Magnetic Resonance Imaging
Conditions
Keywords
Gadolinium, Contrast enhancement, Central nervous system lesion
Brief summary
The study was conducted to gain knowledge about a new dose of a diagnostic drug that is used for contrast-enhanced Magnetic Resonance Imaging (MRI) of the human central nervous system (CNS). MRI can visualize the anatomy of the body and is used to detect medical conditions. Diagnostic drugs like gadobutrol and gadoterate contain an element called gadolinium that is applied to improve the analysability of MRI-images. The purpose of this study was to examine if contrast-enhanced MRI using a reduced dose of the gadolinium-based contrast agent gadobutrol delivers images of similar quality to those obtained when a full dose of the gadolinium-based contrast agent gadoterate was used.
Detailed description
The study was an open-label, multi-center, comparative, cross-over trial in adult patients with known or highly suspected CNS pathology who were referred for imaging of the CNS. The primary objective of the study was to demonstrate the non-inferiority of gadobutrol (0.075 mmol/ kg body weight) to gadoterate (0.1 mmol/ kg body weight).
Interventions
DRUGGadoterate (Dotarem/Clariscan)
Patients received a single dose of 0.5 molar gadoterate (0.1 mmol per kg body weight) intravenously.
Patients received a single dose of 1.0 molar BAY86-4875 (0.075 mmol per kg body weight) intravenously.
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Known or highly suspected central nervous system (CNS) pathology referred for contrast-enhanced MRI of the CNS. * Glomerular filtration rate (eGFR) value ≥ 60 mL/min/1.73m2 derived from a serum creatinine result within four weeks prior to the first study MRI. * Women with negative urine pregnancy test within 1 hour prior to the administration of gadoterate (the first MRI).
Exclusion criteria
* No enhancing lesion visible on the gadoterate-enhanced MRI scan. * Pregnancy or breastfeeding. * Severe cardiovascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Degree of Lesion Contrast Enhancement | Up to 20 days | Degree of lesion contrast enhancement is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced). |
| Lesion Border Delineation | Up to 20 days | Lesion border delineation is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation). |
| Lesion Internal Morphology | Up to 20 days | Lesion internal morphology is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Image Quality | Up to 20 days | Comparison of image quality between gadobutrol and gadoterate detected by 3 blinded Readers (Full Analysis Set). Blinded Readers assessed the image quality of gadobutrol- and gadoterate-enhanced images (randomly assigned as left \[L\] and right \[R\] image positions) according to a 5-point scale (1- Image R is worse; 2 - Image R is slightly worse; 3- Image R is similar; 4 - Image R is slightly better; 5 - Image R is better). After unblinding of data, the above codes were translated into the following scale: -2 = Gadobutrol image set is worse ; -1 = Gadobutrol image set is slightly worse ; 0 = Image sets are the same ; 1 = Gadobutrol image set is slightly better; 2 = Gadobutrol image set is better. Results for the Average Reader are reported below. |
| Number of Lesions Identified | Up to 20 days | Number of lesions identified (up to 10) detected by 3 blinded Readers. The mean (SD) number lesions in the Average Reader for gadobutrol and gadoterate in the Full Analysis Set was reported below. |
| Number of Participants With Treatment-emergent Adverse Events | From the first study drug administration up to 24 hours post injection | Number of subjects with treatment-emergent adverse events (TEAEs) (Safety Analysis Set). TEAEs are defined as any AEs that increase in intensity or that are newly developed during the TE period for Study Period 1 or Study Period 2, where TE period for Study Period 1 goes from the first study drug administration in Study Period 1 to 24 hours post-injection, and TE period for Study Period 2 from the first study drug administration in Study Period 2 to 24 hours post-injection. |
| Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Up to 20 days | Comparison of contrast enhancement utilizing an overall contrast enhancement estimation algorithm (Full Analysis Set). The exploratory algorithm analyzed the overall enhancement by comparing the axial T1w (longitudinal relaxation time-weighted) enhanced images to the T1w unenhanced images. |
| Detection of Malignant Disease | Up to 20 days | The 3 Blinded Readers had to evaluate if the diagnosis resulting from the combined images was malignant disease or not. Each blinded Reader provided a malignant yes/no response. This was compared to the final diagnosis provided by the Investigator. The majority of Readers (2 or 3 Readers agree) was used to calculate sensitivity, specificity, and accuracy - eg. Final Diagnosis - Malignant (Reader 1-yes, Reader 2-no, Reader 3-yes --- Majority Reader yes) - this would be a match for sensitivity. The percentage of sensitivity, specificity, and accuracy of detection of malignant disease detected by 3 blinded Readers, gadobutrol versus gadoterate (Full Analysis Set) is reported below for Majority Readers. |
| Confidence in Diagnosis | Up to 20 days | Diagnostic confidence detected by 3 blinded Readers, gadobutrol vs gadoterate (Full Analysis Set). Blinded Readers rated their confidence in diagnosis according to a 4-point scale (1 - Not confident; 2 - Somewhat confident; 3 - Confident; 4 - Very confident). Results for the Average Reader are reported below. |
Countries
France, Germany, Italy, South Korea, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
Study was conducted at multiple centers in 7 countries between 14 November 2018 (first participant first visit) and 13 March 2020 (last participant last visit).
Pre-assignment details
From 166 participants screened, 9 participants were screening failure and a total of 157 participants were enrolled, 157 received study drug for period 1 however 142 received study drug for period 2.
Participants by arm
| Arm | Count |
|---|---|
| Gadoterate 0.1 mmol/kg BW-Gadobutrol 0.075 mmol/kg BW Participants received gadoterate at the standard dose of 0.1 mmol/kg body weight (BW) by single intravenous (IV) injection in Study Period 1 and gadobutrol at a dose of 0.075 mmol/kg BW by single IV injection in Study Period 2. | 157 |
| Total | 157 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other reason | 4 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Gadoterate 0.1 mmol/kg BW-Gadobutrol 0.075 mmol/kg BW |
|---|---|
| Age, Continuous | 58.9 years STANDARD_DEVIATION 13.3 |
| Age, Customized 85 years and over | 1 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 94 Participants |
| Age, Customized Children (2-11 years) | 0 Participants |
| Age, Customized From 65-84 years | 62 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants |
| Age, Customized In utero | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 19 Participants |
| Race (NIH/OMB) White | 109 Participants |
| Sex: Female, Male Female | 71 Participants |
| Sex: Female, Male Male | 86 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 143 | 0 / 156 |
| other Total, other adverse events | 1 / 143 | 4 / 156 |
| serious Total, serious adverse events | 0 / 143 | 0 / 156 |
Outcome results
Primary
Degree of Lesion Contrast Enhancement
Degree of lesion contrast enhancement is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced).
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Degree of Lesion Contrast Enhancement | Unenhanced | 0.884 Scores on a scale | Standard Deviation 0.252 |
| Gadoterate 0.1 mmol/kg BW | Degree of Lesion Contrast Enhancement | Combined unenhanced/enhanced | 3.007 Scores on a scale | Standard Deviation 0.813 |
| Gadobutrol 0.075 mmol/kg BW | Degree of Lesion Contrast Enhancement | Unenhanced | 0.863 Scores on a scale | Standard Deviation 0.201 |
| Gadobutrol 0.075 mmol/kg BW | Degree of Lesion Contrast Enhancement | Combined unenhanced/enhanced | 2.979 Scores on a scale | Standard Deviation 0.837 |
Comparison: Difference (gadobutrol minus unenhanced) - (gadoterate minus unenhanced)p-value: <0.000195% CI: [0.347, 0.562]Paired t-test
Primary
Lesion Border Delineation
Lesion border delineation is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation).
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Lesion Border Delineation | Unenhanced | 2.279 Scores on a scale | Standard Deviation 0.82 |
| Gadoterate 0.1 mmol/kg BW | Lesion Border Delineation | Combined unenhanced/enhanced | 3.096 Scores on a scale | Standard Deviation 0.781 |
| Gadobutrol 0.075 mmol/kg BW | Lesion Border Delineation | Combined unenhanced/enhanced | 3.099 Scores on a scale | Standard Deviation 0.828 |
| Gadobutrol 0.075 mmol/kg BW | Lesion Border Delineation | Unenhanced | 2.278 Scores on a scale | Standard Deviation 0.864 |
Comparison: Difference (gadobutrol minus unenhanced) - (gadoterate minus unenhanced)p-value: =0.015195% CI: [0.017, 0.342]Paired t-test
Primary
Lesion Internal Morphology
Lesion internal morphology is assessed by 3 blinded Readers (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility)
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Lesion Internal Morphology | Unenhanced | 1.835 Scores on a scale | Standard Deviation 0.62 |
| Gadoterate 0.1 mmol/kg BW | Lesion Internal Morphology | Combined unenhanced/enhanced | 2.503 Scores on a scale | Standard Deviation 0.496 |
| Gadobutrol 0.075 mmol/kg BW | Lesion Internal Morphology | Unenhanced | 1.823 Scores on a scale | Standard Deviation 0.589 |
| Gadobutrol 0.075 mmol/kg BW | Lesion Internal Morphology | Combined unenhanced/enhanced | 2.484 Scores on a scale | Standard Deviation 0.545 |
Comparison: Difference (gadobutrol minus unenhanced) - (gadoterate minus unenhanced)p-value: =0.0195% CI: [0.024, 0.275]Paired t-test
Secondary
Confidence in Diagnosis
Diagnostic confidence detected by 3 blinded Readers, gadobutrol vs gadoterate (Full Analysis Set). Blinded Readers rated their confidence in diagnosis according to a 4-point scale (1 - Not confident; 2 - Somewhat confident; 3 - Confident; 4 - Very confident). Results for the Average Reader are reported below.
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All subjects for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Confidence in Diagnosis | 3.272 Scores on a scale | Standard Deviation 0.567 |
| Gadobutrol 0.075 mmol/kg BW | Confidence in Diagnosis | 3.348 Scores on a scale | Standard Deviation 0.591 |
Comparison: Difference (Gadobutrol - Gadoterate)95% CI: [0.011, 0.14]
Secondary
Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm
Comparison of contrast enhancement utilizing an overall contrast enhancement estimation algorithm (Full Analysis Set). The exploratory algorithm analyzed the overall enhancement by comparing the axial T1w (longitudinal relaxation time-weighted) enhanced images to the T1w unenhanced images.
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Relative score | 0.19894 Scores on a scale | Standard Deviation 0.09905 |
| Gadoterate 0.1 mmol/kg BW | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Full image score | 0.05604 Scores on a scale | Standard Deviation 0.08581 |
| Gadoterate 0.1 mmol/kg BW | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Dice score | 0.92984 Scores on a scale | Standard Deviation 0.04293 |
| Gadobutrol 0.075 mmol/kg BW | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Relative score | 0.18564 Scores on a scale | Standard Deviation 0.09028 |
| Gadobutrol 0.075 mmol/kg BW | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Full image score | 0.05573 Scores on a scale | Standard Deviation 0.08036 |
| Gadobutrol 0.075 mmol/kg BW | Contrast Enhancement Utilizing an Exploratory Overall Contrast Enhancement Estimation Algorithm | Dice score | 0.92991 Scores on a scale | Standard Deviation 0.05216 |
Comparison: Difference (Gadobutrol-Gadoterate) for Relative score95% CI: [-0.03491, -0.00445]
Comparison: Difference (Gadobutrol-Gadoterate) for Full image score95% CI: [-0.00589, 0.01762]
Comparison: Difference (Gadobutrol-Gadoterate) for Dice score95% CI: [-0.00471, 0.00749]
Secondary
Detection of Malignant Disease
The 3 Blinded Readers had to evaluate if the diagnosis resulting from the combined images was malignant disease or not. Each blinded Reader provided a malignant yes/no response. This was compared to the final diagnosis provided by the Investigator. The majority of Readers (2 or 3 Readers agree) was used to calculate sensitivity, specificity, and accuracy - eg. Final Diagnosis - Malignant (Reader 1-yes, Reader 2-no, Reader 3-yes --- Majority Reader yes) - this would be a match for sensitivity. The percentage of sensitivity, specificity, and accuracy of detection of malignant disease detected by 3 blinded Readers, gadobutrol versus gadoterate (Full Analysis Set) is reported below for Majority Readers.
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All subjects for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Detection of Malignant Disease | Specificity | 91.8 Percentage (%) |
| Gadoterate 0.1 mmol/kg BW | Detection of Malignant Disease | Sensitivity | 58.7 Percentage (%) |
| Gadoterate 0.1 mmol/kg BW | Detection of Malignant Disease | Accuracy | 70.2 Percentage (%) |
| Gadobutrol 0.075 mmol/kg BW | Detection of Malignant Disease | Sensitivity | 58.7 Percentage (%) |
| Gadobutrol 0.075 mmol/kg BW | Detection of Malignant Disease | Specificity | 91.8 Percentage (%) |
| Gadobutrol 0.075 mmol/kg BW | Detection of Malignant Disease | Accuracy | 70.2 Percentage (%) |
Comparison: Accuracy Difference (Gadobutrol - Gadoterate)95% CI: [-3.4, 3.4]
Comparison: Sensitivity Difference (Gadobutrol - Gadoterate)95% CI: [-5.22, 5.22]
Comparison: Specificity Difference (Gadobutrol - Gadoterate)95% CI: [0, 0]
Secondary
Image Quality
Comparison of image quality between gadobutrol and gadoterate detected by 3 blinded Readers (Full Analysis Set). Blinded Readers assessed the image quality of gadobutrol- and gadoterate-enhanced images (randomly assigned as left \[L\] and right \[R\] image positions) according to a 5-point scale (1- Image R is worse; 2 - Image R is slightly worse; 3- Image R is similar; 4 - Image R is slightly better; 5 - Image R is better). After unblinding of data, the above codes were translated into the following scale: -2 = Gadobutrol image set is worse ; -1 = Gadobutrol image set is slightly worse ; 0 = Image sets are the same ; 1 = Gadobutrol image set is slightly better; 2 = Gadobutrol image set is better. Results for the Average Reader are reported below.
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Image Quality | 0.00 Scores on a scale | Standard Deviation 0.61 |
Comparison: Comparison of image quality between gadobutrol and gadoteratep-value: 0.914995% CI: [-0.1, 0.11]Wilcoxon signed-rank test
Secondary
Number of Lesions Identified
Number of lesions identified (up to 10) detected by 3 blinded Readers. The mean (SD) number lesions in the Average Reader for gadobutrol and gadoterate in the Full Analysis Set was reported below.
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All subjects for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Number of Lesions Identified | 2.064 Number of lesions identified | Standard Deviation 2.254 |
| Gadobutrol 0.075 mmol/kg BW | Number of Lesions Identified | 2.137 Number of lesions identified | Standard Deviation 2.327 |
Comparison: Difference (Gadobutrol - Gadoterate)95% CI: [-0.03, 0.176]
Secondary
Number of Participants With Treatment-emergent Adverse Events
Number of subjects with treatment-emergent adverse events (TEAEs) (Safety Analysis Set). TEAEs are defined as any AEs that increase in intensity or that are newly developed during the TE period for Study Period 1 or Study Period 2, where TE period for Study Period 1 goes from the first study drug administration in Study Period 1 to 24 hours post-injection, and TE period for Study Period 2 from the first study drug administration in Study Period 2 to 24 hours post-injection.
Time frame: From the first study drug administration up to 24 hours post injection
Population: The Safety analysis set (SAF) included all enrolled participants who received at least 1 study treatment administration.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 4 Participants |
| Gadoterate 0.1 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any study drug-related TEAE | 2 Participants |
| Gadoterate 0.1 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TEAE related to the protocol | 0 Participants |
| Gadoterate 0.1 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TEAE leading to discontinuation | 0 Participants |
| Gadoterate 0.1 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TESAE | 0 Participants |
| Gadoterate 0.1 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | TEAE with outcome death | 0 Participants |
| Gadobutrol 0.075 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TESAE | 0 Participants |
| Gadobutrol 0.075 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TEAE | 1 Participants |
| Gadobutrol 0.075 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TEAE leading to discontinuation | 0 Participants |
| Gadobutrol 0.075 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any study drug-related TEAE | 1 Participants |
| Gadobutrol 0.075 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | TEAE with outcome death | 0 Participants |
| Gadobutrol 0.075 mmol/kg BW | Number of Participants With Treatment-emergent Adverse Events | Any TEAE related to the protocol | 0 Participants |
Post Hoc
Comparison of Border Delineation Detected by Blinded Readers for Combined Image Sets - Equivalence Test
Comparison of border delineation detected by blinded Readers for combined image sets - Equivalence Test (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored the delineation of up to 5 lesions using image sequences and a 4-point scale (1 - None = No or unclear delineation; 2 - Moderate = Partial delineation; 3 - Good = Almost clear, but incomplete delineation; 4 - Excellent = Clear and complete delineation).
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Comparison of Border Delineation Detected by Blinded Readers for Combined Image Sets - Equivalence Test | 3.096 Scores on a scale | Standard Deviation 0.781 |
| Gadobutrol 0.075 mmol/kg BW | Comparison of Border Delineation Detected by Blinded Readers for Combined Image Sets - Equivalence Test | 3.099 Scores on a scale | Standard Deviation 0.828 |
p-value: 0.0013Two one-sided t-tests (TOST)
Post Hoc
Comparison of Degree of Lesion Contrast Enhancement Detected by Blinded Readers for Combined Image Sets - Equivalence Test
Comparison of degree of lesion contrast enhancement detected by blinded Readers for combined image sets - Equivalence Test (Full Analysis Set). Results are presented as the Average Reader score. Blinded Readers scored up to 5 lesions using image sequences and a 4-point scale (1 - No = Lesion not enhanced; 2 - Moderate = Lesion weakly enhanced; 3 - Good = Lesion clearly enhanced; 4 - Excellent = Lesion clearly and brightly enhanced).
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Comparison of Degree of Lesion Contrast Enhancement Detected by Blinded Readers for Combined Image Sets - Equivalence Test | 3.007 Scores on a scale | Standard Deviation 0.813 |
| Gadobutrol 0.075 mmol/kg BW | Comparison of Degree of Lesion Contrast Enhancement Detected by Blinded Readers for Combined Image Sets - Equivalence Test | 2.979 Scores on a scale | Standard Deviation 0.837 |
p-value: 0.0049Two one-sided t-tests (TOST)
Post Hoc
Comparison of Internal Morphology Detected by Blinded Readers for Combined Image Sets - Equivalence Test
Comparison of internal morphology detected by blinded Readers for combined image sets - Equivalence Test (Full Analysis Set). Results are presented as the average Reader score. Blinded Readers scored the structure and internal morphology of up to 5 lesions using image sequences and a 3-point scale (1 - Poor = Poor visibility; 2 - Moderate = Partial visibility; 3 - Good = Sufficient visibility).
Time frame: Up to 20 days
Population: Full analysis set (FAS) was used for analysis, which is defined as All participants for whom electronic case report form (eCRF) entries and images are available for unenhanced MRI, combined unenhanced and gadobutrol enhanced MRI, and combined unenhanced and gadoterate enhanced MRI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gadoterate 0.1 mmol/kg BW | Comparison of Internal Morphology Detected by Blinded Readers for Combined Image Sets - Equivalence Test | 2.503 Scores on a scale | Standard Deviation 0.496 |
| Gadobutrol 0.075 mmol/kg BW | Comparison of Internal Morphology Detected by Blinded Readers for Combined Image Sets - Equivalence Test | 2.484 Scores on a scale | Standard Deviation 0.545 |
p-value: 0.0065Two one-sided t-tests (TOST)