Central Nervous System Diseases
Conditions
Keywords
Gadovist, Gadavist, Contrast agent, Brain, Spine disease, Magnetic Resonance Imaging
Brief summary
The purpose of this study is to determine if the contrast agent is effective and safe in the Magnetic Resonance Imaging (MRI) of brain or spine diseases in patients of Chinese origin.
Detailed description
The study has previously been posted by Schering AG, Germany. Schering AG, Germany has been renamed to Bayer HealthCare AG, Germany. Bayer HealthCare AG, Germany is the sponsor of the trial.
Interventions
1,0M, intra venous injection at a dose of 0,1 ml/kg BW (= 0,1 mmol Gd/kg BW)
DRUGMagnevist
0,5M, intra venous injection at a dose of 0,2 ml/kg BW (= 0,1 mmol Gd/kg BW)
Sponsors
Bayer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chinese origin, with known or suspected brain or spine diseases
Exclusion criteria
* Pregnancy * Lactation * Conditions interfering with MRI * Allergy to any contrast agent or any drugs * Participation in other trial * Require emergency treatment * Severely impaired liver and kidney functions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast Magnetic Resonance Imaging (MRI) Scan of Central Nervous System (CNS) Lesions | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | CNR = (signal intensity \[SI\] lesion - SI normal tissue) / standard deviation (SD) background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | The number of lesions in the magnetic resonance scans was recorded before and after injection of contrast agent for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4). |
| Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | The change in diagnostic confidence was assessed based on post-contrast compared to pre-contrast scans as improved, unchanged or worsened for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4). |
| Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | The degree of contrast enhancement was recorded on a 4-point scale as follows: 1 = No: lesion is not enhanced. 2 = Moderate: lesion is weakly enhanced. 3 = Good: lesion is clearly enhanced. 4 = Excellent: lesion is clearly and brightly enhanced. In case of more than one lesion, the lesion with maximum enhancement was to be assessed. The change in lesion contrast enhancement was assessed based on post-contrast in comparison to pre-contrast scans for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4). |
| Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | Lesion delineation was recorded on a 4-point scale as follows: 1 = None: no or unclear delineation of the boundary between lesion and surrounding tissue; 2 = Moderate: some aspects of border delineation covered; 3 = Good: almost clear delineation, but not complete on relevant slices; 4 = Excellent: sharp and complete delineation. In case of more than one lesion, the lesion with maximum enhancement was assessed. Change in lesion delineation was assessed based on post-contrast in comparison to pre-contrast scans for investigators and all 3 blinded readers (reader 2, reader 3 and reader 4). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | CNR = (SI lesion - SI normal tissue) / SD background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background. |
| Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | Investigators and blinded readers (reader 2, 3 and 4) were to record the number of lesions in the magnetic resonance scans before and after injection of contrast agent. |
| Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | Investigators and blinded readers (reader 2, 3 and 4= were to record the number of lesions in the magnetic resonance scans before and after injection of contrast agent. |
| Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast) | CNR = (SI lesion - SI normal tissue) / SD background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background. |
Countries
China
Participant flow
Recruitment details
Participants were recruited at specialized study centers if they satisfied the inclusion and exclusion criteria. All had known or suspected central nervous system lesions (including cranial and spinal lesions) with an indication for contrast enhanced magnetic resonance imaging for diagnosis and further treatment.
Pre-assignment details
Of 150 screened participants, 3 were not randomized (2 due to withdrawal of consent, and 1 due to poor physical condition). 147 participants were randomized to either Gadobutrol 0.1 mmol/kg body weight (BW) (72 participants) or Gadopentetate dimeglumine 0.1 mmol/kg BW (75 participants).
Participants by arm
| Arm | Count |
|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) Participant received 0.1 mmol/kg BW Gadobutrol (= 0.1 mL/kg BW by intravenous injection at a rate of 1.0 mL/sec) | 71 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) Participant received 0.1 mmol/kg BW Gadopentetate Dimeglumine (GD) (= 0.2 mL/kg BW by intravenous injection at a rate of 2.0 mL/sec | 75 |
| Total | 146 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Total |
|---|---|---|---|
| Age, Continuous | 42.8 years STANDARD_DEVIATION 12.24 | 43.9 years STANDARD_DEVIATION 10.1 | 43.4 years STANDARD_DEVIATION 11.17 |
| Sex: Female, Male Female | 33 Participants | 42 Participants | 75 Participants |
| Sex: Female, Male Male | 38 Participants | 33 Participants | 71 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 71 | 4 / 75 |
| serious Total, serious adverse events | 0 / 71 | 0 / 75 |
Outcome results
Primary
Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast Magnetic Resonance Imaging (MRI) Scan of Central Nervous System (CNS) Lesions
CNR = (signal intensity \[SI\] lesion - SI normal tissue) / standard deviation (SD) background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Two participants in each treatment group had missing values for signal intensity for central nervous system lesions at pre- and post-contrast and could thus not be considered for evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast Magnetic Resonance Imaging (MRI) Scan of Central Nervous System (CNS) Lesions | 50.41 Contrast to Noise ratio | Standard Deviation 38.448 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast Magnetic Resonance Imaging (MRI) Scan of Central Nervous System (CNS) Lesions | 43.47 Contrast to Noise ratio | Standard Deviation 39.178 |
non-inferiority
Secondary
Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment
The change in diagnostic confidence was assessed based on post-contrast compared to pre-contrast scans as improved, unchanged or worsened for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Investigator - improved | 68 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Investigator - unchanged | 2 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Investigator - worsened | 0 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 2 - improved | 55 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 2 - unchanged | 15 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 2 - worsened | 0 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 3 - improved | 59 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 3 - unchanged | 11 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 3 - worsened | 0 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 4 - improved | 60 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 4 - unchanged | 8 Participants |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 4 - worsened | 2 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 4 - unchanged | 12 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Investigator - improved | 65 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 3 - improved | 61 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Investigator - unchanged | 10 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 4 - improved | 63 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Investigator - worsened | 0 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 3 - unchanged | 14 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 2 - improved | 61 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 4 - worsened | 0 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 2 - unchanged | 14 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 3 - worsened | 0 Participants |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Diagnostic Confidence From Pre- to Post-contrast Magnetic Resonance Imaging by Treatment | Reader 2 - worsened | 0 Participants |
Secondary
Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI
The degree of contrast enhancement was recorded on a 4-point scale as follows: 1 = No: lesion is not enhanced. 2 = Moderate: lesion is weakly enhanced. 3 = Good: lesion is clearly enhanced. 4 = Excellent: lesion is clearly and brightly enhanced. In case of more than one lesion, the lesion with maximum enhancement was to be assessed. The change in lesion contrast enhancement was assessed based on post-contrast in comparison to pre-contrast scans for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Lesion contrast enhancement of 1 participant in the Gadavist group was assessed by the investigator (but not the blinded readers) as 'not applicable'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Investigator | 2.4 Contrast enhancement score | Standard Deviation 0.87 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Reader 2 | 2.1 Contrast enhancement score | Standard Deviation 1.21 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Reader 3 | 1.7 Contrast enhancement score | Standard Deviation 0.98 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Reader 4 | 2.2 Contrast enhancement score | Standard Deviation 1.05 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Reader 4 | 2.1 Contrast enhancement score | Standard Deviation 1.09 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Investigator | 2.2 Contrast enhancement score | Standard Deviation 0.87 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Reader 3 | 1.6 Contrast enhancement score | Standard Deviation 0.89 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Contrast Enhancement From Pre- to Post-contrast MRI | Reader 2 | 2.0 Contrast enhancement score | Standard Deviation 1.22 |
Secondary
Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions
Lesion delineation was recorded on a 4-point scale as follows: 1 = None: no or unclear delineation of the boundary between lesion and surrounding tissue; 2 = Moderate: some aspects of border delineation covered; 3 = Good: almost clear delineation, but not complete on relevant slices; 4 = Excellent: sharp and complete delineation. In case of more than one lesion, the lesion with maximum enhancement was assessed. Change in lesion delineation was assessed based on post-contrast in comparison to pre-contrast scans for investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Lesion contrast enhancement of 1 participant in the Gadavist group was assessed by the investigator (but not the blinded readers) as 'not applicable'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Investigator | 1.1 Lesion delineation score | Standard Deviation 0.73 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Reader 2 | 1.4 Lesion delineation score | Standard Deviation 0.89 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Reader 3 | 0.9 Lesion delineation score | Standard Deviation 0.71 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Reader 4 | 1.0 Lesion delineation score | Standard Deviation 0.81 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Reader 4 | 0.9 Lesion delineation score | Standard Deviation 0.67 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Reader 3 | 0.8 Lesion delineation score | Standard Deviation 0.53 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Reader 2 | 1.3 Lesion delineation score | Standard Deviation 0.88 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Lesion Delineation Between Pre- and Post-contrast MRI Scan of CNS Lesions | Investigator | 1.0 Lesion delineation score | Standard Deviation 0.85 |
Secondary
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan
The number of lesions in the magnetic resonance scans was recorded before and after injection of contrast agent for the investigators and all 3 blinded readers (reader 2, reader 3 and reader 4).
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Investigator | 0.7 Lesions | Standard Deviation 2.56 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Reader 2 | 1.4 Lesions | Standard Deviation 6.94 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Reader 3 | 1.7 Lesions | Standard Deviation 9.72 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Reader 4 | 0.5 Lesions | Standard Deviation 2.72 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Reader 4 | 0.1 Lesions | Standard Deviation 0.93 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Investigator | 0.1 Lesions | Standard Deviation 0.83 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Reader 3 | 0.3 Lesions | Standard Deviation 1.44 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan | Reader 2 | 0.3 Lesions | Standard Deviation 1.87 |
Other Pre-specified
Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
CNR = (SI lesion - SI normal tissue) / SD background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All valid case participants who received contrast injection. Subgroup: those with primary malignant brain tumor(s) / brain metastases. One participant in the Gadavist group had missing values for signal intensity for central nervous system lesions at pre- and post-contrast and could thus not be considered for evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | 54.95 Contrast to Noise ratio | Standard Deviation 42.405 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | 46.56 Contrast to Noise ratio | Standard Deviation 30.074 |
Other Pre-specified
Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
CNR = (SI lesion - SI normal tissue) / SD background. SI lesion is the signal intensity in the lesion, SI normal tissue is the signal intensity in the normal tissue, and SD background is the standard deviation of the background noise. The signal intensity (SI) on the pre-contrast and on the post-contrast MR scans was to be measured in the enhanced lesion, normal tissue and background.
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All valid case participants who received contrast injection. Subgroup: those with CNS lesions other than primary malignant brain tumor(s) / brain metastases. 1 (Gadavist) and 2 participants (Magnevist) had missing values for signal intensity for CNS lesions pre- and post-contrast and could not be considered for evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | 48.51 Contrast to Noise ratio | Standard Deviation 36.985 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Contrast to Noise Ratio (CNR) Between Pre- and Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | 41.86 Contrast to Noise ratio | Standard Deviation 43.379 |
Other Pre-specified
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases
Investigators and blinded readers (reader 2, 3 and 4) were to record the number of lesions in the magnetic resonance scans before and after injection of contrast agent.
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Subgroup: participants with primary malignant brain tumor(s) / brain metastases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Reader 2 | 0.4 Lesions | Standard Deviation 1.75 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Investigator | 0.7 Lesions | Standard Deviation 2.61 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Reader 3 | 0.5 Lesions | Standard Deviation 2.18 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Reader 4 | 0.1 Lesions | Standard Deviation 0.3 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Reader 4 | 0.0 Lesions | Standard Deviation 0.2 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Investigator | 0.4 Lesions | Standard Deviation 1.41 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Reader 2 | 0.2 Lesions | Standard Deviation 0.55 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of CNS Lesions in Participants With Malignant Brain Tumor(s) / Brain Metastases | Reader 3 | 0.2 Lesions | Standard Deviation 0.72 |
Other Pre-specified
Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases
Investigators and blinded readers (reader 2, 3 and 4= were to record the number of lesions in the magnetic resonance scans before and after injection of contrast agent.
Time frame: Immediately before injection (pre-contrast) and 2-5 min after injection (post-contrast)
Population: Per Protocol Set (PPS): All patients who have received contrast injection and are not invalid cases. Subgroup: participants with CNS lesions other than primary malignant brain tumor(s) / brain metastases
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Reader 2 | 1.8 Lesions | Standard Deviation 8.2 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Investigator | 0.7 Lesions | Standard Deviation 2.57 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Reader 3 | 2.2 Lesions | Standard Deviation 11.53 |
| Gadobutrol 0.1 mmol/kg BW (Gadavist, BAY86-4875) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Reader 4 | 0.7 Lesions | Standard Deviation 3.24 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Reader 4 | 0.2 Lesions | Standard Deviation 1.13 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Investigator | 0 Lesions | Standard Deviation 0 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Reader 2 | 0.3 Lesions | Standard Deviation 2.26 |
| GD 0.1 mmol/kg BW (Magnevist, BAY86-4882) | Change in Number of Detected Lesions From Pre- to Post-contrast MRI Scan of Participants With CNS Lesions Other Than Primary Malignant Brain Tumor(s) / Brain Metastases | Reader 3 | 0.3 Lesions | Standard Deviation 1.7 |