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

NCT00744939 | Completed Results

• 2 other identifiers: 13256X312141
• Study Type: observational
• Target: 168
• Locations: 1 country
• Sites: 26

Brief 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.

Conditions

Fibrosis; Kidney Failure; Renal Insufficiency

Keywords

Gadolinium; NSF; Renal Impairment; chemically induced; adverse effects; Contrast Media; complications

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• 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

  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

  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

  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

  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

  Up to 24 months following the administration of Magnevist

Study Arms (1)

Gadopentetate dimeglumine (Magnevist, BAY86-4882)

Participants received Magnevist in accordance with its labeling

Drug: Gadopentetate dimeglumine (Magnevist, BAY86-4882)

Interventions

Gadopentetate dimeglumine (Magnevist, BAY86-4882) DRUG

Patients will be followed for 2 years after the administration of Magnevist at the approved dose to see if symptoms consistent with NSF develop

Gadopentetate dimeglumine (Magnevist, BAY86-4882)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (26)

Unknown Facility

Phoenix, Arizona, 85008, United States

Location

Unknown Facility

Chula Vista, California, 91910, United States

Location

Unknown Facility

Los Angeles, California, 90033, United States

Location

Unknown Facility

Santa Rosa, California, 95405, United States

Location

Unknown Facility

Pueblo, Colorado, 81008, United States

Location

Unknown Facility

New Haven, Connecticut, 06520--804, United States

Location

Unknown Facility

Jacksonville, Florida, 32209-6595, United States

Location

Unknown Facility

Honolulu, Hawaii, 96813, United States

Location

Unknown Facility

Honolulu, Hawaii, 96859, United States

Location

Unknown Facility

Topeka, Kansas, 66604, United States

Location

Unknown Facility

Baltimore, Maryland, 21287, United States

Location

Unknown Facility

Boston, Massachusetts, 02114, United States

Location

Unknown Facility

Boston, Massachusetts, 02118, United States

Location

Unknown Facility

Boston, Massachusetts, 02215, United States

Location

Unknown Facility

Brooklyn, New York, 11219, United States

Location

Unknown Facility

New York, New York, 10016, United States

Location

Unknown Facility

Stony Brook, New York, 11790, United States

Location

Unknown Facility

Cleveland, Ohio, 44195, United States

Location

Unknown Facility

Danville, Pennsylvania, 17822-2001, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19104, United States

Location

Unknown Facility

Philadelphia, Pennsylvania, 19141, United States

Location

Unknown Facility

Memphis, Tennessee, 38104, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Unknown Facility

San Antonio, Texas, 78229, United States

Location

Unknown Facility

Charlottesville, Virginia, 22908, United States

Location

Unknown Facility

Tacoma, Washington, 98321, United States

Location

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.

MeSH Terms

Conditions

Fibrosis; Renal Insufficiency

Interventions

Gadolinium DTPA

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pentetic Acid; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Coordination Complexes

Limitations and Caveats

Bayer HealthCare was informed about the release from the postmarketing surveillance (PMS) for Magnevist with a letter dated 02 JUN 2011. As a consequence Bayer HealthCare stopped enrollment for this study on 01 AUG 2011.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2008
• First Posted: September 1, 2008
• Study Start: November 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: November 1, 2013
• Last Updated: September 22, 2014
• Results First Posted: September 22, 2014

Record last verified: 2014-09

Locations

US (26)