Trial Outcomes & Findings for Multihance at 3 Tesla (3T) in Brain Tumors (NCT NCT00395863)

NCT ID: NCT00395863

Last Updated: 2020-11-05

Results Overview

Assessed by 3 blinded Readers for each of the 41 patients who had both MultiHance and Magnevist post dose MRI exam to assess whether the image with MultiHance was preferred, both contrast agents were equal, or the image with Magnevist was preferred. Each patient's image was reviewed by 3 readers.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 46 participants
• Primary outcome timeframe: Postdose Images for MultiHance Exam and for Magnevist Exam Compared
• Results posted on: 2020-11-05

Participant Flow

A total of 47 patients were recruited from March 2007 through February 2008 at 8 clinical trial sites. from Feb/18/2008 to Feb/22/2008, an off-site assessment of the images was performed by 3 board-certified radiologists who were blinded to which contrast agent was used, any patient's clinical information & any results from other imaging studies.

47 patients enrolled (signed informed consent); 46 were randomized and dosed.

Participant milestones

Measure	MultiHance, Then Magnevist 0.1 mmol/kg injection of each product	Magnevist, Then MultiHance 0.1 mmol/kg injection of each product
Overall Study STARTED	23	23
Overall Study COMPLETED	21	20
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Measure	MultiHance, Then Magnevist 0.1 mmol/kg injection of each product	Magnevist, Then MultiHance 0.1 mmol/kg injection of each product
Overall Study Patients did not complete both exams	2	3

Baseline Characteristics

Multihance at 3 Tesla (3T) in Brain Tumors

Baseline characteristics by cohort

Measure	MultiHance, Then Magnevist n=23 Participants 0.1 mmol/kg injection of each product	Magnevist, Then MultiHance n=23 Participants 0.1 mmol/kg injection of each product	Total n=46 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=93 Participants	20 Participants n=4 Participants	39 Participants n=27 Participants
Age, Categorical >=65 years	4 Participants n=93 Participants	3 Participants n=4 Participants	7 Participants n=27 Participants
Age, Continuous	50.79 years STANDARD_DEVIATION 15.497 • n=93 Participants	48.08 years STANDARD_DEVIATION 16.064 • n=4 Participants	49.43 years STANDARD_DEVIATION 15.667 • n=27 Participants
Sex: Female, Male Female	12 Participants n=93 Participants	9 Participants n=4 Participants	21 Participants n=27 Participants
Sex: Female, Male Male	11 Participants n=93 Participants	14 Participants n=4 Participants	25 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	3 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	23 Participants n=93 Participants	19 Participants n=4 Participants	42 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	23 participants n=93 Participants	23 participants n=4 Participants	46 participants n=27 Participants

PRIMARY outcome

Timeframe: Postdose Images for MultiHance Exam and for Magnevist Exam Compared

Population: Include all intention-to-treat (ITT) population. The number of units analyzed is the total number of technically adequate postdose images assessed by the reader from the total number of participants with both MultiHance- and Magnevist-enhanced images. Patient-level analysis.

Assessed by 3 blinded Readers for each of the 41 patients who had both MultiHance and Magnevist post dose MRI exam to assess whether the image with MultiHance was preferred, both contrast agents were equal, or the image with Magnevist was preferred. Each patient's image was reviewed by 3 readers.

Outcome measures

Measure	Reader 1 n=41 Participants Reader 1 Assessment	Reader 2 n=41 Participants Reader 2 Assessment	Reader 3 n=41 Participants Reader 3 Assessment
Global Diagnostic Preference Between the Two Exams Magnevist Preferred	0 Contrast-enhanced Images	1 Contrast-enhanced Images	0 Contrast-enhanced Images
Global Diagnostic Preference Between the Two Exams MultiHance Preferred	22 Contrast-enhanced Images	21 Contrast-enhanced Images	27 Contrast-enhanced Images
Global Diagnostic Preference Between the Two Exams Contrast Agents Equal	19 Contrast-enhanced Images	19 Contrast-enhanced Images	14 Contrast-enhanced Images

SECONDARY outcome

Timeframe: Postdose Images for MultiHance Exam and for Magnevist Exam Compared

Population: Include all ITT population. The number of units analyzed is the total number of technically adequate postdose images assessed by the reader from the total number of participants with both MultiHance- and Magnevist-enhanced images. Patient-level analysis.

Assessed by 3 blinded Readers for each of the 41 patients who had both MultiHance and Magnevist post dose MRI exam to assess whether the image with MultiHance was preferred, both contrast agents were equal, or the image with Magnevist was preferred.

Outcome measures

Measure	Reader 1 n=41 Contrast-enhanced Images Reader 1 Assessment	Reader 2 n=41 Contrast-enhanced Images Reader 2 Assessment	Reader 3 n=41 Contrast-enhanced Images Reader 3 Assessment
Lesion Border Delineation MultiHance Preferred	14 Contrast-enhanced Images	11 Contrast-enhanced Images	13 Contrast-enhanced Images
Lesion Border Delineation Contrast Agents Equal	27 Contrast-enhanced Images	30 Contrast-enhanced Images	28 Contrast-enhanced Images
Lesion Border Delineation Magnevist Preferred	0 Contrast-enhanced Images	0 Contrast-enhanced Images	0 Contrast-enhanced Images

SECONDARY outcome

Timeframe: Postdose Images for MultiHance Exam and for Magnevist Exam Compared

Population: Include all ITT population. The number of units analyzed is the total number of technically adequate postdose images assessed by the reader from the total number of participants with both MultiHance- and Magnevist-enhanced images. Patient-level analysis.

Assessed by 3 blinded Readers for each of the 41 patients who had both MultiHance and Magnevist post dose MRI exam to assess whether the image with MultiHance was preferred, both contrast agents were equal, or the image with Magnevist was preferred.

Outcome measures

Measure	Reader 1 n=41 Contrast-enhanced Images Reader 1 Assessment	Reader 2 n=41 Contrast-enhanced Images Reader 2 Assessment	Reader 3 n=41 Contrast-enhanced Images Reader 3 Assessment
Lesion Contrast Enhancement Between the Two Exams MultiHance Preferred	22 Contrast-enhanced Images	20 Contrast-enhanced Images	22 Contrast-enhanced Images
Lesion Contrast Enhancement Between the Two Exams Contrast Agents Equal	19 Contrast-enhanced Images	20 Contrast-enhanced Images	18 Contrast-enhanced Images
Lesion Contrast Enhancement Between the Two Exams Magnevist Preferred	0 Contrast-enhanced Images	1 Contrast-enhanced Images	1 Contrast-enhanced Images

SECONDARY outcome

Timeframe: Predose and immediately postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Change from predose to postdose in lesion-to-brain ratio computed. Comparison of the differences in change were analyzed.

Outcome measures

Measure	Reader 1 n=27 Lesions Reader 1 Assessment	Reader 2 n=27 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 1 Predose	0.82 [ratio] Standard Deviation 0.17	0.85 [ratio] Standard Deviation 0.19	—
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 1 Postdose	1.50 [ratio] Standard Deviation 0.30	1.31 [ratio] Standard Deviation 0.21	—
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 1 Change from Baseline	0.68 [ratio] Standard Deviation 0.33	0.46 [ratio] Standard Deviation 0.24	—

SECONDARY outcome

Timeframe: Predose and immediately postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Change from predose to postdose in lesion-to-brain ratio computed. Comparison of the differences in change were analyzed.

Outcome measures

Measure	Reader 1 n=25 Lesions Reader 1 Assessment	Reader 2 n=25 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 2 Predose	0.82 [ratio] Standard Deviation 0.18	0.87 [ratio] Standard Deviation 0.17	—
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 2 Postdose	1.61 [ratio] Standard Deviation 0.28	1.36 [ratio] Standard Deviation 0.22	—
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 2 Change from Baseline	0.79 [ratio] Standard Deviation 0.36	0.49 [ratio] Standard Deviation 0.27	—

SECONDARY outcome

Timeframe: Predose and immediately postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Change from predose to postdose in lesion-to-brain ratio computed. Comparison of the differences in change were analyzed.

Outcome measures

Measure	Reader 1 n=26 Lesions Reader 1 Assessment	Reader 2 n=26 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 3 Predose	0.86 [ratio] Standard Deviation 0.17	0.91 [ratio] Standard Deviation 0.17	—
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 3 Postdose	1.67 [ratio] Standard Deviation 0.36	1.46 [ratio] Standard Deviation 0.26	—
Lesion-to-brain Ratio (LBR) for Each Lesion - Reader 3 Change from Baseline	0.81 [ratio] Standard Deviation 0.41	0.55 [ratio] Standard Deviation 0.31	—

SECONDARY outcome

Timeframe: Predose and immediately postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Change from predose to postdose in contrast-to-noise ratio computed. Comparison of the differences in change were analyzed.

Outcome measures

Measure	Reader 1 n=27 Lesions Reader 1 Assessment	Reader 2 n=27 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 1 Predose	-18.81 [ratio] Standard Deviation 19.22	-11.70 [ratio] Standard Deviation 20.85	—
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 1 Postdose	60.76 [ratio] Standard Deviation 66.88	26.87 [ratio] Standard Deviation 28.36	—
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 1 Change from Baseline	79.56 [ratio] Standard Deviation 71.57	38.57 [ratio] Standard Deviation 33.70	—

SECONDARY outcome

Timeframe: Predose and immediately postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Change from predose to postdose in contrast-to-noise ratio computed. Comparison of the differences in change were analyzed.

Outcome measures

Measure	Reader 1 n=25 Lesions Reader 1 Assessment	Reader 2 n=25 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 2 Predose	-18.30 [ratio] Standard Deviation 19.11	-14.38 [ratio] Standard Deviation 18.92	—
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 2 Postdose	65.96 [ratio] Standard Deviation 54.75	38.94 [ratio] Standard Deviation 40.41	—
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 2 Change from Baseline	84.26 [ratio] Standard Deviation 63.43	53.31 [ratio] Standard Deviation 52.46	—

SECONDARY outcome

Timeframe: Predose and immediately postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Change from predose to postdose in contrast-to-noise ratio computed. Comparison of the differences in change were analyzed.

Outcome measures

Measure	Reader 1 n=26 Lesions Reader 1 Assessment	Reader 2 n=26 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 3 Predose	-11.75 [ratio] Standard Deviation 17.70	-6.47 [ratio] Standard Deviation 17.20	—
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 3 Postdose	62.10 [ratio] Standard Deviation 42.92	42.34 [ratio] Standard Deviation 33.49	—
Contrast-to-noise Ratio (CNR) for Each Lesion - Reader 3 Change from Baseline	73.84 [ratio] Standard Deviation 47.60	48.81 [ratio] Standard Deviation 37.51	—

SECONDARY outcome

Timeframe: Postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Quantitative parameter derived from signal intensity (SI) measurements. LCE ([SI of lesion (postdose)-SI of lesion (predose)]/Standard SI of lesion (predose)]

Outcome measures

Measure	Reader 1 n=27 Lesions Reader 1 Assessment	Reader 2 n=27 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Percentage of Lesion Contrast Enhancement (LCE) - Reader 1	100.15 [percent] Standard Deviation 74.92	67.38 [percent] Standard Deviation 52.18	—

SECONDARY outcome

Timeframe: Postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Quantitative parameter derived from signal intensity (SI) measurements. LCE ([SI of lesion (postdose)-SI of lesion (predose)]/Standard SI of lesion (predose)]

Outcome measures

Measure	Reader 1 n=25 Lesions Reader 1 Assessment	Reader 2 n=25 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Percentage of Contrast Enhancement of the Lesion - Reader 2	106.42 [percent] Standard Deviation 84.97	72.81 [percent] Standard Deviation 65.70	—

SECONDARY outcome

Timeframe: Postdose

Population: Include all ITT population. The number of units analyzed are the total number of lesions assessed by the reader from the total number of participants. Lesion-level analysis.

Quantitative parameter derived from signal intensity (SI) measurements. LCE ([SI of lesion (postdose)-SI of lesion (predose)]/Standard SI of lesion (predose)]

Outcome measures

Measure	Reader 1 n=26 Lesions Reader 1 Assessment	Reader 2 n=26 Lesions Reader 2 Assessment	Reader 3 Reader 3 Assessment
Percentage of Contrast Enhancement of the Lesion - Reader 3	101.85 [percent] Standard Deviation 96.89	68.13 [percent] Standard Deviation 60.91	—

Adverse Events

MultiHance

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Magnevist

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	MultiHance n=43 participants at risk Adverse events experienced by patients occurred relative to the administration of MultiHance.	Magnevist n=44 participants at risk Adverse events experienced by patients occurred relative to the administration of Magnevist.
Ear and labyrinth disorders Ear discomfort	2.3% 1/43 • Number of events 1 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.	0.00% 0/44 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.
General disorders Fatigue	0.00% 0/43 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.	2.3% 1/44 • Number of events 1 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.
Nervous system disorders Headache	2.3% 1/43 • Number of events 1 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.	0.00% 0/44 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.
Gastrointestinal disorders Nausea	4.7% 2/43 • Number of events 2 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.	0.00% 0/44 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.
Gastrointestinal disorders Vomiting	2.3% 1/43 • Number of events 1 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.	0.00% 0/44 • Adverse events were monitored from time of signed informed consent, & within 24 hrs prior to administration of contrast agent (1st exam) until 24 hrs after administration of contrast agent. Repeated for 2nd exam.

Additional Information

Gianpaolo Pirovano, MD, Executive Director, Head Corporate Medical Development

Bracco Diagnostics Inc.

Phone: 609-514-2226

Email: gianpaolo.pirovano@diag.bracco.com

Results disclosure agreements

• Principal investigator is a sponsor employee The results of the study may be presented during scientific symposia or published in a scientific journal only after review by Bracco in accordance with the guidelines set forth in the applicable publication or financial agreement.
• Publication restrictions are in place

Restriction type: OTHER