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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01853163

Enrollment

Registered

2013-05-14

Start date

2013-05-06

Completion date

2018-12-17

Last updated

2022-09-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

Keywords

Gadolinium, Contrast Agent, Long-term retention

Brief summary

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

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.

Interventions

PROCEDUREGadolinium 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

SCREENING

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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.

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Concentration of Calcium in Cortical Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentration of calcium in cortical bone tissue samples determined by ICP-MS
Concentrations of Phosphorus in Cortical Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of phosphorus in cortical bone tissue samples determined by ICP-MS
Concentrations of Sodium in Cortical Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of sodium in cortical bone tissue samples determined by ICP-MS
Concentrations of Zinc in Bone Tissue Samples (Cortical)	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of zinc in cortical bone tissue samples determined by ICP-MS
Concentration of Potassium in Cortical Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentration of potassium in bone (cortical) tissue samples determined by ICP-MS
Concentrations of Iron in Cortical Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of iron in bone (cortical) tissue samples determined by ICP-MS
Concentration of Calcium in Trabecular Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of calcium in trabecular bone tissue samples determined by ICP-MS
Concentration of Phosphorus in Trabecular Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of phosphorus in bone (trabecular) tissue samples determined by ICP-MS
Concentration of Total Gd in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	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.
Concentrations of Zinc in Trabecular Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of zinc in trabecular bone tissue samples determined by ICP-MS
Concentrations of Potassium in Trabecular Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of potassium in trabecular bone tissue samples determined by ICP-MS
Concentrations of Iron in Trabecular Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of iron in trabecular bone tissue samples determined by ICP-MS
Concentrations of Phosphorus in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of phosphorus in skin tissue samples determined by ICP-MS
Concentrations of Sodium in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of sodium in skin tissue samples determined by ICP-MS
Concentrations of Zinc in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of zinc in skin tissue samples determined by ICP-MS
Concentration of Potassium in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentration of potassium in skin tissue samples determined by ICP-MS
Concentration of Iron in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentration of iron in skin tissue samples determined by ICP-MS
Concentrations of Sodium in Trabecular Bone Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentrations of sodium in trabecular bone tissue samples determined by ICP-MS
Concentration of Calcium in Skin Tissue Samples	Day 0 (visit 2, surgery); optional visit 6 (second surgery)	Concentration of calcium in skin tissue samples determined by ICP-MS

Countries

Germany, Japan, South Korea, Spain, Turkey (Türkiye), United States

Participant flow

Pre-assignment details

Study sample size was decreased on the basis of protocol amendment #2 date 26 FEB 2016.

Participants by arm

Arm	Count
GBCA Exposure Group - Normal Renal Function. Patients with normal renal function (eGFR \> 60 ml/min /1.73 m2) who received at least one months prior to the scheduled orthopaedic surgical procedure one or multiple injections of the same GBCA.	45
GBCA Exposure Group - Impaired Renal Function. Patients with impaired renal function (eGFR ≤ 60 ml/min/1.73 m2) who received at least one months prior to the scheduled orthopaedic surgical procedure one or multiple injections of the same GBCA.	29
GBCA Naive - Control Group With Normal Renal Function. GBCA naive patients with normal renal function (eGFR \> 60 ml/min/1.73 m2)	7
GBCA Naive - Control Group With Impaired Renal Function. GBCA naive patients with impaired renal function (eGFR ≤ 60 ml/min/1.73 m2)	11
Total	92

Baseline characteristics

Characteristic	GBCA Exposure Group - Impaired Renal Function.	Total	GBCA Exposure Group - Normal Renal Function.	GBCA Naive - Control Group With Impaired Renal Function.	GBCA Naive - Control Group With Normal Renal Function.
Age, Continuous	74.6 years STANDARD_DEVIATION 7.37	69.5 years STANDARD_DEVIATION 10.65	64 years STANDARD_DEVIATION 10.5	78.4 years STANDARD_DEVIATION 5.28	70 years STANDARD_DEVIATION 10.88
Height	158.9 cm STANDARD_DEVIATION 9.83	163 cm STANDARD_DEVIATION 10.63	164.1 cm STANDARD_DEVIATION 11.08	162.6 cm STANDARD_DEVIATION 7.58	174 cm STANDARD_DEVIATION 5.86
Race and Ethnicity Not Collected	—	0 Participants	—	—	—
Sex: Female, Male Female	20 Participants	52 Participants	24 Participants	6 Participants	2 Participants
Sex: Female, Male Male	9 Participants	40 Participants	21 Participants	5 Participants	5 Participants
Weight	66.7 kg STANDARD_DEVIATION 19.01	74.2 kg STANDARD_DEVIATION 20.03	76 kg STANDARD_DEVIATION 21.09	76.6 kg STANDARD_DEVIATION 14.86	90 kg STANDARD_DEVIATION 13.08

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	2 / 74	0 / 18
other Total, other adverse events	35 / 74	10 / 18
serious Total, serious adverse events	3 / 74	2 / 18