Long-Term Retention of Gadolinium in Bone

Exploratory Evaluation of the Potential for Long-term Retention of Gadolinium in the Bones of Patients Who Have Received Gadolinium Based Contrast Agents According to Their Medical History

The main objective was to prospectively explore the potential for long-term retention of Gadolinium (Gd) in bones in patients who have received a single dose of Gadolinium-based contrast agents (GBCA) or multiple doses of the same GBCA, with moderate or severe renal impairment or stable normal renal function (eGFR > 60 ml/min/1.73 m2) at the time of GBCA injection.

Study Overview

• Status: Completed
• Conditions: Focus: Long-term Retention of Gadolinium-based Contrast Agent
• Intervention / Treatment: Procedure: Gadolinium analysis in bone and tissue samples

Detailed Description

In order to collect additional clinical data this study was requested by the European Medicines Agency to further investigate whether Gd in human bone and skin are detectable for a long time after administration of GBCAs in patients with impaired renal function who had previously received any of the six different contrast agents (Gadobutrol, Gadodiamide, Gadopentetic acid, Gadoteric acid, Gadoversetamide, and Gadoxetic acid) within a magnetic resonance contrast imaging procedure and who are scheduled for an orthopaedic surgical procedure.

For this study the patients have not been administered any GBCA.

Participating sites are located in Germany, Italy, Poland, Spain, Turkey, USA, Japan, India and Republic of Korea.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Halle (Saale), Germany, 06097
    • University Hospital Halle (Saale)
  • Magdeburg, Germany, 39120
    • University Hospital Magdeburg
  • Würzburg, Germany, 97074
    • University Hospital Würzburg
• Japan
  • Fukuoka, Japan, 815-0063
    • Fukuoka Orthopaedic Hospital
  • Tokyo, Japan, 158-0095
    • Nissan Tamagawa Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 156-707
    • SMG-SNU Boramae Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center Orthopedic Surgery
• Spain
  • Alcorcón, Spain, 28922
    • Hospital Universitario Fundación Alcorcón
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Madrid, Spain, 28007
    • H.G.U. Gregorio Marañón
• Turkey
  • Istanbul, Turkey, 34010
    • Koc University Hospital, Orthopaedics and Traumatology Department
  • Istanbul, Turkey, 34303
    • Acibadem Hospital, Department of Orthopaedics and Traumatology
  • Istanbul, Turkey, 34752
    • Fatih Sultan Mehmet Training and Research Hospital, Department of Orthopedics and Traumatology
  • Istanbul, Turkey
    • Istanbul Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi
  • Izmir, Turkey, 35340
    • Dokuz Eylul University Tıp Faculty
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedar-Sinai Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Patient scheduled for an orthopaedic surgical procedure
• A minimum of 1 month has elapsed between GBCA dose and scheduled orthopaedic surgical procedure

• Patient belongs to one of the following subgroups with respect to the number of GBCA doses received and the status of their renal function:

  1. patient has stable impaired renal function (at least moderate impairment, eGFR ≤ 60 ml/min/1.73 m2) and has received one GBCA injection at the standard dose (0.025 mmol per kg body weight for Gadoxetic acid and 0.1 mmol per kg body weight for all other agents) or
  2. patient has stable impaired renal function (at least moderate impairment, eGFR ≤ 60 ml/min/1.73 m2) and has received more than one injection of the same GBCA or
  3. patient has stable normal renal function (eGFR > 60 ml/min /1.73 m2) and has received one GBCA injection at the standard dose (0.025 mmol per kg body weight for Gadoxetic acid and 0.1 mmol per kg body weight for all other agents) or
  4. patient has stable normal renal function (eGFR > 60 ml/min/1.73 m2) who have received more than one injection of the same GBCA

Main Exclusion Criteria:

• Patient has received different GBCAs.
• Patient has received intra-articular GBCA or per any other non-i.v. route
• Patient has received any investigational product or has participated in any other clinical trial within 30 days prior to enrolling in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: GBCA; Patients who have received GBCAs in the past	Procedure: Gadolinium analysis in bone and tissue samples; Gadolinium analysis in bone and tissue samples from patients undergoing an orthopaedic surgical procedure who had received GBCAs in the past.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Total Gadolinium in Trabecular Bone	Concentration of total Gd in trabecular bone determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Total Gadolinium in Cortical Bone	Concentration of total Gd in cortical bone determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of Total Gd in Skin Tissue Samples	Concentration of total Gd in skin tissue samples (determined by ICP-MS (inductively coupled plasma mass spectrometry)), collected at the time of the scheduled orthopaedic surgical procedure, from a biopsy from the edge of the surgical wound or the amputated part. Analysation of a single skin tissue sample; in case of a second surgery a further sample was taken.	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Calcium in Skin Tissue Samples	Concentration of calcium in skin tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Calcium in Cortical Bone Tissue Samples	Concentration of calcium in cortical bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Phosphorus in Cortical Bone Tissue Samples	Concentrations of phosphorus in cortical bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Sodium in Cortical Bone Tissue Samples	Concentrations of sodium in cortical bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Zinc in Bone Tissue Samples (Cortical)	Concentrations of zinc in cortical bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Potassium in Cortical Bone Tissue Samples	Concentration of potassium in bone (cortical) tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Iron in Cortical Bone Tissue Samples	Concentrations of iron in bone (cortical) tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Calcium in Trabecular Bone Tissue Samples	Concentrations of calcium in trabecular bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Phosphorus in Trabecular Bone Tissue Samples	Concentrations of phosphorus in bone (trabecular) tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Sodium in Trabecular Bone Tissue Samples	Concentrations of sodium in trabecular bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Zinc in Trabecular Bone Tissue Samples	Concentrations of zinc in trabecular bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Potassium in Trabecular Bone Tissue Samples	Concentrations of potassium in trabecular bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Iron in Trabecular Bone Tissue Samples	Concentrations of iron in trabecular bone tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Phosphorus in Skin Tissue Samples	Concentrations of phosphorus in skin tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Sodium in Skin Tissue Samples	Concentrations of sodium in skin tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Zinc in Skin Tissue Samples	Concentrations of zinc in skin tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Potassium in Skin Tissue Samples	Concentration of potassium in skin tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Iron in Skin Tissue Samples	Concentration of iron in skin tissue samples determined by ICP-MS	Day 0 (visit 2, surgery); optional visit 6 (second surgery)

Collaborators and Investigators

• Sponsor: Navitas Life Sciences GmbH
• Collaborators: GE Healthcare; Bayer; Guerbet
• Investigators: Principal Investigator: Christoph Lohmann, Professor MD, University Hospital Magdeburg, Germany

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2013
• Primary Completion (Actual): December 5, 2018
• Study Completion (Actual): December 17, 2018

Study Registration Dates

• First Submitted: May 10, 2013
• First Submitted That Met QC Criteria: May 10, 2013
• First Posted (Estimate): May 14, 2013

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Gadolinium; Contrast Agent; Long-term retention
• Other Study ID Numbers: ALS-Gd64/001

Plan for Individual participant data (IPD)

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