br>* ProHance 0.1 mmol/kg<br>* Other names: ProHance;Drug: gadobutrol<br>* Gadovist/Gadavist 0.1 mmol/kg<br>* Other names: Gadovist, Gadavist;|

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 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | 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 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days | 
| Lesion Internal Morphology | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days | 
| Extent of Disease | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days | 
| Lesion Contrast Enhancement | Assessed by 3 blinded readers for each of the 198 patients who had post-dose exams for both ProHance and Gadovist/Gadavist. Readers assessed whether images with ProHance were preferred or images with Gadovist/Gadavist were preferred, or whether images after both exams were considered equal. | Comparison of image sets obtained within 2 to 14 days | 
| Lesion to Background Ratio on Post T1-weighed Spin Echo Images | Mean of difference in signal intensity postdose (ProHance - Gadovist/Gadavist) | 5-10 minutes Postdose | 
| Percentage Signal Intensity Enhancement on Postdose Images | Mean difference in percentage signal intensity enhancement on postdose T1-weighted SE/FSE images (ProHance - Gadovist/Gadavist) | 5-10 minutes Postdose | 
| Lesion Detection | Lesion detection rate by contrast agent and reader | 5-10 minutes Postdose | 
| Accuracy for Tumor Characterization | Blinded reader assessment of accuracy of tumor characterization (benign/malignant) - patient level assessment | 5-10 minutes Postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Have confirmed or are highly suspected of brain disease