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

Phase 4

Completed

Conditions: Brain Disease

Interventions: Drug: gadoteridol
Drug: gadobutrol

Registration Number: NCT01613417

Lead Sponsor: Bracco Diagnostics, Inc

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 229

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
MRI with Gadobutrol	gadobutrol	MRI after 0.1 mmol/kg IV Gadovist/Gadavist, then with 0.1 mmol/kg ProHance. MRI performed after both agents with identical sequences.
MRI with Gadoteridol	gadoteridol	MRI after 0.1 mmol/kg IV ProHance, then with 0.1 mmol/kg Gadovist/Gadavist. MRI performed after both agents with identical sequences.
MRI with Gadoteridol	gadobutrol	MRI after 0.1 mmol/kg IV ProHance, then with 0.1 mmol/kg Gadovist/Gadavist. MRI performed after both agents with identical sequences.
MRI with Gadobutrol	gadoteridol	MRI after 0.1 mmol/kg IV Gadovist/Gadavist, then with 0.1 mmol/kg ProHance. MRI performed after both agents with identical sequences.

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 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.

Secondary Outcome Measures

Name	Time	Method
Lesion Detection	5-10 minutes Postdose	Lesion detection rate by contrast agent and reader
Extent of Disease	Comparison of image sets obtained within 2 to 14 days	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.
Percentage Signal Intensity Enhancement on Postdose Images	5-10 minutes Postdose	Mean difference in percentage signal intensity enhancement on postdose T1-weighted SE/FSE images (ProHance - Gadovist/Gadavist)
Lesion Border Delineation	Comparison of image sets obtained within 2 to 14 days	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.
Lesion Contrast Enhancement	Comparison of image sets obtained within 2 to 14 days	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.
Lesion to Background Ratio on Post T1-weighed Spin Echo Images	5-10 minutes Postdose	Mean of difference in signal intensity postdose (ProHance - Gadovist/Gadavist)
Lesion Internal Morphology	Comparison of image sets obtained within 2 to 14 days	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.
Accuracy for Tumor Characterization	5-10 minutes Postdose	Blinded reader assessment of accuracy of tumor characterization (benign/malignant) - patient level assessment