Crossover Comparison of MultiHance and Dotarem

Phase 4

Completed

Conditions: Brain Disease

Interventions: Drug: MultiHance 0.1 mmol/kg
Drug: MultiHance 0.05 mmol/kg
Drug: Dotarem

Registration Number: NCT02070380

Lead Sponsor: Bracco Diagnostics, Inc

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 179

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MultiHance 0.1 then Dotarem 0.1 mmol/kg	MultiHance 0.1 mmol/kg	MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg
MultiHance 0.05 then Dotarem 0.1 mmol/kg	MultiHance 0.05 mmol/kg	MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg
Dotarem 0.1 then MultiHance 0.1 mmol/kg	MultiHance 0.1 mmol/kg	Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg
Dotarem 0.1 then MultiHance 0.05 mmol/kg	MultiHance 0.05 mmol/kg	Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg
MultiHance 0.1 then Dotarem 0.1 mmol/kg	Dotarem	MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg
MultiHance 0.05 then Dotarem 0.1 mmol/kg	Dotarem	MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg
Dotarem 0.1 then MultiHance 0.1 mmol/kg	Dotarem	Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg
Dotarem 0.1 then MultiHance 0.05 mmol/kg	Dotarem	Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg

Primary Outcome Measures

Name	Time	Method
Global Diagnostic Preference Between the Two Exams	Comparison of image sets obtained within 2 to 14 days	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.

Secondary Outcome Measures

Name	Time	Method
Lesion Border Delineation	Comparison of image sets obtained within 2 to 14 days	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.
Lesion Internal Morphology	Comparison of image sets obtained within 2 to 14 days	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.
Extent of Disease	Comparison of image sets obtained within 2 to 14 days	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.
Lesion Contrast Enhancement	Comparison of image sets obtained within 2 to 14 days	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.
Lesion to Background Ratio on Post T1-weighed Spin Echo Images	5-10 minutes Postdose	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)"
Lesion-brain Contrast-to-noise Ratio	5-10 minutes Postdose	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)"