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Crossover Comparison of MultiHance and Dotarem (BENEFIT)

Primary Purpose

Brain Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
MultiHance 0.1 mmol/kg
Dotarem
MultiHance 0.05 mmol/kg
Sponsored by
Bracco Diagnostics, Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Brain Disease focused on measuring confirmed brain disease, highly suspected brain disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Samaritan Health Services

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

MultiHance 0.1 then Dotarem 0.1 mmol/kg

MultiHance 0.05 then Dotarem 0.1 mmol/kg

Dotarem 0.1 then MultiHance 0.1 mmol/kg

Dotarem 0.1 then MultiHance 0.05 mmol/kg

Arm Description

MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg

MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg

Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg

Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg

Outcomes

Primary Outcome Measures

Global Diagnostic Preference Between the Two Exams
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

Lesion Border Delineation
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
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
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
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
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
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)"

Full Information

First Posted
February 20, 2014
Last Updated
November 14, 2016
Sponsor
Bracco Diagnostics, Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02070380
Brief Title
Crossover Comparison of MultiHance and Dotarem
Acronym
BENEFIT
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 Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
March 2015 (Actual)
Study Completion Date
March 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bracco Diagnostics, Inc

4. Oversight

Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Disease
Keywords
confirmed brain disease, highly suspected brain disease

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
179 (Actual)

8. Arms, Groups, and Interventions

Arm Title
MultiHance 0.1 then Dotarem 0.1 mmol/kg
Arm Type
Experimental
Arm Description
MultiHance 0.1 mmol/kg Then Dotarem 0.1 mmol/kg
Arm Title
MultiHance 0.05 then Dotarem 0.1 mmol/kg
Arm Type
Experimental
Arm Description
MultiHance 0.05 mmol/kg Then Dotarem 0.1 mmol/kg
Arm Title
Dotarem 0.1 then MultiHance 0.1 mmol/kg
Arm Type
Active Comparator
Arm Description
Dotarem 0.1 mmol/kg Then MultiHance 0.1 mmol/kg
Arm Title
Dotarem 0.1 then MultiHance 0.05 mmol/kg
Arm Type
Active Comparator
Arm Description
Dotarem 0.1 mmol/kg Then MultiHance 0.05 mmol/kg
Intervention Type
Drug
Intervention Name(s)
MultiHance 0.1 mmol/kg
Intervention Description
MultiHance administered at 0.1 mmol/kg
Intervention Type
Drug
Intervention Name(s)
Dotarem
Other Intervention Name(s)
Dotarem 0.1 mmol/kg
Intervention Description
Dotarem administered at 0.1 mmol/kg
Intervention Type
Drug
Intervention Name(s)
MultiHance 0.05 mmol/kg
Intervention Description
MultiHance administered at 0.05 mmol/kg
Primary Outcome Measure Information:
Title
Global Diagnostic Preference Between the Two Exams
Description
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.
Time Frame
Comparison of image sets obtained within 2 to 14 days
Secondary Outcome Measure Information:
Title
Lesion Border Delineation
Description
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.
Time Frame
Comparison of image sets obtained within 2 to 14 days
Title
Lesion Internal Morphology
Description
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.
Time Frame
Comparison of image sets obtained within 2 to 14 days
Title
Extent of Disease
Description
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.
Time Frame
Comparison of image sets obtained within 2 to 14 days
Title
Lesion Contrast Enhancement
Description
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.
Time Frame
Comparison of image sets obtained within 2 to 14 days
Title
Lesion to Background Ratio on Post T1-weighed Spin Echo Images
Description
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)"
Time Frame
5-10 minutes Postdose
Title
Lesion-brain Contrast-to-noise Ratio
Description
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)"
Time Frame
5-10 minutes Postdose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gianpaolo Pirovano, MD
Organizational Affiliation
Bracco Diagnostics, Inc
Official's Role
Study Director
Facility Information:
Facility Name
Samaritan Health Services
City
Corvallis
State/Province
Oregon
ZIP/Postal Code
97330
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Crossover Comparison of MultiHance and Dotarem

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