Central Nervous System Diseases
Conditions
Keywords
disease of the central nervous system (brain or spine)
Brief summary
The purpose of this study was to assess the safety and enhancing properties of the magnetic resonance imaging (MRI) contrast agent MultiHance in children aged 2 to 17 years having central nervous system (CNS) disorders.
Interventions
A dose of 0.10 mmol/kg (i.e., 0.2 mL/kg) of 0.5 molar MultiHance was injected intravenously at a rate of 2 mL/sec as a single dose.
Sponsors
Bracco Diagnostics, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Between 2 and 17 years of age * Informed consent from parents * Assent from patient where required * Known or highly suspected disease of the CNS and referred for either cranial or spinal MRI examination
Exclusion criteria
* Contraindication to MRI * Undergoing MRI in an emergency situation * Known allergy to one or more of the ingredients in MultiHance * Sickle cell anemia moderate to severe renal impairment * Received another investigational compound within 30 days * Pregnancy * Lactating females * Likely to undergo an invasive procedure within 72 hours of receiving MultiHance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 1 | pre-dose and immediately postdose | 5-point scale (0=no delineation of lesion borders \[lesion not identified in image, lesion borders not visible\]; 1=poor border delineation \[all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema\]; 2=moderate border delineation \[border delineation fair/not complete, lesion not clearly separated\]; 3=good border delineation \[border delineation complete, lesion adequately separated\]; 4=excellent border delineation \[borders sharply/clearly distinct, lesion sharply separated\]) paired assessment to compare the difference between pre to pre+postdose |
| Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 2 | pre-dose and immediately postdose | 5-point scale (0=no delineation of lesion borders \[lesion not identified in image, lesion borders not visible\]; 1=poor border delineation \[all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema\]; 2=moderate border delineation \[border delineation fair/not complete, lesion not clearly separated\]; 3=good border delineation \[border delineation complete, lesion adequately separated\]; 4=excellent border delineation \[borders sharply/clearly distinct, lesion sharply separated\]) paired assessment to compare the difference between pre to pre+postdose |
| Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 3 | pre-dose and immediately postdose | 5-point scale (0=no delineation of lesion borders \[lesion not identified in image, lesion borders not visible\]; 1=poor border delineation \[all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema\]; 2=moderate border delineation \[border delineation fair/not complete, lesion not clearly separated\]; 3=good border delineation \[border delineation complete, lesion adequately separated\]; 4=excellent border delineation \[borders sharply/clearly distinct, lesion sharply separated\]) paired assessment to compare the difference between pre to pre+postdose |
| Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 1 | pre-dose to immediately post dose | 5-point scale (0=no visualization of lesion internal morphology (LIM) \[lesion not identified in image, not visible\]; 1=poor visualization of LIM \[insufficiently depicted, intralesional features poorly identified\]; 2=moderate visualization of LIM \[not completely depicted, some intralesional features visible\]; 3=good visualization of LIM \[completely depicted, intralesional features adequately identified\]; 4=excellent visualization of LIM \[optimally depicted, intralesional features clearly identified and characterized\]) paired assessment to compare the difference between pre to pre+postdose |
| Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 2 | pre-dose to immediately post dose | 5-point scale (0=no visualization of lesion internal morphology (LIM) \[lesion not identified in image, not visible\]; 1=poor visualization of LIM \[insufficiently depicted, intralesional features poorly identified\]; 2=moderate visualization of LIM \[not completely depicted, some intralesional features visible\]; 3=good visualization of LIM \[completely depicted, intralesional features adequately identified\]; 4=excellent visualization of LIM \[optimally depicted, intralesional features clearly identified and characterized\]) paired assessment to compare the difference between pre to pre+postdose |
| Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 3 | pre-dose to immediately postdose | 5-point scale (0=no visualization of lesion internal morphology (LIM) \[lesion not identified in image, not visible\]; 1=poor visualization of LIM \[insufficiently depicted, intralesional features poorly identified\]; 2=moderate visualization of LIM \[not completely depicted, some intralesional features visible\]; 3=good visualization of LIM \[completely depicted, intralesional features adequately identified\]; 4=excellent visualization of LIM \[optimally depicted, intralesional features clearly identified and characterized\]) paired assessment to compare the difference between pre to pre+postdose |
| Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 1 | pre-dose and immediately postdose | 5-point scale (0=no lesion CE \[lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue\]; 1=poor lesion CE \[diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size\]; 2=moderate lesion CE \[diff. in SI fair, lesion identified, not possible to evaluate/measure size\]; 3=good lesion CE \[diff. in SI adequate, lesion identified, size evaluated/measured\]; 4=excellent lesion CE \[diff. in SI marked, lesion identified, size measured\]) paired assessment to compare the diff. between pre to pre+postdose |
| Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 2 | pre-dose to immediately postdose | 5-point scale (0=no lesion CE \[lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue\]; 1=poor lesion CE \[diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size\]; 2=moderate lesion CE \[diff. in SI fair, lesion identified, not possible to evaluate/measure size\]; 3=good lesion CE \[diff. in SI adequate, lesion identified, size evaluated/measured\]; 4=excellent lesion CE \[diff. in SI marked, lesion identified, size measured\]) paired assessment to compare the diff. between pre to pre+postdose |
| Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 3 | pre-dose to immediately postdose | 5-point scale (0=no lesion CE \[lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue\]; 1=poor lesion CE \[diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size\]; 2=moderate lesion CE \[diff. in SI fair, lesion identified, not possible to evaluate/measure size\]; 3=good lesion CE \[diff. in SI adequate, lesion identified, size evaluated/measured\]; 4=excellent lesion CE \[diff. in SI marked, lesion identified, size measured\]) paired assessment to compare the diff. between pre to pre+postdose |
| The Number of Patients Administered MultiHance (Gadobenate Dimeglumine) Reporting Adverse Events | up to 72 hours post dose | — |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from April 2006 to July 2008 at 17 investigational sites. The blinded read was conducted from September 12, 2008 to September 26, 2008.
Pre-assignment details
94 patients enrolled; 92 patients dosed.
Participants by arm
| Arm | Count |
|---|---|
| Gadobenate Dimeglumine Contrast Agent, 0.10 mmol/kg injection | 92 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | a parent refused blood draw | 1 |
| Overall Study | did not complete the 24-hr f-up visit | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Gadobenate Dimeglumine |
|---|---|
| Age, Categorical <=18 years | 92 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 10.59 years STANDARD_DEVIATION 4.017 |
| Region of Enrollment Canada | 1 participants |
| Region of Enrollment China | 9 participants |
| Region of Enrollment Europe | 47 participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 92 |
| serious Total, serious adverse events | 0 / 92 |
Outcome results
Primary
Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 1
5-point scale (0=no delineation of lesion borders \[lesion not identified in image, lesion borders not visible\]; 1=poor border delineation \[all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema\]; 2=moderate border delineation \[border delineation fair/not complete, lesion not clearly separated\]; 3=good border delineation \[border delineation complete, lesion adequately separated\]; 4=excellent border delineation \[borders sharply/clearly distinct, lesion sharply separated\]) paired assessment to compare the difference between pre to pre+postdose
Time frame: pre-dose 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 1 | Predose | 1.7 Units on a Scale (0 to 4) | Standard Deviation 1.16 |
| Gadobenate Dimeglumine | Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 1 | Pre+Postdose | 3.0 Units on a Scale (0 to 4) | Standard Deviation 1.2 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [1.1, 1.5]t-test, 2 sided
Primary
Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 2
5-point scale (0=no delineation of lesion borders \[lesion not identified in image, lesion borders not visible\]; 1=poor border delineation \[all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema\]; 2=moderate border delineation \[border delineation fair/not complete, lesion not clearly separated\]; 3=good border delineation \[border delineation complete, lesion adequately separated\]; 4=excellent border delineation \[borders sharply/clearly distinct, lesion sharply separated\]) paired assessment to compare the difference between pre to pre+postdose
Time frame: pre-dose 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 2 | Predose | 1.9 Units on a Scale (0 to 4) | Standard Deviation 1.15 |
| Gadobenate Dimeglumine | Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 2 | Pre+Postdose | 3.1 Units on a Scale (0 to 4) | Standard Deviation 1.11 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [0.9, 1.4]t-test, 2 sided
Primary
Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 3
5-point scale (0=no delineation of lesion borders \[lesion not identified in image, lesion borders not visible\]; 1=poor border delineation \[all borders poorly distinct, lesion not separated from surrounding tissues/structures/edema\]; 2=moderate border delineation \[border delineation fair/not complete, lesion not clearly separated\]; 3=good border delineation \[border delineation complete, lesion adequately separated\]; 4=excellent border delineation \[borders sharply/clearly distinct, lesion sharply separated\]) paired assessment to compare the difference between pre to pre+postdose
Time frame: pre-dose 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 3 | Predose | 1.7 Units on a Scale (0 to 4) | Standard Deviation 1.19 |
| Gadobenate Dimeglumine | Delineation of Lesion Border (Change From Pre to Pre+Postdose) for Reader 3 | Pre+Postdose | 2.4 Units on a Scale (0 to 4) | Standard Deviation 1.12 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [0.4, 0.9]t-test, 2 sided
Primary
Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 1
5-point scale (0=no lesion CE \[lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue\]; 1=poor lesion CE \[diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size\]; 2=moderate lesion CE \[diff. in SI fair, lesion identified, not possible to evaluate/measure size\]; 3=good lesion CE \[diff. in SI adequate, lesion identified, size evaluated/measured\]; 4=excellent lesion CE \[diff. in SI marked, lesion identified, size measured\]) paired assessment to compare the diff. between pre to pre+postdose
Time frame: pre-dose 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 1 | Pre+Postdose | 3.0 Units on a Scale (0 to 4) | Standard Deviation 1.19 |
| Gadobenate Dimeglumine | Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 1 | Predose | 1.8 Units on a Scale (0 to 4) | Standard Deviation 1.16 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [1, 1.5]t-test, 2 sided
Primary
Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 2
5-point scale (0=no lesion CE \[lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue\]; 1=poor lesion CE \[diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size\]; 2=moderate lesion CE \[diff. in SI fair, lesion identified, not possible to evaluate/measure size\]; 3=good lesion CE \[diff. in SI adequate, lesion identified, size evaluated/measured\]; 4=excellent lesion CE \[diff. in SI marked, lesion identified, size measured\]) paired assessment to compare the diff. between pre to pre+postdose
Time frame: pre-dose to 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 2 | Predose | 2.0 Units on a Scale (0 to 4) | Standard Deviation 1.2 |
| Gadobenate Dimeglumine | Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 2 | Pre+Postdose | 3.2 Units on a Scale (0 to 4) | Standard Deviation 1.12 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [0.9, 1.4]t-test, 2 sided
Primary
Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 3
5-point scale (0=no lesion CE \[lesion not identified in image, no contrast between lesion and surrounding normal brain/spine tissue\]; 1=poor lesion CE \[diff. in signal intensity (SI) poor, lesion barely identified, not possible to evaluate/measure size\]; 2=moderate lesion CE \[diff. in SI fair, lesion identified, not possible to evaluate/measure size\]; 3=good lesion CE \[diff. in SI adequate, lesion identified, size evaluated/measured\]; 4=excellent lesion CE \[diff. in SI marked, lesion identified, size measured\]) paired assessment to compare the diff. between pre to pre+postdose
Time frame: pre-dose to 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 3 | Predose | 1.4 Units on a Scale (0 to 4) | Standard Deviation 0.96 |
| Gadobenate Dimeglumine | Lesion Contrast Enhancement (CE) (Change From Pre to Pre+Postdose) for Reader 3 | Pre+Postdose | 2.2 Units on a Scale (0 to 4) | Standard Deviation 1.41 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [0.6, 1.1]t-test, 2 sided
Primary
The Number of Patients Administered MultiHance (Gadobenate Dimeglumine) Reporting Adverse Events
Time frame: up to 72 hours post dose
Population: Included all dosed patients (safety population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Gadobenate Dimeglumine | The Number of Patients Administered MultiHance (Gadobenate Dimeglumine) Reporting Adverse Events | 8 Participants |
Primary
Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 1
5-point scale (0=no visualization of lesion internal morphology (LIM) \[lesion not identified in image, not visible\]; 1=poor visualization of LIM \[insufficiently depicted, intralesional features poorly identified\]; 2=moderate visualization of LIM \[not completely depicted, some intralesional features visible\]; 3=good visualization of LIM \[completely depicted, intralesional features adequately identified\]; 4=excellent visualization of LIM \[optimally depicted, intralesional features clearly identified and characterized\]) paired assessment to compare the difference between pre to pre+postdose
Time frame: pre-dose to immediately post dose
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 1 | Predose | 1.9 Units on a Scale (0 to 4) | Standard Deviation 1.18 |
| Gadobenate Dimeglumine | Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 1 | Pre+Postdose | 3.2 Units on a Scale (0 to 4) | Standard Deviation 1.19 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.00195% CI: [1.1, 1.6]t-test, 2 sided
Primary
Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 2
5-point scale (0=no visualization of lesion internal morphology (LIM) \[lesion not identified in image, not visible\]; 1=poor visualization of LIM \[insufficiently depicted, intralesional features poorly identified\]; 2=moderate visualization of LIM \[not completely depicted, some intralesional features visible\]; 3=good visualization of LIM \[completely depicted, intralesional features adequately identified\]; 4=excellent visualization of LIM \[optimally depicted, intralesional features clearly identified and characterized\]) paired assessment to compare the difference between pre to pre+postdose
Time frame: pre-dose to immediately post dose
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 2 | Predose | 2.1 Units on a Scale (0 to 4) | Standard Deviation 1.17 |
| Gadobenate Dimeglumine | Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 2 | Pre+Postdose | 3.2 Units on a Scale (0 to 4) | Standard Deviation 1.13 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.00195% CI: [0.8, 1.4]t-test, 2 sided
Primary
Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 3
5-point scale (0=no visualization of lesion internal morphology (LIM) \[lesion not identified in image, not visible\]; 1=poor visualization of LIM \[insufficiently depicted, intralesional features poorly identified\]; 2=moderate visualization of LIM \[not completely depicted, some intralesional features visible\]; 3=good visualization of LIM \[completely depicted, intralesional features adequately identified\]; 4=excellent visualization of LIM \[optimally depicted, intralesional features clearly identified and characterized\]) paired assessment to compare the difference between pre to pre+postdose
Time frame: pre-dose to 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobenate Dimeglumine | Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 3 | Predose | 1.4 Units on a Scale (0 to 4) | Standard Deviation 1.06 |
| Gadobenate Dimeglumine | Visualization of Lesion Internal Morphology (Change From Pre to Pre+Postdose) for Reader 3 | Pre+Postdose | 2.0 Units on a Scale (0 to 4) | Standard Deviation 1.23 |
Comparison: Paired t-test to compare change from pre to pre+postdosep-value: <0.000195% CI: [0.4, 0.8]t-test, 2 sided