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

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.

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.

Study Overview

• Status: Completed
• Conditions: Fibrosis; Renal Insufficiency; Kidney Failure
• Intervention / Treatment: Drug: Gadopentetate dimeglumine (Magnevist, BAY86-4882)

• Study Type: Observational
• Enrollment (Actual): 168

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85008
  • California
    • Chula Vista, California, United States, 91910
    • Los Angeles, California, United States, 90033
    • Santa Rosa, California, United States, 95405
  • Colorado
    • Pueblo, Colorado, United States, 81008
  • Connecticut
    • New Haven, Connecticut, United States, 06520--804
  • Florida
    • Jacksonville, Florida, United States, 32209-6595
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
    • Honolulu, Hawaii, United States, 96859
  • Kansas
    • Topeka, Kansas, United States, 66604
  • Maryland
    • Baltimore, Maryland, United States, 21287
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
    • Boston, Massachusetts, United States, 02114
    • Boston, Massachusetts, United States, 02118
  • New York
    • Brooklyn, New York, United States, 11219
    • New York, New York, United States, 10016
    • Stony Brook, New York, United States, 11790
  • Ohio
    • Cleveland, Ohio, United States, 44195
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822-2001
    • Philadelphia, Pennsylvania, United States, 19104
    • Philadelphia, Pennsylvania, United States, 19141
  • Tennessee
    • Memphis, Tennessee, United States, 38104
  • Texas
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78229
  • Virginia
    • Charlottesville, Virginia, United States, 22908
  • Washington
    • Tacoma, Washington, United States, 98321

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All patients who are scheduled to undergo CE-MRI with Magnevist and for which the inclusion and exclusion criteria are fulfilled are eligible for enrolment into the study.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gadopentetate dimeglumine (Magnevist, BAY86-4882); Participants received Magnevist in accordance with its labeling	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Bayer

Study record dates

Study Major Dates

• Study Start: November 1, 2008
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 20, 2008
• First Submitted That Met QC Criteria: August 29, 2008
• First Posted (Estimate): September 1, 2008

Study Record Updates

• Last Update Posted (Estimate): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 17, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: complications; Renal Impairment; Gadolinium; NSF; chemically induced; adverse effects; Contrast Media
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Kidney Diseases; Urologic Diseases; Fibrosis; Renal Insufficiency; Nephrogenic Fibrosing Dermopathy
• Other Study ID Numbers: 13256; X312141 (Other Identifier: Company internal)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No