Trial Outcomes & Findings for Risk of Nephrogenic Systemic Fibrosis (NSF) in Patients With Moderate Renal Insufficiency After the Administration of Magnevist (NCT NCT00744939)
NCT ID: NCT00744939
Last Updated: 2014-09-22
Results Overview
Either clinical or histopathology score had to be at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 was derived from more than one minor criterion finding, one major criterion finding or more than one major criterion finding respectively. Major Criteria include patterned plaques, joint contractures, cobblestoning and marked induration/Peau d'orange (upper extremity or above knee); minor Criteria include puckering/linear banding, superficial (plaque/patch), dermal papules and scleral plaques (subject aged \<45 years). Pathology score 2, 3 or 4 was derived from 2, 3 or at least 4 histological criteria findings respectively. Histological Criteria include increased cellularity (spindled and/or epithelioid) with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of both fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and septal involvement.
COMPLETED
168 participants
Up to 24 months following the administration of Magnevist
2014-09-22
Participant Flow
The first participant's first visit was on 21 Nov 2008. Nineteen study centers in the United States screened and enrolled participants scheduled to undergo contrast enhanced magnetic resonance imaging (CE-MRI) with Magnevist within the approved indications at the recommended dose of 0.1 mmol/kg body weight.
A total of 168 participants were enrolled.
Participant milestones
| Measure |
Gadopentetate Dimeglumine (Magnevist, BAY86-4882)
Participants received Magnevist in accordance with its labeling.
|
|---|---|
|
Overall Study
STARTED
|
168
|
|
Overall Study
Treatment Received
|
141
|
|
Overall Study
COMPLETED
|
77
|
|
Overall Study
NOT COMPLETED
|
91
|
Reasons for withdrawal
| Measure |
Gadopentetate Dimeglumine (Magnevist, BAY86-4882)
Participants received Magnevist in accordance with its labeling.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
9
|
|
Overall Study
Protocol Violation
|
13
|
|
Overall Study
Death
|
24
|
|
Overall Study
distance
|
4
|
|
Overall Study
Lost to Follow-up
|
12
|
|
Overall Study
Medical history exclusionary
|
1
|
|
Overall Study
Did not receive Magnevist
|
7
|
|
Overall Study
Failed inclusion/exclusion criteria
|
19
|
|
Overall Study
coma
|
1
|
|
Overall Study
incorrect race
|
1
|
Baseline Characteristics
Risk of Nephrogenic Systemic Fibrosis (NSF) in Patients With Moderate Renal Insufficiency After the Administration of Magnevist
Baseline characteristics by cohort
| Measure |
Mild Renal Impairment
n=14 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
n=9 Participants
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=109 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=9 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
Total
n=141 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
65.0 Years
STANDARD_DEVIATION 12.03 • n=5 Participants
|
66.9 Years
STANDARD_DEVIATION 9.91 • n=7 Participants
|
66.4 Years
STANDARD_DEVIATION 12.09 • n=5 Participants
|
62.4 Years
STANDARD_DEVIATION 9.51 • n=4 Participants
|
66.0 Years
STANDARD_DEVIATION 11.75 • n=21 Participants
|
|
Age, Customized
<65 years
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
47 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
63 Participants
n=21 Participants
|
|
Age, Customized
>=65 years
|
9 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
62 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
79 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
102 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
132 Participants
n=21 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
21 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
81 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
109 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
|
Weight
|
85.2 Kilograms
STANDARD_DEVIATION 13.1 • n=5 Participants
|
81.9 Kilograms
STANDARD_DEVIATION 13.3 • n=7 Participants
|
86.0 Kilograms
STANDARD_DEVIATION 18.3 • n=5 Participants
|
83.2 Kilograms
STANDARD_DEVIATION 18.4 • n=4 Participants
|
85.5 Kilograms
STANDARD_DEVIATION 17.5 • n=21 Participants
|
|
Years since renal diagnosis
|
4.4 Years
STANDARD_DEVIATION 4.5 • n=5 Participants
|
0 Years
STANDARD_DEVIATION 0 • n=7 Participants
|
2.2 Years
STANDARD_DEVIATION 3.2 • n=5 Participants
|
3.1 Years
STANDARD_DEVIATION 4.6 • n=4 Participants
|
2.4 Years
STANDARD_DEVIATION 3.4 • n=21 Participants
|
|
Cause of renal disease
Diabetes
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
38 Participants
n=21 Participants
|
|
Cause of renal disease
Glomerulonephritis
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
|
Cause of renal disease
Collagen disease
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Cause of renal disease
Hypertension
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
53 Participants
n=21 Participants
|
|
Cause of renal disease
Polycystic kidney disease
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
|
Cause of renal disease
Other
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
68 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
84 Participants
n=21 Participants
|
|
Receiving dialysis
Any
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Receiving dialysis
Peritoneal dialysis
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Receiving dialysis
Hemodialysis
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
|
Vascular injuries
Any
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
43 Participants
n=21 Participants
|
|
Vascular injuries
Shunt surgery/repair
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Vascular injuries
Organ transplant surgery
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Vascular injuries
Thrombotic events
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
26 Participants
n=21 Participants
|
|
Vascular injuries
Other surgeries
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
15 Participants
n=21 Participants
|
|
Vascular injuries
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
|
MRI region of main interest
Brain
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
36 Participants
n=21 Participants
|
|
MRI region of main interest
Spine
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
|
MRI region of main interest
Liver
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
MRI region of main interest
Kidney
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
20 Participants
n=21 Participants
|
|
MRI region of main interest
Musculoskeletal
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
|
MRI region of main interest
Other
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
39 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Full Analysis Set
Either clinical or histopathology score had to be at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 was derived from more than one minor criterion finding, one major criterion finding or more than one major criterion finding respectively. Major Criteria include patterned plaques, joint contractures, cobblestoning and marked induration/Peau d'orange (upper extremity or above knee); minor Criteria include puckering/linear banding, superficial (plaque/patch), dermal papules and scleral plaques (subject aged \<45 years). Pathology score 2, 3 or 4 was derived from 2, 3 or at least 4 histological criteria findings respectively. Histological Criteria include increased cellularity (spindled and/or epithelioid) with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of both fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and septal involvement.
Outcome measures
| Measure |
Mild Renal Impairment
n=14 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
n=9 Participants
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=109 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=9 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants Who Developed Nephrogenic Systemic Fibrosis (NSF), Based on Diagnostically Specific Clinical and Histopathological Information-cohort Analysis and Full Analysis Set
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Full Analysis Set
Either clinical or histopathology score had to be at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 was derived from more than one minor criterion finding, one major criterion finding or more than one major criterion finding respectively. Major Criteria include patterned plaques, joint contractures, cobblestoning and marked induration/Peau d'orange (upper extremity or above knee); minor Criteria include puckering/linear banding, superficial (plaque/patch), dermal papules and scleral plaques (subject aged \<45 years). Pathology score 2, 3 or 4 was derived from 2, 3 or at least 4 histological criteria findings respectively. Histological Criteria include increased cellularity (spindled and/or epithelioid) with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of both fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and septal involvement.
Outcome measures
| Measure |
Mild Renal Impairment
n=141 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-full Analysis Set
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Per Protocol Set. Participants with mild and extended moderate renal impairment were excluded from the per protocol analysis.
Either clinical or histopathology score had to be at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 was derived from more than one minor criterion finding, one major criterion finding or more than one major criterion finding respectively. Major Criteria include patterned plaques, joint contractures, cobblestoning and marked induration/Peau d'orange (upper extremity or above knee); minor Criteria include puckering/linear banding, superficial (plaque/patch), dermal papules and scleral plaques (subject aged \<45 years). Pathology score 2, 3 or 4 was derived from 2, 3 or at least 4 histological criteria findings respectively. Histological Criteria include increased cellularity (spindled and/or epithelioid) with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of both fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and septal involvement.
Outcome measures
| Measure |
Mild Renal Impairment
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=58 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=8 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-cohort Analysis and Per Protocol Set
|
—
|
—
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Per Protocol Set. Participants with mild and extended moderate renal impairment were excluded from the per protocol analysis.
Either clinical or histopathology score had to be at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 was derived from more than one minor criterion finding, one major criterion finding or more than one major criterion finding respectively. Major Criteria include patterned plaques, joint contractures, cobblestoning and marked induration/Peau d'orange (upper extremity or above knee); minor Criteria include puckering/linear banding, superficial (plaque/patch), dermal papules and scleral plaques (subject aged \<45 years). Pathology score 2, 3 or 4 was derived from 2, 3 or at least 4 histological criteria findings respectively. Histological Criteria include increased cellularity (spindled and/or epithelioid) with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of both fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and septal involvement.
Outcome measures
| Measure |
Mild Renal Impairment
n=66 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-per Protocol Set
|
0 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Full analysis set
Either clinical or histopathology score need at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 required more than 1 minor criterion, 1 major criterion or more than 1 major criterion respectively. Major criteria: patterned plaques, joint contractures, cobblestoning, marked induration/Peau d'orange (upper extremity or above knee); minor Criteria: puckering/linear banding, superficial (plaque/patch), dermal papules, scleral plaques (subject aged \<45 yrs). Pathology score 2, 3 or 4 required 2, 3 or at least 4 histological criteria respectively. Histological criteria include Increased cellularity with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and Septal involvement. A clinical score of 4 was suggestive of developing clinical signs consistent with NSF in subjects without biopsy.
Outcome measures
| Measure |
Mild Renal Impairment
n=14 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
n=9 Participants
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=109 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=9 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Total Number of Participants With Clinicopathological Correlation of 'NSF' or 'Consistent With NSF' and Subjects Without Biopsy Developing Clinical Signs Consistent With NSF-cohort Analysis and Full Analysis Set
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Full analysis set
Either clinical or histopathology score need at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 required more than 1 minor criterion, 1 major criterion or more than 1 major criterion respectively. Major criteria: patterned plaques, joint contractures, cobblestoning, marked induration/Peau d'orange (upper extremity or above knee); minor Criteria: puckering/linear banding, superficial (plaque/patch), dermal papules, scleral plaques (subject aged \<45 yrs). Pathology score 2, 3 or 4 required 2, 3 or at least 4 histological criteria respectively. Histological criteria include Increased cellularity with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and Septal involvement. A clinical score of 4 was suggestive of developing clinical signs consistent with NSF in subjects without biopsy.
Outcome measures
| Measure |
Mild Renal Impairment
n=141 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Total Number of Participants With Clinicopathological Correlation of 'NSF' or 'Consistent With NSF' and Subjects Without Biopsy Developing Clinical Signs Consistent With NSF-full Analysis Set
|
0 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Per protocol set. Participants with mild and extended moderate renal impairment were excluded from the per protocol analysis.
Either clinical or histopathology score need at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 required more than 1 minor criterion, 1 major criterion or more than 1 major criterion respectively. Major criteria: patterned plaques, joint contractures, cobblestoning, marked induration/Peau d'orange (upper extremity or above knee); minor Criteria: puckering/linear banding, superficial (plaque/patch), dermal papules, scleral plaques (subject aged \<45 yrs). Pathology score 2, 3 or 4 required 2, 3 or at least 4 histological criteria respectively. Histological criteria include Increased cellularity with few other inflammatory cells, CD34+ spindle or epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and Septal involvement. A clinical score of 4 was suggestive of developing clinical signs consistent with NSF in subjects without biopsy.
Outcome measures
| Measure |
Mild Renal Impairment
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=58 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=8 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Total Number of Participants With Clinicopathological Correlation of 'NSF' or 'Consistent With NSF' and Subjects Without Biopsy Developing Clinical Signs Consistent With NSF-cohort Analysis and Per Protocol Set
|
—
|
—
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Per Protocol Set. Participants with mild and extended moderate renal impairment were excluded from the per protocol analysis.
Either clinical or histopathology score need at least 2 and the other at least 3 for diagnosis of NSF. Clinical score 2, 3 or 4 required more than 1 minor criterion, 1 major criterion or more than 1 major criterion respectively. Major criteria: patterned plaques, joint contractures, cobblestoning, marked induration/Peau d'orange (upper extremity or above knee); minor Criteria: puckering/linear banding, superficial (plaque/patch), dermal papules, scleral plaques (subject aged \<45 yrs). Pathology score 2, 3 or 4 required 2, 3 or at least 4 histological criteria respectively. Histological criteria include Increased cellularity with few other inflammatory cells, CD34+ spindle ore epithelioid cells in a reticular or parallel arrangement with "tram-tracking," presence of fine collagen and ropey collagen surrounded by clefts, elastic fibers preserved and Septal involvement. A clinical score of 4 was suggestive of developing clinical signs consistent with NSF in subjects without biopsy.
Outcome measures
| Measure |
Mild Renal Impairment
n=66 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Total Number of Participants With Clinicopathological Correlation of 'NSF' or 'Consistent With NSF' and Subjects Without Biopsy Developing Clinical Signs Consistent With NSF-per Protocol Set
|
0 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Full analysis set.
Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.
Outcome measures
| Measure |
Mild Renal Impairment
n=14 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
n=9 Participants
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=109 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=9 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Full Analysis Set
Participants with AEs within 1 day
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Full Analysis Set
Participants with skin-related AEs during FU
|
0 Participants
|
3 Participants
|
12 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Full analysis set
Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.
Outcome measures
| Measure |
Mild Renal Impairment
n=141 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-full Analysis Set
Participants with AEs within 1 day
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-full Analysis Set
Participants with skin-related AEs during FU
|
15 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Per protocol set. Participants with mild and extended moderate renal impairment were excluded from the per protocol analysis.
Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.
Outcome measures
| Measure |
Mild Renal Impairment
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=58 Participants
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=8 Participants
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Per Protocol Set
Participants with AEs within 1 day
|
—
|
—
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Per Protocol Set
Participants with skin related AEs during FU
|
—
|
—
|
7 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to 24 months following the administration of MagnevistPopulation: Per protocol set. Participants with mild and extended moderate renal impairment were excluded from the per protocol analysis.
Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.
Outcome measures
| Measure |
Mild Renal Impairment
n=66 Participants
Participants with estimated glomerular filtration rate (eGFR) \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-per Protocol Set
Participants with AEs within 1 day
|
0 Participants
|
—
|
—
|
—
|
|
Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-per Protocol Set
Participants with skin-related AEs during FU
|
7 Participants
|
—
|
—
|
—
|
Adverse Events
Mild Renal Impairment
Extended Moderate Renal Impairment
Moderate Renal Impairment
Severe Renal Impairment
Serious adverse events
| Measure |
Mild Renal Impairment
n=14 participants at risk
Participants with eGFR \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
n=9 participants at risk
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=109 participants at risk
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=9 participants at risk
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
Other adverse events
| Measure |
Mild Renal Impairment
n=14 participants at risk
Participants with eGFR \>65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of Mild renal impairment.
|
Extended Moderate Renal Impairment
n=9 participants at risk
Participants with eGFR between \>59 and ≤65 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of extended moderate renal impairment.
|
Moderate Renal Impairment
n=109 participants at risk
Participants with eGFR between ≥30 and ≤59 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of moderate renal impairment.
|
Severe Renal Impairment
n=9 participants at risk
Participants on dialysis or subjects with eGFR \<30 mL/min/1.73 m\^2 prior to Magnevist injection was classified into cohort of severe renal impairment.
|
|---|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
11.1%
1/9 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/109 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
11.1%
1/9 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/109 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
1.8%
2/109 • Number of events 2 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Dermatitis atopic
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 2 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
11.1%
1/9 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 2 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
3.7%
4/109 • Number of events 4 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
11.1%
1/9 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
1.8%
2/109 • Number of events 3 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
|
Skin and subcutaneous tissue disorders
Skin burning sensation
|
0.00%
0/14 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
0.92%
1/109 • Number of events 1 • Up to 24 months following the administration of Magnevist
|
0.00%
0/9 • Up to 24 months following the administration of Magnevist
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place