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

• ClinicalTrials.gov Identifier: NCT01613417
• Recruitment Status: Completed
• First Posted: June 7, 2012
• Results First Posted: June 3, 2015
• Last Update Posted: July 1, 2015
• Sponsor: Bracco Diagnostics, Inc
• Information provided by (Responsible Party): Bracco Diagnostics, Inc

Tracking Information

• First Submitted Date: June 4, 2012
• First Posted Date: June 7, 2012
• Results First Submitted Date: April 28, 2015
• Results First Posted Date: June 3, 2015
• Last Update Posted Date: July 1, 2015
• Study Start Date: August 2012
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 15, 2015)

Global Diagnostic Preference Between the Two Exams [ Time Frame: 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.

Original Primary Outcome Measures (submitted: June 5, 2012)

Non-inferiority of each exam based on pre-dose and post dose images [ Time Frame: Up to 14 days ]

To show non-inferiority of a 0.1 mmol/kg dose of PROHANCE as compared to 0.1 mmol/kg dose of GADOVIST/GADAVIST, in terms of the by-subject global diagnostic preference between exams (i.e., based on predose + postdose image sets).

Current Secondary Outcome Measures (submitted: May 15, 2015)

• Lesion Border Delineation [ Time Frame: 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 Internal Morphology [ Time Frame: 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.
• Extent of Disease [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 5-10 minutes Postdose ]
  Mean of difference in signal intensity postdose (ProHance - Gadovist/Gadavist)
• Percentage Signal Intensity Enhancement on Postdose Images [ Time Frame: 5-10 minutes Postdose ]
  Mean difference in percentage signal intensity enhancement on postdose T1-weighted SE/FSE images (ProHance - Gadovist/Gadavist)
• Lesion Detection [ Time Frame: 5-10 minutes Postdose ]
  Lesion detection rate by contrast agent and reader
• Accuracy for Tumor Characterization [ Time Frame: 5-10 minutes Postdose ]
  Blinded reader assessment of accuracy of tumor characterization (benign/malignant) - patient level assessment

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Prohance® With Gadovist®/Gadavist™ in Magnetic Resonance Imaging (MRI) of the Brain
• Official Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Diagnostic
• Condition: Brain Disease

Intervention

• Drug: gadoteridol
  ProHance 0.1 mmol/kg
  Other Name: ProHance
• Drug: gadobutrol
  Gadovist/Gadavist 0.1 mmol/kg
  Other Name: Gadovist, Gadavist

Study Arms

• 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.
  Interventions:

  • Drug: gadoteridol
  • Drug: gadobutrol
• 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.
  Interventions:

  • Drug: gadoteridol
  • Drug: gadobutrol

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 8, 2014): 229
• Original Estimated Enrollment (submitted: June 5, 2012): 206
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01613417
• Other Study ID Numbers: PH-107
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Bracco Diagnostics, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Bracco Diagnostics, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gianpaolo Pirovano, MD; Bracco Diagnostics, Inc

• PRS Account: Bracco Diagnostics, Inc
• Verification Date: June 2015