Long-Term Retention of Gadolinium in Bone

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Focus: Long-term Retention of Gadolinium-based Contrast Agent

Intervention / Treatment
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* Procedure: Gadolinium analysis in bone and tissue samples


Participation Criteria
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Eligibility Criteria
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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: 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 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 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gadolinium, Contrast Agent, Long-term retention