Trial Outcomes & Findings for Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast Magnetic Resonance Imaging (MRI) (NCT NCT01104584)
NCT ID: NCT01104584
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
460 participants
Immediately before injection and after injection
2014-11-11
Participant Flow
Recruitment period: 16 May 2010 - 27 Sep 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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460
|
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Overall Study
Received Treatment
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439
|
|
Overall Study
Fulfilled Requirements of FAS Population
|
397
|
|
Overall Study
COMPLETED
|
437
|
|
Overall Study
NOT COMPLETED
|
23
|
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
|
21
|
|
Overall Study
Study prematurely discontinued
|
2
|
Baseline Characteristics
Efficacy and Safety of Gadobutrol 1.0 Molar (Gadovist) for Breast Magnetic Resonance Imaging (MRI)
Baseline characteristics by cohort
| Measure |
Gadobutrol (Gadavist, BAY86-4875)
n=439 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
|
57.1 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
438 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
310 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
104 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
17 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian/Alaska Native
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Missing
|
7 participants
n=5 Participants
|
|
Country
Argentina
|
19 participants
n=5 Participants
|
|
Country
Canada
|
33 participants
n=5 Participants
|
|
Country
Germany
|
91 participants
n=5 Participants
|
|
Country
Spain
|
66 participants
n=5 Participants
|
|
Country
India
|
63 participants
n=5 Participants
|
|
Country
Poland
|
70 participants
n=5 Participants
|
|
Country
Taiwan
|
36 participants
n=5 Participants
|
|
Country
United States
|
61 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 390 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 Versus UMRM
n=390 Participants
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 1
|
15.2 difference in sensitivity (%)
Interval 11.8 to 18.7
|
—
|
—
|
—
|
—
|
|
Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 2
|
31.9 difference in sensitivity (%)
Interval 27.3 to 36.6
|
—
|
—
|
—
|
—
|
|
Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 3
|
30.4 difference in sensitivity (%)
Interval 25.8 to 34.9
|
—
|
—
|
—
|
—
|
|
Difference of Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Investigator
|
15.9 difference in sensitivity (%)
Interval 12.4 to 19.4
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 390 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 Versus UMRM
n=390 Participants
|
UMRM
n=390 Participants
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 1
|
88.6 sensitivity (%)
Interval 86.1 to 91.1
|
73.3 sensitivity (%)
Interval 69.5 to 77.2
|
—
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 2
|
89.0 sensitivity (%)
Interval 86.4 to 91.6
|
57.0 sensitivity (%)
Interval 52.5 to 61.6
|
—
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Reader 3
|
85.5 sensitivity (%)
Interval 82.5 to 88.4
|
55.1 sensitivity (%)
Interval 50.5 to 59.8
|
—
|
—
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—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using CMRM vs UMRM Per Reader
Investigator
|
95.5 sensitivity (%)
Interval 93.9 to 97.1
|
79.5 sensitivity (%)
Interval 75.9 to 83.2
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 367 participants in FAS; evaluable for specificity were breasts without malignant disease as verified by Standard of Truth (SoT) for which a CMRM assessment was available.
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 Versus UMRM
n=367 Participants
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Reader 3
|
82.8 specificity (%)
Interval 79.0 to 86.7
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Investigator
|
95.4 specificity (%)
Interval 93.3 to 97.5
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Reader 1
|
91.8 specificity (%)
Interval 89.1 to 94.6
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM for Non-malignant Breasts by Reader
Reader 2
|
83.9 specificity (%)
Interval 80.2 to 87.7
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 390 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 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).
Outcome measures
| Measure |
CMRM Versus UMRM
n=390 Participants
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Breast Level Specificity of CMRM Based on Malignant Breasts
Reader 1
|
54.9 specificity (%)
Interval 49.9 to 59.8
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM Based on Malignant Breasts
Reader 2
|
47.2 specificity (%)
Interval 42.2 to 52.1
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM Based on Malignant Breasts
Reader 3
|
55.5 specificity (%)
Interval 50.6 to 60.4
|
—
|
—
|
—
|
—
|
|
Breast Level Specificity of CMRM Based on Malignant Breasts
Investigator
|
93.8 specificity (%)
Interval 91.5 to 96.2
|
—
|
—
|
—
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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; index cancer was defined as the cancer confirmed by histology prior to inclusion which made the participant eligible for the study.
Index cancer was 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 Versus UMRM
n=388 Participants
|
UMRM
n=388 Participants
|
CMRM vs CMRM+XRM
n=388 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 2
|
30.2 difference in percentage of participants
Interval 25.0 to 35.4
|
13.9 difference in percentage of participants
Interval 9.2 to 18.7
|
-1.3 difference in percentage of participants
Interval -3.2 to 0.6
|
—
|
—
|
|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 1
|
15.5 difference in percentage of participants
Interval 11.1 to 19.8
|
19.8 difference in percentage of participants
Interval 14.9 to 24.8
|
-1.0 difference in percentage of participants
Interval -2.9 to 0.8
|
—
|
—
|
|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 3
|
30.9 difference in percentage of participants
Interval 25.6 to 36.2
|
12.9 difference in percentage of participants
Interval 7.8 to 17.9
|
-2.6 difference in percentage of participants
Interval -4.6 to -0.6
|
—
|
—
|
|
Percentage Difference of Participants Whose Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Investigator
|
14.2 difference in percentage of participants
Interval 10.4 to 18.0
|
2.3 difference in percentage of participants
Interval 0.0 to 4.6
|
-0.5 difference in percentage of participants
Interval -1.8 to 0.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Immediately before injection and after injectionPopulation: The evaluation was based on the 84 participants in the 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 Versus UMRM
n=84 Participants
|
UMRM
n=84 Participants
|
CMRM vs CMRM+XRM
n=84 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 3
|
34.5 difference in percentage of participants
Interval 22.6 to 46.4
|
26.2 difference in percentage of participants
Interval 13.5 to 38.9
|
-2.4 difference in percentage of participants
Interval -6.8 to 2.1
|
—
|
—
|
|
Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 1
|
23.8 difference in percentage of participants
Interval 12.4 to 35.2
|
42.9 difference in percentage of participants
Interval 30.6 to 55.1
|
0.0 difference in percentage of participants
Interval -4.5 to 4.5
|
—
|
—
|
|
Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Reader 2
|
44.0 difference in percentage of participants
Interval 31.7 to 56.4
|
48.8 difference in percentage of participants
Interval 36.4 to 61.2
|
0.0 difference in percentage of participants
Interval -1.2 to 1.2
|
—
|
—
|
|
Percentage Difference of Participants Whose Additional Index Cancers Were Detected Using CMRM vs UMRM, CMRM vs XRM, and CMRM vs CMRM+XRM
Investigator
|
35.7 difference in percentage of participants
Interval 24.3 to 47.2
|
40.5 difference in percentage of participants
Interval 28.3 to 52.7
|
-1.2 difference in percentage of participants
Interval -4.7 to 2.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
The investigator and the 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). For each participant, the mean of the confidence responses for the diagnosed breast regions was calculated, and rounded to the nearest 0.5. 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 Versus UMRM
n=397 Participants
|
UMRM
n=397 Participants
|
CMRM vs CMRM+XRM
n=397 Participants
|
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 Reader, Participant Level
Reader 1
|
0.97 difference of scores on a scale
Interval 0.94 to 1.0
|
1.25 difference of scores on a scale
Interval 1.19 to 1.31
|
-0.23 difference of scores on a scale
Interval -0.28 to -0.19
|
—
|
—
|
|
Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level
Reader 2
|
0.95 difference of scores on a scale
Interval 0.91 to 0.99
|
0.74 difference of scores on a scale
Interval 0.69 to 0.79
|
0.04 difference of scores on a scale
Interval -0.01 to 0.09
|
—
|
—
|
|
Difference of Confidence in Diagnosis for Breast Region Diagnosis Using CMRM vs UMRM, CMRM+XRM vs UMRM+XRM and CMRM+XRM vs XRM by Reader, Participant Level
Reader 3
|
1.73 difference of scores on a scale
Interval 1.68 to 1.78
|
1.64 difference of scores on a scale
Interval 1.57 to 1.7
|
0.67 difference of scores on a scale
Interval 0.61 to 0.74
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were performed for a total number of 390 participants who had regions with malignant disease verified by SoT with available assessment by the imaging modality.
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.
Outcome measures
| Measure |
CMRM Versus UMRM
n=390 Participants
|
UMRM
n=390 Participants
|
CMRM vs CMRM+XRM
n=390 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader
Reader 1
|
69.6 sensitivity (%)
Interval 65.8 to 73.4
|
89.6 sensitivity (%)
Interval 87.3 to 92.0
|
82.5 sensitivity (%)
Interval 79.5 to 85.6
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader
Reader 2
|
72.9 sensitivity (%)
Interval 69.2 to 76.7
|
90.3 sensitivity (%)
Interval 87.9 to 92.7
|
80.9 sensitivity (%)
Interval 77.6 to 84.1
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader
Reader 3
|
73.2 sensitivity (%)
Interval 69.5 to 76.9
|
88.0 sensitivity (%)
Interval 85.3 to 90.6
|
80.1 sensitivity (%)
Interval 76.8 to 83.4
|
—
|
—
|
|
Sensitivity for Detection of Full Extent of Malignant Breast Disease Using XRM, CMRM+XRM and UMRM+XRM Per Reader
Investigator
|
89.1 sensitivity (%)
Interval 86.6 to 91.5
|
96.0 sensitivity (%)
Interval 94.6 to 97.5
|
92.1 sensitivity (%)
Interval 90.0 to 94.2
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 367 participants; evaluable for specificity were breasts with no malignant disease verified by SoT for which an assessment of the imaging modality was available.
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 Versus UMRM
n=367 Participants
|
UMRM
n=367 Participants
|
CMRM vs CMRM+XRM
n=367 Participants
|
UMRM+XRM
n=367 Participants
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Reader 1
|
94.4 specificity (%)
Interval 92.1 to 96.7
|
92.6 specificity (%)
Interval 90.0 to 95.3
|
92.2 specificity (%)
Interval 89.5 to 94.9
|
94.3 specificity (%)
Interval 92.0 to 96.6
|
—
|
|
Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Reader 2
|
96.6 specificity (%)
Interval 94.8 to 98.4
|
90.3 specificity (%)
Interval 87.3 to 93.3
|
83.1 specificity (%)
Interval 79.3 to 86.9
|
91.0 specificity (%)
Interval 88.1 to 93.9
|
—
|
|
Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Reader 3
|
95.9 specificity (%)
Interval 93.9 to 97.9
|
86.1 specificity (%)
Interval 82.6 to 89.6
|
83.0 specificity (%)
Interval 79.1 to 86.8
|
85.1 specificity (%)
Interval 81.5 to 88.8
|
—
|
|
Breast Level Specificity of in Non-malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Investigator
|
98.1 specificity (%)
Interval 96.8 to 98.4
|
97.8 specificity (%)
Interval 96.4 to 99.2
|
95.1 specificity (%)
Interval 92.9 to 97.2
|
97.5 specificity (%)
Interval 96.1 to 99.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 390 participants; 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 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).
Outcome measures
| Measure |
CMRM Versus UMRM
n=390 Participants
|
UMRM
n=390 Participants
|
CMRM vs CMRM+XRM
n=390 Participants
|
UMRM+XRM
n=390 Participants
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Reader 1
|
71.9 specificity (%)
Interval 67.5 to 76.4
|
86.8 specificity (%)
Interval 83.4 to 90.2
|
52.7 specificity (%)
Interval 47.8 to 57.6
|
69.1 specificity (%)
Interval 64.5 to 73.7
|
—
|
|
Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Reader 2
|
76.2 specificity (%)
Interval 71.9 to 80.4
|
75.8 specificity (%)
Interval 71.5 to 80.0
|
46.5 specificity (%)
Interval 41.6 to 51.5
|
65.4 specificity (%)
Interval 60.7 to 70.1
|
—
|
|
Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Reader 3
|
77.6 specificity (%)
Interval 73.4 to 81.7
|
69.4 specificity (%)
Interval 64.8 to 73.9
|
54.5 specificity (%)
Interval 49.6 to 59.4
|
66.9 specificity (%)
Interval 62.2 to 71.6
|
—
|
|
Breast Level Specificity in Malignant Breasts Using UMRM, XRM, CMRM+XRM and UMRM+XRM by Reader
Investigator
|
96.2 specificity (%)
Interval 94.2 to 98.1
|
97.7 specificity (%)
Interval 96.2 to 99.2
|
93.8 specificity (%)
Interval 91.5 to 96.2
|
96.0 specificity (%)
Interval 94.1 to 98.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 395 participants in FAS; evaluable for specificity were breasts with or without malignant disease verified by SoT with available assessments by the imaging modality.
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 Versus UMRM
n=395 Participants
|
UMRM
n=395 Participants
|
CMRM vs CMRM+XRM
n=395 Participants
|
UMRM+XRM
n=395 Participants
|
CMRM+XRM
n=395 Participants
|
|---|---|---|---|---|---|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Reader 2
|
86.1 specificity (%)
Interval 83.7 to 88.4
|
64.9 specificity (%)
Interval 61.9 to 68.0
|
83.0 specificity (%)
Interval 80.4 to 85.7
|
77.8 specificity (%)
Interval 75.1 to 80.6
|
64.3 specificity (%)
Interval 61.2 to 67.4
|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Investigator
|
96.6 specificity (%)
Interval 95.3 to 97.9
|
94.1 specificity (%)
Interval 92.4 to 95.8
|
97.1 specificity (%)
Interval 95.9 to 98.3
|
96.2 specificity (%)
Interval 94.9 to 97.6
|
94.0 specificity (%)
Interval 92.2 to 95.7
|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Reader 1
|
83.0 specificity (%)
Interval 80.6 to 85.5
|
73.0 specificity (%)
Interval 70.2 to 75.9
|
89.7 specificity (%)
Interval 87.7 to 91.7
|
81.3 specificity (%)
Interval 78.8 to 83.8
|
72.0 specificity (%)
Interval 69.2 to 74.8
|
|
Breast Level Specificity for All Breasts by Imaging Modality and by Reader
Reader 3
|
86.5 specificity (%)
Interval 84.1 to 88.8
|
68.6 specificity (%)
Interval 65.4 to 71.8
|
77.6 specificity (%)
Interval 74.8 to 80.3
|
75.9 specificity (%)
Interval 73.0 to 78.9
|
68.1 specificity (%)
Interval 64.9 to 71.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 point estimates were calculated based on the mean of the sensitivities across all participants. Regions with malignant disease verified by SoT comprise unifocal and multifocal regions. Difference in sensitivity is 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 Versus UMRM
n=630 breast regions
|
UMRM
n=630 breast regions
|
CMRM vs CMRM+XRM
n=630 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
Reader 1
|
17.5 difference in sensitivity (%)
Interval 14.2 to 20.8
|
9.5 difference in sensitivity (%)
Interval 1.9 to 17.1
|
24.3 difference in sensitivity (%)
Interval 20.7 to 27.9
|
—
|
—
|
|
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
|
34.9 difference in sensitivity (%)
Interval 30.1 to 39.7
|
12.5 difference in sensitivity (%)
Interval 9.4 to 15.6
|
21.3 difference in sensitivity (%)
Interval 17.6 to 24.9
|
—
|
—
|
|
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
|
32.1 difference in sensitivity (%)
Interval 27.2 to 36.9
|
10.0 difference in sensitivity (%)
Interval 6.9 to 13.1
|
16.5 difference in sensitivity (%)
Interval 13.0 to 20.0
|
—
|
—
|
|
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
|
19.0 difference in sensitivity (%)
Interval 14.8 to 23.3
|
6.7 difference in sensitivity (%)
Interval 3.7 to 9.6
|
10.5 difference in sensitivity (%)
Interval 5.7 to 15.2
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is 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 Versus UMRM
n=570 breast regions
|
UMRM
n=570 breast regions
|
CMRM vs CMRM+XRM
n=570 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
Reader 1
|
-5.8 difference in sensitivity (%)
Interval -11.1 to -0.4
|
-12.6 difference in sensitivity (%)
Interval -17.7 to -7.5
|
-10.2 difference in sensitivity (%)
Interval -15.3 to -5.1
|
—
|
—
|
|
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
|
12.0 difference in sensitivity (%)
Interval 7.7 to 16.2
|
0.2 difference in sensitivity (%)
Interval -2.8 to 3.1
|
2.3 difference in sensitivity (%)
Interval -1.4 to 6.0
|
—
|
—
|
|
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
|
4.6 difference in sensitivity (%)
Interval -1.3 to 10.4
|
-12.3 difference in sensitivity (%)
Interval -17.4 to -7.2
|
-12.0 difference in sensitivity (%)
Interval -17.6 to -6.3
|
—
|
—
|
|
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 3
|
19.5 difference in sensitivity (%)
Interval 14.2 to 24.8
|
-1.9 difference in sensitivity (%)
Interval -6.4 to 2.6
|
6.9 difference in sensitivity (%)
Interval 2.0 to 11.7
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 point estimates were calculated based on the mean of the sensitivities across all participants. The difference in sensitivity is 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 Versus UMRM
n=60 breast regions
|
UMRM
n=60 breast regions
|
CMRM vs CMRM+XRM
n=60 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
Reader 1
|
46.7 difference in sensitivity (%)
Interval 32.7 to 60.6
|
40.0 difference in sensitivity (%)
Interval 26.0 to 54.0
|
65.0 difference in sensitivity (%)
Interval 52.1 to 77.9
|
—
|
—
|
|
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
|
51.7 difference in sensitivity (%)
Interval 37.5 to 65.9
|
35.0 difference in sensitivity (%)
Interval 20.9 to 49.1
|
46.7 difference in sensitivity (%)
Interval 32.2 to 61.1
|
—
|
—
|
|
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 3
|
31.7 difference in sensitivity (%)
Interval 18.0 to 45.3
|
21.7 difference in sensitivity (%)
Interval 10.3 to 33.1
|
11.7 difference in sensitivity (%)
Interval -3.5 to 26.8
|
—
|
—
|
|
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
Investigator
|
25.4 difference in sensitivity (%)
Interval 14.3 to 36.5
|
21.7 difference in sensitivity (%)
Interval 11.2 to 32.1
|
36.7 difference in sensitivity (%)
Interval 23.2 to 50.1
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 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 Versus UMRM
n=3197 breast regions
|
UMRM
n=3197 breast regions
|
CMRM vs CMRM+XRM
n=3197 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
Reader 1
|
-4.1 difference in specificity (%)
Interval -5.3 to -2.9
|
-3.9 difference in specificity (%)
Interval -5.1 to -2.8
|
-6.7 difference in specificity (%)
Interval -8.0 to -5.4
|
—
|
—
|
|
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
|
-8.4 difference in specificity (%)
Interval -9.9 to -7.0
|
-5.7 difference in specificity (%)
Interval -7.2 to -4.2
|
-7.5 difference in specificity (%)
Interval -9.0 to -6.0
|
—
|
—
|
|
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
|
-6.1 difference in specificity (%)
Interval -7.6 to -4.7
|
-2.0 difference in specificity (%)
Interval -3.5 to -0.5
|
-3.2 difference in specificity (%)
Interval -4.7 to -1.6
|
—
|
—
|
|
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
|
-1.0 difference in specificity (%)
Interval -1.6 to -0.5
|
-0.9 difference in specificity (%)
Interval -1.5 to -0.4
|
-1.3 difference in specificity (%)
Interval -1.9 to -0.8
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 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 Versus UMRM
n=3257 breast regions
|
UMRM
n=3257 breast regions
|
CMRM vs CMRM+XRM
n=3257 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
Reader 1
|
-3.2 difference in specificity (%)
Interval -4.5 to -1.9
|
-3.1 difference in specificity (%)
Interval -4.3 to -1.9
|
-5.6 difference in specificity (%)
Interval -7.0 to -4.3
|
—
|
—
|
|
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
Reader 2
|
-7.3 difference in specificity (%)
Interval -8.8 to -5.8
|
-5.0 difference in specificity (%)
Interval -6.5 to -3.5
|
-6.6 difference in specificity (%)
Interval -8.1 to -5.0
|
—
|
—
|
|
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
|
-5.4 difference in specificity (%)
Interval -6.9 to -4.0
|
-1.6 difference in specificity (%)
Interval -3.1 to -0.1
|
-3.1 difference in specificity (%)
Interval -4.7 to -1.6
|
—
|
—
|
|
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
|
-0.4 difference in specificity (%)
Interval -0.9 to 0.1
|
-0.4 difference in specificity (%)
Interval -0.9 to 0.1
|
-0.5 difference in specificity (%)
Interval -1.1 to 0.1
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 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 Versus UMRM
n=3767 breast regions
|
UMRM
n=3767 breast regions
|
CMRM vs CMRM+XRM
n=3767 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
Reader 1
|
-4.4 difference in specificity (%)
Interval -5.7 to -3.0
|
-5.3 difference in specificity (%)
Interval -6.5 to -4.0
|
-7.5 difference in specificity (%)
Interval -8.8 to -6.1
|
—
|
—
|
|
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
|
-6.5 difference in specificity (%)
Interval -8.0 to -5.0
|
-6.7 difference in specificity (%)
Interval -8.2 to -5.2
|
-8.2 difference in specificity (%)
Interval -9.8 to -6.7
|
—
|
—
|
|
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
|
-2.3 difference in specificity (%)
Interval -3.8 to -0.8
|
-2.0 difference in specificity (%)
Interval -3.5 to -0.5
|
-1.9 difference in specificity (%)
Interval -3.4 to -0.3
|
—
|
—
|
|
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
|
1.1 difference in specificity (%)
Interval 0.3 to 1.9
|
-0.7 difference in specificity (%)
Interval -1.4 to 0.0
|
-0.7 difference in specificity (%)
Interval -1.5 to 0.1
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: All participants in the FAS with assessments for this outcome measure
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 point estimates were calculated based on the mean of the sensitivities across all participants. 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 Versus UMRM
n=44 evaluable breasts
|
UMRM
n=44 evaluable breasts
|
CMRM vs CMRM+XRM
n=44 evaluable breasts
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level
Reader 1
|
47.7 difference in sensitivity (%)
Interval 31.7 to 63.8
|
38.6 difference in sensitivity (%)
Interval 22.9 to 54.3
|
75.0 difference in sensitivity (%)
Interval 62.2 to 87.8
|
—
|
—
|
|
Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level
Reader 2
|
56.8 difference in sensitivity (%)
Interval 40.9 to 72.8
|
40.9 difference in sensitivity (%)
Interval 23.9 to 58.0
|
61.4 difference in sensitivity (%)
Interval 45.7 to 77.1
|
—
|
—
|
|
Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level
Reader 3
|
47.7 difference in sensitivity (%)
Interval 31.7 to 63.8
|
31.8 difference in sensitivity (%)
Interval 18.1 to 45.6
|
43.2 difference in sensitivity (%)
Interval 27.2 to 59.1
|
—
|
—
|
|
Sensitivity of Detection of Multicentric Malignant Disease Verified by SoT, Breast Level
Investigator
|
34.1 difference in sensitivity (%)
Interval 18.7 to 49.4
|
31.8 difference in sensitivity (%)
Interval 16.7 to 47.0
|
52.3 difference in sensitivity (%)
Interval 37.5 to 67.0
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The analyses were based on 380 participants in FAS; 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 were 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 Versus UMRM
n=380 Participants
|
UMRM
n=380 Participants
|
CMRM vs CMRM+XRM
n=380 Participants
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Accuracy Difference of Presence of Bilateral Malignant Disease Verified by SoT by Clinical Investigator, Participant Level
|
0.5 difference in accuracy (%)
Interval -2.0 to 3.1
|
-0.3 difference in accuracy (%)
Interval -2.5 to 2.0
|
-0.8 difference in accuracy (%)
Interval -3.2 to 1.6
|
—
|
—
|
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 Versus UMRM
n=3827 breast regions
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Readers: Inter-reader Agreement on Sensitivity Based on Assessment for UMRM vs CMRM - Breast Region Level
|
0.47 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 Versus UMRM
n=756 evaluable breasts
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Reader 1: Intra-reader Variability Based on Assessment for CMRM - Breast Level
|
0.25 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 Versus UMRM
n=756 evaluable breasts
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Reader 2: Intra-reader Variability Based on Assessment for CMRM - Breast Level
|
0.23 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 Versus UMRM
n=756 evaluable breasts
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Blinded Reader 3: Intra-reader Variability Based on Assessment for CMRM - Breast Level
|
0.21 Kappa
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The Statistical Analysis Plan (SAP) amendment re-defined study objectives and replaced protocol-defined parameters such as categorical accuracy prior to database closure and breaking the blind. The SAP amendment is based upon review of results of an identical clinical study within the "GEMMA" program and also includes advice from the FDA.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Immediately before injection and after injectionPopulation: The Statistical Analysis Plan (SAP) amendment re-defined study objectives and replaced protocol-defined parameters such as categorical accuracy prior to database closure and breaking the blind. The SAP amendment is based upon review of results of an identical clinical study within the "GEMMA" program and also includes advice from the FDA.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline, 24 hours post injectionPopulation: 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 Versus UMRM
n=432 Participants
|
UMRM
|
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
|
-2.7 mmHg
Standard Deviation 15.2
|
—
|
—
|
—
|
—
|
|
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Systolic and Diastolic Blood Pressure
Diastolic blood pressure
|
-2.3 mmHg
Standard Deviation 9.7
|
—
|
—
|
—
|
—
|
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 Versus UMRM
n=431 Participants
|
UMRM
|
CMRM vs CMRM+XRM
|
UMRM+XRM
|
CMRM+XRM
|
|---|---|---|---|---|---|
|
Vital Signs Change From Baseline and Follow-up 24 Hours Post Injection - Heart Rate
|
-1.7 beats/min
Standard Deviation 10.1
|
—
|
—
|
—
|
—
|
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 Versus UMRM
n=439 Participants
|
UMRM
|
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
|
41 Participants
|
—
|
—
|
—
|
—
|
|
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
|
107 Participants
|
—
|
—
|
—
|
—
|
|
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
|
144 Participants
|
—
|
—
|
—
|
—
|
Adverse Events
Gadobutrol (Gadavist, BAY86-4875)
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Gadobutrol (Gadavist, BAY86-4875)
n=439 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.
|
|---|---|
|
Nervous system disorders
Headache
|
1.4%
6/439 • Between start of contrast injection and up to 24 hours post-contrast
Treatment-emergent Adverse Events (AEs)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place