Crossover Comparison of MultiHance and Dotarem (BENEFIT)

• ClinicalTrials.gov Identifier: NCT02070380
• Recruitment Status: Completed
• First Posted: February 25, 2014
• Results First Posted: January 10, 2017
• Last Update Posted: January 10, 2017
• Sponsor: Bracco Diagnostics, Inc
• Information provided by (Responsible Party): Bracco Diagnostics, Inc

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain Disease	Drug: MultiHance 0.1 mmol/kg; Drug: Dotarem; Drug: MultiHance 0.05 mmol/kg	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 179 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Phase IV, Double Blind, Multi-Center, Randomized, Two-Arm Crossover Study to Compare 0.1 mmol/kg of MultiHance With 0.1 mmol/kg of Dotarem and 0.05 mmol/kg of MultiHance With 0.1 mmol/kg of Dotarem in MRI of the Brain
• Study Start Date: February 2014
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: March 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: MultiHance 0.1 then Dotarem 0.1 mmol/kg; MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg	Drug: MultiHance 0.1 mmol/kg; MultiHance administered at 0.1 mmol/kg; Drug: Dotarem; Dotarem administered at 0.1 mmol/kg; Other Name: Dotarem 0.1 mmol/kg
Experimental: MultiHance 0.05 then Dotarem 0.1 mmol/kg; MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg	Drug: Dotarem; Dotarem administered at 0.1 mmol/kg; Other Name: Dotarem 0.1 mmol/kg; Drug: MultiHance 0.05 mmol/kg; MultiHance administered at 0.05 mmol/kg
Active Comparator: Dotarem 0.1 then MultiHance 0.1 mmol/kg; Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg	Drug: MultiHance 0.1 mmol/kg; MultiHance administered at 0.1 mmol/kg; Drug: Dotarem; Dotarem administered at 0.1 mmol/kg; Other Name: Dotarem 0.1 mmol/kg
Active Comparator: Dotarem 0.1 then MultiHance 0.05 mmol/kg; Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg	Drug: Dotarem; Dotarem administered at 0.1 mmol/kg; Other Name: Dotarem 0.1 mmol/kg; Drug: MultiHance 0.05 mmol/kg; MultiHance administered at 0.05 mmol/kg

Outcome Measures

Primary Outcome Measures :

1. 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 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 :

1. Lesion Border Delineation [ Time Frame: 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.
2. Lesion Internal Morphology [ Time Frame: 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.
3. Extent of Disease [ Time Frame: 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.
4. Lesion Contrast Enhancement [ Time Frame: 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.
5. Lesion to Background Ratio on Post T1-weighed Spin Echo Images [ Time Frame: 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)"
6. Lesion-brain Contrast-to-noise Ratio [ Time Frame: 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)"

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Oregon

Samaritan Health Services

Corvallis, Oregon, United States, 97330

Sponsors and Collaborators

Bracco Diagnostics, Inc

Investigators

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

More Information

• Responsible Party: Bracco Diagnostics, Inc
• ClinicalTrials.gov Identifier: NCT02070380
• Other Study ID Numbers: MH-148
• First Posted: February 25, 2014
• Results First Posted: January 10, 2017
• Last Update Posted: January 10, 2017
• Last Verified: November 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Bracco Diagnostics, Inc:

confirmed brain disease; highly suspected brain disease

Additional relevant MeSH terms:

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases