Trial Outcomes & Findings for Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI (NCT NCT01067976)
NCT ID: NCT01067976
Last Updated: 2014-11-11
Results Overview
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value. For ease of expression, the following abbreviations will be used: Magnetic Resonance Mammography (MRM), Unenhanced MRM (UMRM), combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM), X-ray mammography (XRM).
COMPLETED
PHASE3
446 participants
Immediately before injection and after injection
2014-11-11
Participant Flow
Recruitment period: 19 Feb 2010 - 08 Jul 2011.
Participant milestones
| Measure |
Gadobutrol (Gadavist, BAY86-4875)
Participants first received an unenhanced magnetic resonance mammography (MRM), followed by a gadobutrol-enhanced MRM. Gadobutrol was administered at the standard dose of 0.1 mmol/kg body weight (bw) \[0.1 ml/kg bw\] as an intravenous injection (i.v.) at a rate of 2 ml/sec. Unenhanced MRM (UMRM) and combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM) image sets were evaluated in a randomized fashion. After the evaluation of the UMRM or CMRM the respective X-ray mammography (XRM) was added and evaluated together with the UMRM images.
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|---|---|
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Overall Study
STARTED
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446
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|
Overall Study
Received Treatment
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426
|
|
Overall Study
Fulfilled Requirements of FAS Population
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390
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|
Overall Study
COMPLETED
|
424
|
|
Overall Study
NOT COMPLETED
|
22
|
Reasons for withdrawal
| Measure |
Gadobutrol (Gadavist, BAY86-4875)
Participants first received an unenhanced magnetic resonance mammography (MRM), followed by a gadobutrol-enhanced MRM. Gadobutrol was administered at the standard dose of 0.1 mmol/kg body weight (bw) \[0.1 ml/kg bw\] as an intravenous injection (i.v.) at a rate of 2 ml/sec. Unenhanced MRM (UMRM) and combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM) image sets were evaluated in a randomized fashion. After the evaluation of the UMRM or CMRM the respective X-ray mammography (XRM) was added and evaluated together with the UMRM images.
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|---|---|
|
Overall Study
Study drug never administered
|
20
|
|
Overall Study
Study prematurely discontinued
|
2
|
Baseline Characteristics
Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast MRI
Baseline characteristics by cohort
| Measure |
Gadobutrol (Gadavist, BAY86-4875)
n=426 Participants
Participants first received an unenhanced MRM, followed by a gadobutrol-enhanced MRM. Gadobutrol was administered at the standard dose of 0.1 mmol/kg bw \[0.1 ml/kg bw\] as an i.v. injection at a rate of 2 ml/sec. UMRM and CMRM image sets were evaluated in a randomized fashion. After the evaluation of the UMRM or CMRM the respective XRM was added and evaluated together with the UMRM images.
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|---|---|
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Age, Continuous
|
55.5 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
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Sex: Female, Male
Female
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426 Participants
n=5 Participants
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Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
320 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
103 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
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2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian/other Pacific Islander
|
1 participants
n=5 Participants
|
|
Country
Colombia
|
19 participants
n=5 Participants
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|
Country
Finland
|
53 participants
n=5 Participants
|
|
Country
Germany
|
172 participants
n=5 Participants
|
|
Country
Italy
|
25 participants
n=5 Participants
|
|
Country
Korea (South)
|
102 participants
n=5 Participants
|
|
Country
Switzerland
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4 participants
n=5 Participants
|
|
Country
United States
|
51 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 388 participants in the Full Analysis Set (FAS) who had regions with malignant disease verified by Standard of Truth (SOT).
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The difference was calculated as CMRM value minus UMRM value. For ease of expression, the following abbreviations will be used: Magnetic Resonance Mammography (MRM), Unenhanced MRM (UMRM), combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM), X-ray mammography (XRM).
Outcome measures
| Measure |
CMRM vs UMRM
n=388 Participants
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
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Difference for Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 1
|
46.6 difference in sensitivity (%)
Interval 41.9 to 51.4
|
—
|
—
|
—
|
—
|
|
Difference for Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 2
|
30.8 difference in sensitivity (%)
Interval 25.7 to 35.9
|
—
|
—
|
—
|
—
|
|
Difference for Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 3
|
23.3 difference in sensitivity (%)
Interval 19.2 to 27.3
|
—
|
—
|
—
|
—
|
|
Difference for Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Investigator
|
17.8 difference in sensitivity (%)
Interval 14.2 to 21.4
|
—
|
—
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—
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—
|
PRIMARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 388 participants in the Full Analysis Set (FAS) who had regions with malignant disease verified by Standard of Truth (SOT).
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the clinical investigators and the 3 blinded readers using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants.
Outcome measures
| Measure |
CMRM vs UMRM
n=388 Participants
|
CMRM
n=388 Participants
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
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Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 2
|
49.1 sensitivity %
Interval 44.4 to 53.7
|
79.9 sensitivity %
Interval 76.5 to 83.3
|
—
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 3
|
63.4 sensitivity %
Interval 59.1 to 67.8
|
86.7 sensitivity %
Interval 84.1 to 89.4
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—
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Investigator
|
75.9 sensitivity %
Interval 72.1 to 79.8
|
93.8 sensitivity %
Interval 91.9 to 95.6
|
—
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—
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—
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Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 1
|
36.6 sensitivity %
Interval 32.1 to 41.0
|
83.2 sensitivity %
Interval 80.2 to 86.2
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—
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—
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—
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PRIMARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 372 participants in FAS; evaluable for specificity were breasts without malignant disease as verified by Standard of Truth (SOT).
A non-malignant breast was defined as false positive (FP), when the reader assessed at least one breast region as malignant. When all breast regions were assessed as non-malignant, the breast was defined as true negative (TN). Breast level specificity was first defined in participant as number of TN-breasts in participant divided by number of non-malignant breasts in participant. Subsequently the specificity percentage was calculated based on the mean of the specificities across all participants who contributed with at least one non-malignant breast.
Outcome measures
| Measure |
CMRM vs UMRM
n=372 Participants
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Reader 1
|
85.6 specificity (%)
Interval 82.0 to 89.2
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Reader 2
|
95.0 specificity (%)
Interval 92.8 to 97.2
|
—
|
—
|
—
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—
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|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Reader 3
|
88.6 specificity (%)
Interval 85.3 to 91.8
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Investigator
|
95.4 specificity (%)
Interval 93.3 to 97.6
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—
|
—
|
—
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—
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SECONDARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 388 participants in FAS; evaluable for specificity were breasts with malignant disease verified by SoT for which an assessment by the imaging modality was available.
A malignant breast was defined as false positive (FP), when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as true negative (TN). Specificity was then defined as TN/(TN+FP).
Outcome measures
| Measure |
CMRM vs UMRM
n=388 Participants
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Breast Level Specificity of CMRM Based on Malignant Breasts
Reader 1
|
61.1 specificity (%)
Interval 56.3 to 65.9
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM Based on Malignant Breasts
Reader 2
|
59.4 specificity (%)
Interval 54.5 to 64.3
|
—
|
—
|
—
|
—
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|
Breast Level Specificity of CMRM Based on Malignant Breasts
Reader 3
|
58.5 specificity (%)
Interval 53.6 to 63.4
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—
|
—
|
—
|
—
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|
Breast Level Specificity of CMRM Based on Malignant Breasts
Investigator
|
90.3 specificity (%)
Interval 87.4 to 93.3
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—
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—
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—
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—
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SECONDARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 382 participants in FAS. Index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participant eligible for the study.
Index cancer is defined as the cancer confirmed by histology prior to inclusion which made the participants eligible for the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=382 Participants
|
CMRM
n=382 Participants
|
CMRM vs CMRM+XRM
n=382 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
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Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 1
|
47.9 difference in percentage of participants
Interval 42.3 to 53.5
|
11.8 difference in percentage of participants
Interval 6.9 to 16.6
|
0.0 difference in percentage of participants
Interval -1.0 to 1.0
|
—
|
—
|
|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 2
|
30.9 difference in percentage of participants
Interval 24.9 to 36.9
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13.1 difference in percentage of participants
Interval 7.7 to 18.5
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-3.4 difference in percentage of participants
Interval -5.5 to -1.3
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—
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—
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|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 3
|
21.5 difference in percentage of participants
Interval 16.6 to 26.3
|
15.2 difference in percentage of participants
Interval 10.4 to 20.0
|
-0.3 difference in percentage of participants
Interval -1.0 to 0.5
|
—
|
—
|
|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Investigator
|
17.3 difference in percentage of participants
Interval 13.2 to 21.3
|
1.3 difference in percentage of participants
Interval -0.3 to 2.9
|
-0.3 difference in percentage of participants
Interval -1.0 to 0.5
|
—
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—
|
SECONDARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 87 participants in FAS who had at least one additional cancer region according to SoT.
Additional cancer was defined as cancer which was present according to SoT, but which was not defined as index cancer, i.e. was not known when the participant was enrolled into the study. The difference in percentage of participants was calculated as CMRM value minus UMRM value, CMRM value minus XRM value, CMRM value minus CMRM+XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=87 Participants
|
CMRM
n=87 Participants
|
CMRM vs CMRM+XRM
n=87 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Percentage Difference of Participants Whose Additional Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 1
|
42.5 difference in percentage of participants
Interval 30.1 to 55.0
|
36.8 difference in percentage of participants
Interval 24.1 to 49.5
|
-2.3 difference in percentage of participants
Interval -6.6 to 2.0
|
—
|
—
|
|
Percentage Difference of Participants Whose Additional Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 2
|
25.3 difference in percentage of participants
Interval 13.0 to 37.6
|
29.9 difference in percentage of participants
Interval 16.3 to 43.4
|
0.0 difference in percentage of participants
Interval -1.1 to 1.1
|
—
|
—
|
|
Percentage Difference of Participants Whose Additional Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 3
|
37.9 difference in percentage of participants
Interval 24.8 to 51.1
|
31.0 difference in percentage of participants
Interval 17.8 to 44.2
|
0.0 difference in percentage of participants
Interval -1.1 to 1.1
|
—
|
—
|
|
Percentage Difference of Participants Whose Additional Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Investigator
|
31.0 difference in percentage of participants
Interval 20.2 to 41.9
|
49.4 difference in percentage of participants
Interval 37.3 to 61.6
|
0.0 difference in percentage of participants
Interval -1.1 to 1.1
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 390 participants; evaluable for specificity were breasts with or without malignant disease verified by SoT for which assessment by the imaging modality were available.
A non-malignant breast was defined as FP when the reader assessed at least one breast region as malignant. A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as (N-FP)/N, where N was total number of breasts.
Outcome measures
| Measure |
CMRM vs UMRM
n=390 Participants
|
CMRM
n=390 Participants
|
CMRM vs CMRM+XRM
n=390 Participants
|
UMRM+XRM
n=390 Participants
|
CMRM+XRM
n=390 Participants
|
|---|---|---|---|---|---|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Reader 3
|
85.9 specificity (%)
Interval 83.7 to 88.1
|
73.1 specificity (%)
Interval 70.1 to 76.0
|
82.2 specificity (%)
Interval 79.7 to 84.6
|
82.1 specificity (%)
Interval 79.6 to 84.5
|
72.7 specificity (%)
Interval 69.7 to 75.7
|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Reader 1
|
94.0 specificity (%)
Interval 92.4 to 95.6
|
72.6 specificity (%)
Interval 69.5 to 75.6
|
84.1 specificity (%)
Interval 81.5 to 86.7
|
88.6 specificity (%)
Interval 86.4 to 90.8
|
71.9 specificity (%)
Interval 68.8 to 75.1
|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Reader 2
|
89.2 specificity (%)
Interval 87.2 to 91.3
|
76.8 specificity (%)
Interval 74.1 to 79.5
|
87.9 specificity (%)
Interval 85.7 to 90.2
|
83.1 specificity (%)
Interval 80.6 to 85.5
|
76.7 specificity (%)
Interval 74.0 to 79.3
|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Investigator
|
96.5 specificity (%)
Interval 95.2 to 97.9
|
92.4 specificity (%)
Interval 90.4 to 94.4
|
97.8 specificity (%)
Interval 96.7 to 99.0
|
96.2 specificity (%)
Interval 94.7 to 97.6
|
92.3 specificity (%)
Interval 90.3 to 94.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were performed for a total number of 3883 regions, 390 participants in FAS.
For each region the reader chose the category which best described the extent of malignant disease, i.e. no, unifocal, or multifocal malignant breast disease. The proportion of correct matches of each defined image set to the SoT for the extent of malignant breast disease was referred to as the categorical accuracy. The majority read value for the 3 blinded readers was determined at the disease state level (no disease, unifocal, multifocal). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave different categorical determination, the majority reader response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=3883 Breast regions
|
CMRM
n=3883 Breast regions
|
CMRM vs CMRM+XRM
n=3883 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Categorical Accuracy Difference of Extent of Malignant Disease Verified by SoT by Majority Reader, Breast Region Level
|
-1.2 percent difference
Interval -2.4 to 0.0
|
-3.1 percent difference
Interval -4.2 to -2.0
|
-1.5 percent difference
Interval -2.7 to -0.3
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were performed for a total number of 1120 regions, 390 participants from FAS.
For each region the reader chose the category which best described the extent of malignant disease, i.e. no, unifocal, or multifocal malignant breast disease. The proportion of correct matches of each defined image set to the SoT for the extent of malignant breast disease was referred to as the categorical accuracy. The majority read value for the 3 blinded readers was determined at the disease state level (no disease, unifocal, multifocal). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave different categorical determination, the majority reader response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=1120 Breast regions
|
CMRM
n=1120 Breast regions
|
CMRM vs CMRM+XRM
n=1120 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Categorical Accuracy Difference of Extent of Malignant Disease Verified by Histopathology by Majority Reader, Breast Region Level
|
6.3 percent difference
Interval 2.7 to 10.0
|
-2.9 percent difference
Interval -6.0 to 0.3
|
1.2 percent difference
Interval -2.2 to 4.5
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were performed for a total number of 643 regions, 390 participants in FAS. Regions with malignant disease verified by SoT comprise unifocal and multifocal regions.
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for sensitivity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=643 Breast regions
|
CMRM
n=643 Breast regions
|
CMRM vs CMRM+XRM
n=643 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Majority read
|
34.5 difference in sensitivity (%)
Interval 30.2 to 38.8
|
12.3 difference in sensitivity (%)
Interval 9.1 to 15.5
|
17.4 difference in sensitivity (%)
Interval 14.2 to 20.8
|
—
|
—
|
|
Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 1
|
44.3 difference in sensitivity (%)
Interval 39.9 to 48.8
|
14.3 difference in sensitivity (%)
Interval 10.6 to 18.0
|
15.6 difference in sensitivity (%)
Interval 11.8 to 19.3
|
—
|
—
|
|
Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 2
|
30.9 difference in sensitivity (%)
Interval 26.1 to 35.8
|
9.3 difference in sensitivity (%)
Interval 5.6 to 13.0
|
18.5 difference in sensitivity (%)
Interval 14.6 to 22.4
|
—
|
—
|
|
Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 3
|
25.2 difference in sensitivity (%)
Interval 21.2 to 29.2
|
15.1 difference in sensitivity (%)
Interval 11.7 to 18.4
|
17.0 difference in sensitivity (%)
Interval 13.4 to 20.5
|
—
|
—
|
|
Sensitivity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Investigator
|
18.8 difference in sensitivity (%)
Interval 15.0 to 22.6
|
6.5 difference in sensitivity (%)
Interval 3.8 to 9.2
|
10.6 difference in sensitivity (%)
Interval 6.7 to 14.4
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: For unifocal malignant disease, sensitivity analyses were performed for a total number of 576 regions (i.e. regions with unifocal disease verified by SoT), 390 participants in FAS.
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for sensitivity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=576 Breast regions
|
CMRM
n=576 Breast regions
|
CMRM vs CMRM+XRM
n=576 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Majority read
|
24.7 difference in sensitivity (%)
Interval 19.7 to 29.6
|
3.5 difference in sensitivity (%)
Interval -0.7 to 7.6
|
11.8 difference in sensitivity (%)
Interval 7.3 to 16.3
|
—
|
—
|
|
Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 1
|
35.4 difference in sensitivity (%)
Interval 30.2 to 40.6
|
6.6 difference in sensitivity (%)
Interval 2.0 to 11.2
|
14.8 difference in sensitivity (%)
Interval 10.0 to 19.5
|
—
|
—
|
|
Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 2
|
6.8 difference in sensitivity (%)
Interval 1.3 to 12.3
|
-10 difference in sensitivity (%)
Interval -15.0 to -5.0
|
-8.2 difference in sensitivity (%)
Interval -14.0 to -2.7
|
—
|
—
|
|
Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 3
|
20.1 difference in sensitivity (%)
Interval 15.6 to 24.7
|
10.6 difference in sensitivity (%)
Interval 6.4 to 14.7
|
21.2 difference in sensitivity (%)
Interval 16.6 to 25.7
|
—
|
—
|
|
Sensitivity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Investigator
|
9.5 difference in sensitivity (%)
Interval 5.2 to 13.9
|
0.2 difference in sensitivity (%)
Interval -3.0 to 3.4
|
0.9 difference in sensitivity (%)
Interval -3.0 to 4.8
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: For multifocal malignant disease, sensitivity analyses were performed for a total number of 67 regions.
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for sensitivity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=67 Breast regions
|
CMRM
n=67 Breast regions
|
CMRM vs CMRM+XRM
n=67 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Majority read
|
31.3 difference in sensitivity (%)
Interval 18.0 to 44.7
|
28.4 difference in sensitivity (%)
Interval 13.3 to 43.4
|
17.9 difference in sensitivity (%)
Interval 2.4 to 33.4
|
—
|
—
|
|
Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 1
|
26.9 difference in sensitivity (%)
Interval 15.2 to 38.6
|
22.4 difference in sensitivity (%)
Interval 9.7 to 35.0
|
10.4 difference in sensitivity (%)
Interval -4.2 to 25.1
|
—
|
—
|
|
Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 2
|
41.8 difference in sensitivity (%)
Interval 29.3 to 54.3
|
34.3 difference in sensitivity (%)
Interval 22.1 to 46.5
|
40.3 difference in sensitivity (%)
Interval 27.8 to 52.8
|
—
|
—
|
|
Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 3
|
28.4 difference in sensitivity (%)
Interval 15.9 to 40.8
|
23.9 difference in sensitivity (%)
Interval 11.1 to 36.6
|
11.9 difference in sensitivity (%)
Interval -3.3 to 27.2
|
—
|
—
|
|
Sensitivity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Investigator
|
20.9 difference in sensitivity (%)
Interval 10.6 to 31.2
|
13.4 difference in sensitivity (%)
Interval 4.5 to 22.4
|
22.4 difference in sensitivity (%)
Interval 11.8 to 32.9
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were performed for a total number of 3240 regions, 390 participants in FAS.
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for specificity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority reader response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=3240 Breast regions
|
CMRM
n=3240 Breast regions
|
CMRM vs CMRM+XRM
n=3240 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Majority read
|
-6.5 difference in specificity (%)
Interval -7.5 to -5.5
|
-4.9 difference in specificity (%)
Interval -5.9 to -4.0
|
-4.3 difference in specificity (%)
Interval -5.3 to -3.2
|
—
|
—
|
|
Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 1
|
-8.6 difference in specificity (%)
Interval -9.9 to -7.4
|
-6.6 difference in specificity (%)
Interval -7.9 to -5.4
|
-4.9 difference in specificity (%)
Interval -6.3 to -3.6
|
—
|
—
|
|
Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 2
|
-5.6 difference in specificity (%)
Interval -6.8 to -4.4
|
-3.2 difference in specificity (%)
Interval -4.4 to -2.1
|
-5.2 difference in specificity (%)
Interval -6.4 to -4.1
|
—
|
—
|
|
Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 3
|
-6.2 difference in specificity (%)
Interval -7.4 to -4.9
|
-5.0 difference in specificity (%)
Interval -6.3 to -3.8
|
-4.0 difference in specificity (%)
Interval -5.4 to -2.6
|
—
|
—
|
|
Specificity Difference in the Determination of Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Investigator
|
-1.5 difference in specificity (%)
Interval -2.1 to -0.9
|
-1.4 difference in specificity (%)
Interval -2.0 to -0.8
|
-2.1 difference in specificity (%)
Interval -2.8 to -1.3
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: For unifocal malignant disease, specificity analyses were based on a total number of 3307 regions (i.e. regions with no disease or multifocal malignant disease), 390 participants in FAS.
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for specificity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority reader response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=3307 Breast regions
|
CMRM
n=3307 Breast regions
|
CMRM vs CMRM+XRM
n=3307 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Majority read
|
-5.7 difference in specificity (%)
Interval -6.8 to -4.7
|
-4.3 difference in specificity (%)
Interval -5.3 to -3.3
|
-3.8 difference in specificity (%)
Interval -4.9 to -2.7
|
—
|
—
|
|
Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 1
|
-7.9 difference in specificity (%)
Interval -9.2 to -6.6
|
-6.0 difference in specificity (%)
Interval -7.3 to -4.8
|
-4.6 difference in specificity (%)
Interval -6.0 to -3.2
|
—
|
—
|
|
Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 2
|
-4.8 difference in specificity (%)
Interval -6.0 to -3.5
|
-2.5 difference in specificity (%)
Interval -3.7 to -1.3
|
-4.3 difference in specificity (%)
Interval -5.4 to -3.1
|
—
|
—
|
|
Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 3
|
-5.5 difference in specificity (%)
Interval -6.8 to -4.2
|
-4.4 difference in specificity (%)
Interval -5.7 to -3.2
|
-3.7 difference in specificity (%)
Interval -5.1 to -2.3
|
—
|
—
|
|
Specificity Difference in the Determination of Unifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Investigator
|
-1.0 difference in specificity (%)
Interval -1.6 to -0.4
|
-1.1 difference in specificity (%)
Interval -1.7 to -0.5
|
-1.3 difference in specificity (%)
Interval -2.0 to -0.7
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Single examinationPopulation: For multifocal malignant disease, specificity analyses were based on a total number of 3816 regions, 390 participants in FAS.
A malignant breast was defined as FP, when the reader using the respective imaging modality assessed more breast regions as malignant as were present according to SoT. Otherwise the breast was assessed as TN. Specificity was then defined as TN/(TN+FP). The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for specificity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority reader response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=3816 Breast regions
|
CMRM
n=3816 Breast regions
|
CMRM vs CMRM+XRM
n=3816 Breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Majority read
|
-1.8 difference in specificity (%)
Interval -2.9 to -0.6
|
-3.7 difference in specificity (%)
Interval -4.8 to -2.6
|
-1.8 difference in specificity (%)
Interval -3.0 to -0.6
|
—
|
—
|
|
Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 1
|
-2.0 difference in specificity (%)
Interval -3.3 to -0.6
|
-4.6 difference in specificity (%)
Interval -6.0 to -3.3
|
-2.0 difference in specificity (%)
Interval -3.4 to -0.5
|
—
|
—
|
|
Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 2
|
-3.8 difference in specificity (%)
Interval -5.1 to -2.6
|
-4.3 difference in specificity (%)
Interval -5.6 to -3.0
|
-5.6 difference in specificity (%)
Interval -6.9 to -4.4
|
—
|
—
|
|
Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Reader 3
|
-2.2 difference in specificity (%)
Interval -3.5 to -0.9
|
-2.7 difference in specificity (%)
Interval -4.0 to -1.4
|
-0.2 difference in specificity (%)
Interval -1.6 to 1.2
|
—
|
—
|
|
Specificity Difference in the Determination of Multifocal Malignant Breast Disease Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM, and CMRM+XRM vs XRM Verified by SoT, Breast Region Level
Investigator
|
0.2 difference in specificity (%)
Interval -0.7 to 1.0
|
-1.2 difference in specificity (%)
Interval -1.9 to -0.5
|
-1.4 difference in specificity (%)
Interval -2.2 to -0.6
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on a total number of 53 evaluable breasts with multicentric malignant disease.
For a single participant the sensitivity was defined as the proportion of malignant breast regions that were recognized by the reader using the respective imaging modality as malignant. Subsequently the sensitivity percentage was calculated based on the mean of the sensitivities across all participants. The majority read value for the 3 blinded readers was determined at the disease state level (evaluable regions for sensitivity). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave a different categorical determination, the majority response was the most severe disease category given by any of the 3 readers. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=53 evaluable breasts
|
CMRM
n=53 evaluable breasts
|
CMRM vs CMRM+XRM
n=53 evaluable breasts
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity Difference of Detection of Multicentric Malignant Disease Verified by SoT by Majority Reader, Breast Level
|
39.6 difference in sensitivity (%)
Interval 24.5 to 54.7
|
32.1 difference in sensitivity (%)
Interval 14.9 to 49.2
|
28.3 difference in sensitivity (%)
Interval 10.7 to 45.9
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 388 participants; evaluable subjects with at least one region verified by SoT in each breast with available CMRM, UMRM, CMRM+XRM, UMRM+XRM and XRM assessment.
The disease state "bilateral malignant disease" was derived from the assessment of the different regions for each breast (right and left) for investigators for each imaging modality (UMRM, CMRM, XRM, UMRM+XRM, and CMRM+XRM) based on the following rule: If the participant had at least one breast with no malignant region, the assessment of bilateral malignant disease was categorized as "No". If the participant had at least one malignant lesion in both breasts, the assessment of bilateral malignant disease was categorized as "Yes". The proportion of correct matches of each different image set to the SoT for the existence of bilateral malignant disease was derived. The analysis was based on the difference in accuracy for the evaluation of bilateral malignant disease for the following image comparisons on a participant level. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=388 Participants
|
CMRM
n=388 Participants
|
CMRM vs CMRM+XRM
n=388 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Majority Reader, Participant Level
|
-3.4 difference in accuracy (%)
Interval -6.1 to -0.7
|
-3.4 difference in accuracy (%)
Interval -6.1 to -0.6
|
-0.8 difference in accuracy (%)
Interval -3.8 to 2.2
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments by the majority reader for both modalities in the comparison for this assessment. Majority reader results are based on the average of the 3 blinded readers's assessment.
The 3 blinded readers each recorded his/her confidence in diagnosis for each breast region based on a 4-point scale (1=not confident, 2=somewhat confident, 3=confident, and 4=very confident). The majority read value for the 3 readers was determined at the disease state level (no disease, unifocal, multifocal). If 2 of 3 or all 3 readers gave the same categorical determination of malignant disease for a breast region, the majority reader response was that category. If all 3 readers gave different categorical determination, the majority reader response was the most severe disease category given by any of the 3 readers, i.e. multifocal. For each participant, the mean of the confidence responses for the diagnosed breast regions was calculated, and rounded to the nearest 0.5. value respectively. The difference was calculated as CMRM value minus UMRM value, CMRM+XRM value minus UMRM+XRM value, CMRM+XRM value minus XRM value respectively.
Outcome measures
| Measure |
CMRM vs UMRM
n=3890 breast regions
|
CMRM
n=3890 breast regions
|
CMRM vs CMRM+XRM
n=3893 breast regions
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Majority Reader, Participant Level
|
1.42 difference of scores on a scale
Interval 1.37 to 1.46
|
0.83 difference of scores on a scale
Interval 0.78 to 0.88
|
0.32 difference of scores on a scale
Interval 0.28 to 0.36
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure.
Inter-reader agreement was assessed by considering each breast region to have 2 possibilities (malignant disease / no malignant disease) for an assessment by the 2 image sets (UMRM and CMRM). Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Outcome measures
| Measure |
CMRM vs UMRM
n=3883 breast regions
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Readers: Inter-reader Agreement on Categorical Accuracy Based on Assessment for UMRM vs CMRM - Breast Region Level
|
0.48 kappa
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure.
Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Outcome measures
| Measure |
CMRM vs UMRM
n=775 evaluable breasts
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level
|
0.19 Kappa
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Outcome measures
| Measure |
CMRM vs UMRM
n=775 evaluable breasts
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level
|
0.21 Kappa
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure.
Intra-reader variability was assessed using a kappa on the match to SoT for the different regions within each participant (match, no match SoT). For each of the 3 readers, intra-reader agreement was assessed by considering each breast region to have 2 possibilities for an assessment by CMRM: matched SoT or did not match SoT. Kappa value varies from 0 (no agreement) to 1 (perfect agreement).
Outcome measures
| Measure |
CMRM vs UMRM
n=774 evaluable breasts
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level
|
0.26 Kappa
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Follow-up visit (24 hours post injection)Population: Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.
Systolic and diastolic blood pressure were measured in a supine position. Blood pressure was not to be measured on the arm used for the injection.
Outcome measures
| Measure |
CMRM vs UMRM
n=417 Participants
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure
Systolic blood pressure
|
-3.4 mmHg
Standard Deviation 13.7
|
—
|
—
|
—
|
—
|
|
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure
Diastolic blood pressure
|
-1.4 mmHg
Standard Deviation 9.9
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Follow-up visit (24 hours post injection)Population: Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.
Heart rate was measured in a supine position.
Outcome measures
| Measure |
CMRM vs UMRM
n=417 Participants
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate
|
-2.8 beats/min
Standard Deviation 9.5
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, Follow-up visit (24 hours post injection)Population: Safety Analysis Set (SAF): The analysis of safety data was performed using all available data from all participants who administered any amount of gadobutrol.
Number of participants with at least one occurrence of changing from low or normal at baseline to high at follow-up.
Outcome measures
| Measure |
CMRM vs UMRM
n=426 Participants
|
CMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection
Hematology
|
33 participants
|
—
|
—
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—
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—
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Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection
Clinical chemistry
|
100 participants
|
—
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—
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—
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—
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Number of Participants With at Least One Laboratory Parameter Change From Low or Normal at Baseline to Abnormally High at Follow-up 24 Hours Post Injection
Urinalysis
|
157 participants
|
—
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—
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—
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—
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Adverse Events
Gadobutrol (Gadavist, BAY 86-4875)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gadobutrol (Gadavist, BAY 86-4875)
n=426 participants at risk
Participants first received an unenhanced magnetic resonance mammography (MRM), followed by a gadobutrol-enhanced MRM. Gadobutrol was administered at the standard dose of 0.1 mmol/kg body weight (bw) \[0.1 ml/kg bw\] as an intravenous injection at a rate of 2 ml/sec. Unenhanced MRM (UMRM) and combined unenhanced and contrast (gadobutrol)-enhanced MRM (CMRM) image sets were evaluated in a randomized fashion. After the evaluation of the UMRM or CMRM the respective X-ray mammography (XRM) was added and evaluated together with the UMRM images.
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|---|---|
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Nervous system disorders
Dizziness
|
1.4%
6/426 • Adverse Events (AEs) that newly started between start of contrast injection and up to 24 hours post-contrast.
Treatment-Emergent AEs
|
|
Nervous system disorders
Headache
|
1.6%
7/426 • Adverse Events (AEs) that newly started between start of contrast injection and up to 24 hours post-contrast.
Treatment-Emergent AEs
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place