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

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)

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.

Study Overview

• Status: Completed
• Conditions: Brain Disease
• Intervention / Treatment: Drug: gadoteridol; Drug: gadobutrol

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.

• Study Type: Interventional
• Enrollment (Actual): 229
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MRI with 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.	Drug: gadoteridol; ProHance 0.1 mmol/kg; Other Names: ProHance; Drug: gadobutrol; Gadovist/Gadavist 0.1 mmol/kg; Other Names: Gadovist, Gadavist
Active Comparator: MRI with 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.	Drug: gadoteridol; ProHance 0.1 mmol/kg; Other Names: ProHance; Drug: gadobutrol; Gadovist/Gadavist 0.1 mmol/kg; Other Names: Gadovist, Gadavist

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bracco Diagnostics, Inc

Publications and helpful links

General Publications

• Maravilla KR, Smith MP, Vymazal J, Goyal M, Herman M, Baima JJ, Babbel R, Vaneckova M, Zizka J, Colosimo C, Urbanczyk-Zawadzka M, Mechl M, Bag AK, Bastianello S, Bueltmann E, Hirai T, Frattini T, Kirchin MA, Pirovano G. Are there differences between macrocyclic gadolinium contrast agents for brain tumor imaging? Results of a multicenter intraindividual crossover comparison of gadobutrol with gadoteridol (the TRUTH study). AJNR Am J Neuroradiol. 2015 Jan;36(1):14-23. doi: 10.3174/ajnr.A4154. Epub 2014 Oct 9.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: June 4, 2012
• First Submitted That Met QC Criteria: June 5, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Estimate): July 1, 2015
• Last Update Submitted That Met QC Criteria: June 4, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Have confirmed or are highly suspected of brain disease
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Brain Diseases
• Other Study ID Numbers: PH-107