CNS Lesion, Blood Brain Barrier Defect
Conditions
Brief summary
This trial aimed to evaluate the Efficacy and Safety of gadopiclenol for Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)
Detailed description
The purpose of this trial was to evaluate a new gadolinium-based contrast agent (GBCA) gadopiclenol injection for Central Nervous System (CNS) lesion detection and visualization by conventional steady-state CNS imaging. This is a multi-center, international, prospective, double-blind, randomized, controlled, cross-over with comparator trial in male and female patients presenting with known or highly suspected CNS lesion(s) with focal areas of disrupted Blood Brain Barrier (BBB) (e.g., primary and secondary tumors) who are scheduled to undergo a routine contrast-enhanced Magnetic Resonance Imaging (MRI) of the CNS. This trial was conducted in 33 centers worldwide. During the course of the trial, two MRIs were obtained from each patient: one unenhanced and gadopiclenol-enhanced MRI; and one unenhanced and gadobutrol-enhanced MRI. MRI evaluations were performed by on-site investigators and three independent off-site blinded readers.
Interventions
DRUGgadopiclenol
single intravenous (IV) bolus injection at a rate of 2ml/second
DRUGGadobutrol 1Mmol/mL Solution for Injection Vial
single intravenous (IV) bolus injection at a rate of 2ml/second
Sponsors
Guerbet
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient presenting with known or highly suspected CNS lesion(s) with focal areas of disrupted Blood Brain Barrier (BBB) (e.g., primary and secondary tumors) based on results of a previous imaging procedure such as Computed Tomography (CT) or MRI, which should have been performed within 12 months prior to ICF signature.
Exclusion criteria
* Patient presenting with acute or chronic renal insufficiency, defined as an estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m² assessed within 1 day prior to each contrast agent injection * Patient presenting extra cranial lesions and/or extra-dural lesions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI. | The lesion visualization (per patient) was based on 3 co-primary criteria on marching lesions: border delineation, internal morphology and degree of contrast enhancement, assessed on the images acquired during the MRI performed with gadopiclenol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor \[internal morphology\] or none \[border delineation, contrast enhancement\], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each co-criterion was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between Paired \[unenhanced and contrast-enhanced\] images and Pre-contrast \[unenhanced\] images was calculated for each of the 3 co-primary criteria and for each reader. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | At each of two MRI examinations with an interval of 2-14 days between 2 MRI examinations | The lesion visualization (per patient) was based on 3 co-primary criteria: border delineation, internal morphology and degree of contrast enhancement, assessed on the images performed with gadopiclenol and images performed with gadobutrol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor \[internal morphology\] or none \[border delineation, contrast enhancement\], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each of the 3 lesion visualization co-criteria was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between gadopiclenol scores mean and gadobutrol scores mean was calculated for each of the 3 co-primary criteria and for each reader. |
Countries
Belgium, France, Germany, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, United States
Participant flow
Pre-assignment details
Among the 260 screened patients, 4 were screen failed. A total of 256 patients were randomized (128 in each arm), of whom 6 discontinued the trial before receiving the first contrast agent. Then 250 patients (125 in each arm) received the first contrast agent and underwent the first MRI (First MRI Period). After a washout period of 2-14 days (Washout Period), 242 patients (120 in the Arm 1 and 122 in the Arm 2) received the second contrast agent and underwent the second MRI (Second MRI Period).
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI Cross-over study design
For Arm 1, the patient performed the first contrast-enhanced MRI with gadopiclenol as contrast agent. After a washout period of 2-14 days, the patient performed the second contrast-enhanced MRI with gadobutrol as contrast agent.
For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadopiclenol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadobutrol-enhanced MR Images obtained in the Second MRI Examination Period . | 119 |
| Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI Cross-over study design
For Arm 2, the patient performed the first contrast-enhanced MRI with gadobutrol as contrast agent. After a washout period of 2-14 days, the patient performed the second contrast-enhanced MRI with gadopiclenol as contrast agent.
For each patient, two sets of MR images per MRI examination were obtained : unenhanced and gadobutrol-enhanced MR images obtained in the First MRI Examination Period, unenhanced and gadopiclenol-enhanced MR images obtained in the Second MRI Examination Period. | 120 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First MRI Examination | Adverse Event | 2 | 0 |
| First MRI Examination | Protocol Violation | 0 | 1 |
| First MRI Examination | Withdrawal by Subject | 1 | 2 |
| Washout | Adverse Event | 2 | 0 |
| Washout | Follow-up unavailable due to COVID-19 pandemic | 2 | 1 |
| Washout | Other reason | 1 | 1 |
| Washout | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Arm 1: Gadopiclenol-enhanced MRI for First MRI and Gadobutrol-enhanced MRI for Second MRI | Total | Arm 2: Gadobutrol-enhanced MRI for First MRI and Gadopiclenol-enhanced MRI for Second MRI |
|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 13.4 | 57.2 years STANDARD_DEVIATION 13.8 | 56.1 years STANDARD_DEVIATION 14.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 17 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 113 Participants | 222 Participants | 109 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 5 Participants | 16 Participants | 11 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 18 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 101 Participants | 199 Participants | 98 Participants |
| Region of Enrollment Belgium | 2 participants | 2 participants | 0 participants |
| Region of Enrollment France | 2 participants | 6 participants | 4 participants |
| Region of Enrollment Germany | 1 participants | 3 participants | 2 participants |
| Region of Enrollment Hungary | 57 participants | 100 participants | 43 participants |
| Region of Enrollment Italy | 10 participants | 22 participants | 12 participants |
| Region of Enrollment Mexico | 5 participants | 16 participants | 11 participants |
| Region of Enrollment Poland | 11 participants | 27 participants | 16 participants |
| Region of Enrollment South Korea | 7 participants | 12 participants | 5 participants |
| Region of Enrollment Spain | 5 participants | 6 participants | 1 participants |
| Region of Enrollment Taiwan | 2 participants | 4 participants | 2 participants |
| Region of Enrollment United States | 17 participants | 41 participants | 24 participants |
| Sex: Female, Male Female | 61 Participants | 124 Participants | 63 Participants |
| Sex: Female, Male Male | 58 Participants | 115 Participants | 57 Participants |
| Weight | 77.9 Kg STANDARD_DEVIATION 19.5 | 78.1 Kg STANDARD_DEVIATION 20.1 | 78.4 Kg STANDARD_DEVIATION 20.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 247 | 1 / 245 |
| other Total, other adverse events | 36 / 247 | 42 / 245 |
| serious Total, serious adverse events | 0 / 247 | 1 / 245 |
Outcome results
Primary
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI
The lesion visualization (per patient) was based on 3 co-primary criteria on marching lesions: border delineation, internal morphology and degree of contrast enhancement, assessed on the images acquired during the MRI performed with gadopiclenol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor \[internal morphology\] or none \[border delineation, contrast enhancement\], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each co-criterion was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between Paired \[unenhanced and contrast-enhanced\] images and Pre-contrast \[unenhanced\] images was calculated for each of the 3 co-primary criteria and for each reader.
Time frame: At first MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 1. At second MRI examination (gadopiclenol-enhanced MRI) for patients of Arm 2, performed 2-14 days after gadobutrol-enhanced MRI.
Population: Full Analysis Set (FAS) included a total of 239 patients who had both Pre and Paired images with gadopiclenol assessable for primary criteria for at least one matching lesion for at least one off-site reader: 119 patients in the Arm 1 for whom gadopiclenol-enhanced MRI was performed as first MRI, and 120 patients in the Arm 2 for whom gadopiclenol-enhanced MRI was performed as second MRI. The analysis was based on participants (per patient).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Border delineation - Reader 2 | 3.64 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Internal morphology - Reader 3 | 3.97 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Internal morphology - Reader 1 | 3.92 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Contrast enhancement - Reader 1 | 3.77 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Border delineation - Reader 3 | 3.97 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Contrast enhancement - Reader 2 | 3.58 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Internal morphology - Reader 2 | 3.65 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Contrast enhancement - Reader 3 | 3.90 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Border delineation - Reader 1 | 3.90 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Contrast enhancement - Reader 3 | 1.00 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Border delineation - Reader 1 | 2.08 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Border delineation - Reader 2 | 1.74 mean of a score (on a scale) per patient | Standard Error 1.9 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Border delineation - Reader 3 | 2.61 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Internal morphology - Reader 1 | 1.66 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Internal morphology - Reader 2 | 1.88 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Internal morphology - Reader 3 | 2.01 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Contrast enhancement - Reader 1 | 1.00 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Unenhanced MRI | Contrast enhancement - Reader 2 | 1.00 mean of a score (on a scale) per patient | Standard Error 0.03 |
Comparison: Criterion: Border delineation; Reader 1. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error set at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously and for at least 2 out of 3 readers.p-value: <0.000195% CI: [1.76, 1.88]t-test, 2 sided
Comparison: Criterion: Border delineation; Reader 2. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [1.81, 2]t-test, 2 sided
Comparison: Criterion: Border delineation; Reader 3. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [1.29, 1.44]t-test, 2 sided
Comparison: Criterion: Internal morphology; Reader 1. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [2.2, 2.33]t-test, 2 sided
Comparison: Criterion: Internal morphology; Reader 2. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [1.69, 1.85]t-test, 2 sided
Comparison: Criterion: Internal morphology; Reader 3. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [1.85, 2.06]t-test, 2 sided
Comparison: Criterion: Contrast enhancement; Reader 1. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [2.69, 2.85]t-test, 2 sided
Comparison: Criterion: Contrast enhancement - Reader 2. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [2.49, 2.67]t-test, 2 sided
Comparison: Criterion: Contrast enhancement; Reader 3. The null hypothesis was that the difference in mean scores between Paired images and Pre-contrast images for each of the 3 co-primary criteria was equal to 0. The Null hypothesis was rejected if the difference was significantly different from zero with a type 1 error at 0.025. To conclude the superiority of gadopiclenol-enhanced MRI, the null hypothesis had to be rejected for all co-criteria simultaneously.p-value: <0.000195% CI: [2.84, 2.95]t-test, 2 sided
Secondary
Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI
The lesion visualization (per patient) was based on 3 co-primary criteria: border delineation, internal morphology and degree of contrast enhancement, assessed on the images performed with gadopiclenol and images performed with gadobutrol by 3 independent readers. The independent blinded reader recorded each of the 3 co-primary criteria for up to 3 most representative lesions, using a 4-point scale (1 = poor \[internal morphology\] or none \[border delineation, contrast enhancement\], 2 = moderate, 3 = good, 4 = excellent). The mean of scores for each patient and for each of the 3 lesion visualization co-criteria was calculated as follows: Mean of scores = score of lesion 1 + score of lesion 2 (if any) + score of lesion 3 (if any) divided by the number of lesions, ranged from 1 to 4. The difference in mean scores on matching lesions between gadopiclenol scores mean and gadobutrol scores mean was calculated for each of the 3 co-primary criteria and for each reader.
Time frame: At each of two MRI examinations with an interval of 2-14 days between 2 MRI examinations
Population: Per-Protocol Set (PPS) analysis population including a total of 236 patients (117 patients of Arm 1 and 119 patients of Arm 2) with no major protocol deviation who have Paired (combined unenhanced and contrast-enhanced) images for both gadopiclenol and gadobutrol assessable for this secondary outcome mesure for at least one matching lesion for at least one off-site reader. The analysis was based on participants (per patient).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Border delineation - Reader 2 | 3.64 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Internal morphology - Reader 3 | 3.97 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Internal morphology - Reader 1 | 3.93 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Contrast enhancement - Reader 1 | 3.78 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Border delineation - Reader 3 | 3.97 mean of a score (on a scale) per patient | Standard Error 0.01 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Contrast enhancement - Reader 2 | 3.57 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Internal morphology - Reader 2 | 3.64 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Contrast enhancement - Reader 3 | 3.89 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Paired Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Border delineation - Reader 1 | 3.91 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Contrast enhancement - Reader 3 | 3.81 mean of a score (on a scale) per patient | Standard Error 0.03 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Border delineation - Reader 1 | 3.93 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Border delineation - Reader 2 | 3.60 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Border delineation - Reader 3 | 3.95 mean of a score (on a scale) per patient | Standard Error 0.01 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Internal morphology - Reader 1 | 3.93 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Internal morphology - Reader 2 | 3.62 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Internal morphology - Reader 3 | 3.92 mean of a score (on a scale) per patient | Standard Error 0.02 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Contrast enhancement - Reader 1 | 3.77 mean of a score (on a scale) per patient | Standard Error 0.04 |
| Patients With Gadopiclenol Pre Images | Lesion Visualization Comparing Gadopiclenol-enhanced MRI to Gadobutrol-enhanced MRI | Contrast enhancement - Reader 2 | 3.52 mean of a score (on a scale) per patient | Standard Error 0.04 |
Comparison: Criterion: Border delineation; Reader 1. The null hypothesis was that the difference in mean scores between gadopiclenol and gadobutrol for each of the 3 primary criteria was equal to the non inferiority margin (-0.35). The alternative hypothesis was that the difference in mean scores between gadopiclenol and gadobutrol for each of the 3 co-primary criteria was greater than the non inferiority margin.p-value: <0.000195% CI: [-0.06, 0.02]t-test, 2 sided
Comparison: Criterion: Border delineation; Reader 2. The null hypothesis was that the difference in mean scores between gadopiclenol and gadobutrol for each of the 3 primary criteria was equal to the non inferiority margin (-0.35). The alternative hypothesis was that the difference in mean scores between gadopiclenol and gadobutrol for each of the 3 co-primary criteria was greater than the non inferiority margin.p-value: <0.000195% CI: [-0.04, 0.11]t-test, 2 sided
Comparison: Criterion: Border delineation; Reader 3p-value: <0.000195% CI: [-0.01, 0.05]t-test, 2 sided
Comparison: Criterion: Internal morphology; Reader 1p-value: <0.000195% CI: [-0.04, 0.03]t-test, 2 sided
Comparison: Criterion: Internal morphology; Reader 2p-value: <0.000195% CI: [-0.05, 0.09]t-test, 2 sided
Comparison: Criterion: Internal morphology; Reader 3p-value: <0.000195% CI: [0.01, 0.08]t-test, 2 sided
Comparison: Criterion: Contrast enhancement; Reader 1p-value: 0.000195% CI: [-0.04, 0.07]t-test, 2 sided
Comparison: Criterion: Contrast enhancement; Reader 2p-value: <0.000195% CI: [-0.03, 0.12]t-test, 2 sided
Comparison: Criterion: Contrast enhancement; Reader 3p-value: <0.000195% CI: [0.03, 0.15]t-test, 2 sided