Risk of Nephrogenic Systemic Fibrosis (NSF) in Patients With Moderate Renal Insufficiency After the Administration of Magnevist

Renal Insufficiency Clinical Trial

Official title:

Prospective Non-randomized Observational (Pharmacoepidemiologic) Cohort Study (Open-label, Multicenter) to Assess the Magnitude of Potential Risk With the Administration of Magnevist® Injection in Patients With Moderate Renal Impairment for the Development of Nephrogenic Systemic Fibrosis (NSF) Based on Diagnostically Specific Clinical and Histopathologic Information.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00744939
• Other study ID #: 13256
• Secondary ID: X312141
• Status: Completed
• Phase: Phase 4
• First received: August 20, 2008
• Last updated: September 17, 2014
• Start date: November 2008
• Est. completion date: November 2013

Study information

• Verified date: September 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Observational

Clinical Trial Summary

Assess potential risk for NSF in subjects with renal impairment (moderate) post magnevist injection. Subjects will be screened within 48 hours of previously scheduled MRI, those meeting the enrollment criteria will be enrolled prior to MRI and followed for 2 years post MRI with visits occuring at 1yr and 2 yr timepoints, in addition follow-up phone calls conducted at 1, 3, 6 and 18 months to assess for skin changes suggestive of NSF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 168
• Est. completion date: November 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

Inclusion Criteria:

• Patients must have moderate (eGFR 30-59 ml/min/1.73 m^2) renal impairment and be scheduled for a contrast enhanced MRI with Magnevist Injection at the recommended dose of 0.1 mmol/kg.

Exclusion Criteria:

• Gadolinium Based Contrast Agent (other then Magnevist) enhanced MRI within 12 months prior to administration of Magnevist

• History of NSF

• Clinically unstable or age <2 yrs

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Fibrosis
• Kidney Failure
• Nephrogenic Fibrosing Dermopathy
• Renal Insufficiency

Intervention

Drug:
• Gadopentetate dimeglumine (Magnevist, BAY86-4882)
Patients will be followed for 2 years after the administration of Magnevist at the approved dose to see if symptoms consistent with NSF develop

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Developed Nephrogenic Systemic Fibrosis (NSF), Based on Diagnostically Specific Clinical and Histopathological Information-cohort Analysis and 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.	Up to 24 months following the administration of Magnevist	Yes
Primary	Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-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.	Up to 24 months following the administration of Magnevist	Yes
Primary	Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-cohort Analysis and Per Protocol 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.	Up to 24 months following the administration of Magnevist	Yes
Primary	Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-per Protocol 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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	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	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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	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	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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	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	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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	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	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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and 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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-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.	Up to 24 months following the administration of Magnevist	Yes
Secondary	Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Per Protocol Set	Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.	Up to 24 months following the administration of Magnevist	Yes
Secondary	Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-per Protocol Set	Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.	Up to 24 months following the administration of Magnevist	Yes

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