Evaluation of Gd Retention in Human Bone and Skin After MultiHance or ProHance Administration Compared With Control

A Prospective Multicenter Cohort Study Evaluating the Long Term Retention of Gadolinium in Human Bone and Skin After the Retrospective Administration of MultiHance or ProHance in Comparison With a Control Group Receiving No Exposure to Gadolinium

Subjects must be scheduled to undergo an orthopedic surgical procedure. Subjects in the non-control group must have previously received an MRI with MultiHance or ProHance with at least 1 month between the last administration and the scheduled surgery. Subjects who have never received MultiHance or ProHance or any other gadolinium agent will also be enrolled. Subjects must have a test of their kidney function (SCr) at the time of the last MRI examination or at the time of enrollment if they never received gadolinium.

A sample of bone and skin will be collected from the scheduled surgery and tested for the amount of gadolinium. An additional sample of skin will be collected for testing the presence of nephrogenic systemic fibrosis (NSF).

Study Overview

• Status: Completed
• Conditions: Gadolinium Retention
• Intervention / Treatment: Procedure: Surgery

Detailed Description

Each subject enrolled will already be scheduled to undergo a hip, shoulder or knee replacement, limb amputations or other orthopedic surgical procedures and each subject enrolled in the non-control group will have retrospectively undergone one or more administrations of MultiHance or PROHANCE with the last dose administered at least 1 month before their scheduled surgery. In order to classify the subjects' renal status, the serum creatinine (SCr) value and/or estimated glomerular filtration rate (eGFR) at the time of last MRI with MultiHance or ProHance must be available and collected. The control subjects' documented SCr values will be collected prior to enrollment in the study.

The bone and skin tissue sample(s) collected (during the subjects surgery) will be blinded to gadolinium based contrast agent (GBCA) exposure and sent to a central laboratory where they will be tested for gadolinium (Gd) and other analytes including calcium, phosphorous, sodium, iron, zinc, and potassium. The Gd deposition of the resected bone and skin tissue will be analyzed by Inductively Coupled Plasma Mass Spectroscopy (ICP-MS). The bone and skin tissue will also be analyzed for other analytes using ICP-MS. These sample(s) will be stored at the central laboratory.

A separate sample of the skin tissue collected (during the subjects' surgery) will also be sent to a central dermatopathologist who will be blinded to GBCA exposure and test for any possible NSF related abnormalities. These skin tissue sample(s) will be stored with the central dermatopathology laboratory.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161
      • VA San Diego Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Subjects scheduled to have hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures

Description

Inclusion Criteria:

SUBJECTS WHO RECEIVED MULTIHANCE or PROHANCE:

• Is scheduled to receive hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
• Has undergone at least one MULTIHANCE or PROHANCE administration at least 1 month before his/her scheduled surgery
• Has a documented SCr for calculation of eGFR and/or documented eGFR at time of last MRI with MULTIHANCE or PROHANCE
• Provides written Informed Consent and is willing to comply with protocol requirements
• Is willing to undergo deep skin tissue sampling during scheduled hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
• Is ≥18 years of age

SUBJECTS WITH NO EXPOSURE TO GBCA:

• Is scheduled to receive hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
• Has no history of GBCA administration
• Provides written Informed Consent and is willing to comply with protocol requirements
• Is willing to undergo deep skin tissue sampling during scheduled hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
• Has prior SCr and/or eGFR at time of enrollment
• Is ≥18 years of age

Exclusion Criteria:

SUBJECTS WHO RECEIVED MULTI HANCE or PROHANCE:

• Has undergone any GBCA including MULTIHANCE or PROHANCE administration less than 1 month before his/her scheduled surgery
• Has ever been suspected of, or diagnosed with, NSF
• Has been suspected or diagnosed, prior to inclusion in this study, with bone cancer or any other osteoblastic or osteoclastic disease, such as septic, infectious or ischemic disease affecting physiological bone structure that has caused the bone to be diseased, prior to inclusion in this study
• Is unable or unwilling to be examined by dermatologists or to undergo laboratory/other diagnostic evaluations should development of NSF be suspected.
• Has received any GBCA other than the one under evaluation at any time prior to inclusion in this study (e.g., a MULTIHANCE subject should not receive any other GBCA including PROHANCE)

SUBJECTS WITH NO EXPOSURE TO GBCA:

• Has received any GBCA at any time prior to inclusion in this study
• Has ever been suspected of, or diagnosed with, NSF prior to the enrollment
• Has been suspected or diagnosed with bone cancer or any other osteoblastic or osteoclastic disease, such as septic, infectious or ischemic disease affecting physiological bone structure that has caused the bone to be diseased prior to inclusion in this study
• Is unable or unwilling to be examined by dermatologists or to undergo laboratory/other diagnostic evaluations should development of NSF be suspected.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
MultiHance Single Dose; Subjects who received a single dose of MultiHance and no other Gd agent and who are also scheduled for orthopedic surgery	Procedure: Surgery; hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
MultiHance Multiple Dose; Subjects who received multiple doses of MultiHance and no other Gd agent and who are also scheduled for orthopedic surgery	Procedure: Surgery; hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
ProHance Single Dose; Subjects who received a single dose of ProHance and no other Gd agent and who are also scheduled for orthopedic surgery	Procedure: Surgery; hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
ProHance Multiple Dose; Subjects who received multiple doses of ProHance and no other Gd agent and who are also scheduled for orthopedic surgery	Procedure: Surgery; hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures
Control Subgroup; Subjects who have not received any Gd agent and who are also scheduled for orthopedic surgery	Procedure: Surgery; hip, shoulder or knee replacement surgery, limb amputations or other orthopedic surgical procedures

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gadolinium deposition in bone and skin for non-control group	Determine the long-term gadolinium deposition in bone tissue and skin in subjects undergoing orthopedic surgery using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) in nmol gadolinium/g from surgically removed bone and skin.	At least one month from exposure to GBCA, assessed up to a total of 36 months
Gadolinium deposition in bone and skin for control group	Determine the long-term gadolinium deposition in bone tissue and skin in subjects undergoing orthopedic surgery using Inductively Coupled Plasma Mass Spectroscopy (ICP-MS) in nmol gadolinium/g from surgically removed bone and skin.	At any time, due to no GBCA exposure, assessed up to a total of 36 months

Collaborators and Investigators

• Sponsor: Bracco Diagnostics, Inc

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: February 22, 2017
• First Submitted That Met QC Criteria: April 5, 2017
• First Posted (Actual): April 11, 2017

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 13, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Skin; Bone; Gadolinium
• Other Study ID Numbers: GMRA-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No