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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00744939
First received: August 20, 2008
Last updated: September 17, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Fibrosis
Kidney Failure
Renal Insufficiency
Drug: Gadopentetate dimeglumine (Magnevist, BAY86-4882)
Phase 4

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Number of Participants Who Developed Nephrogenic Systemic Fibrosis (NSF), Based on Diagnostically Specific Clinical and Histopathological Information-cohort Analysis and Full Analysis Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-full Analysis Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-cohort Analysis and Per Protocol Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants Who Developed NSF, Based on Diagnostically Specific Clinical and Histopathological Information-per Protocol Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • 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 [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    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.

  • Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Full Analysis Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.

  • Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-full Analysis Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.

  • Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-cohort Analysis and Per Protocol Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.

  • Number of Participants With Adverse Events (AEs) Reported in Association With the Administration of Magnevist-per Protocol Set [ Time Frame: Up to 24 months following the administration of Magnevist ] [ Designated as safety issue: Yes ]
    Adverse events occurring within 1 day after administration of Magnevist or skin-related adverse events occurring during follow-up (FU) were recorded.


Biospecimen Retention:   Samples Without DNA

Serum creatinine must be obtained within 6 weeks of the administration of Magnevist, or as currently recommended by the American College of Radiology. At the Baseline within 48 hrs. pre-injection a chemistry panel will be obtained in all patients after intravenous access has been obtained.


Enrollment: 168
Study Start Date: November 2008
Study Completion Date: November 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00744939

  Show 26 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00744939     History of Changes
Other Study ID Numbers: 13256, X312141
Study First Received: August 20, 2008
Results First Received: July 29, 2014
Last Updated: September 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Gadolinium
NSF
Renal Impairment
chemically induced
adverse effects
Contrast Media
complications

Additional relevant MeSH terms:
Fibrosis
Nephrogenic Fibrosing Dermopathy
Renal Insufficiency
Kidney Diseases
Pathologic Processes
Skin Diseases
Urologic Diseases
Gadobenic acid
Gadolinium DTPA
Contrast Media
Diagnostic Uses of Chemicals
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2014