An interventional study of Gadolinium analysis in bone and tissue samples in Focus: Long-term Retention of Gadolinium-based Contrast Agent, sponsored by Navitas Life Sciences GmbH. Completed at 16 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-09-28.
Sponsored by Navitas Life Sciences GmbH · Not applicable, Interventional, and Screening
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.
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.
This is the only study on the registry with Navitas Life Sciences GmbH as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Main Inclusion Criteria:
Patient belongs to one of the following subgroups with respect to the number of GBCA doses received and the status of their renal function:
Main Exclusion Criteria:
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.
Concentration of Total Gadolinium in Trabecular Bone
Concentration of total Gd in trabecular bone determined by ICP-MS
Time frame: 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
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
| Milestone | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function. |
|---|---|---|---|---|
| Started | 45 | 29 | 7 | 11 |
| Completed | 45 | 29 | 7 | 11 |
| Not completed | 0 | 0 | 0 | 0 |
Concentration of total Gd in trabecular bone determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Total Gadolinium in Trabecular Bone | 0.335 ± 476.7 | 0.783 ± 413.8 | 0 ± 0 | 0 ± 0 |
Concentration of total Gd in cortical bone determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Total Gadolinium in Cortical Bone | 0.298 ± 467.5 | 0.680 ± 410.3 | 0 ± 0 | 0 ± 0 |
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.
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function. |
|---|---|---|---|---|
| Concentration of Total Gd in Skin Tissue Samples | 0 ± 0 | 0 ± 0 | 0 ± 0 | 0 ± 0 |
Concentration of calcium in skin tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Calcium in Skin Tissue Samples | 653.268 ± 65.9 | 651.478 ± 55.6 | 474.377 ± 78.8 | 790.700 ± 105.8 |
Concentration of calcium in cortical bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Calcium in Cortical Bone Tissue Samples | 96908.336 ± 31.8 | 92491.896 ± 34 | 142662.680 ± 11.8 | 118447.534 ± 25.5 |
Concentrations of phosphorus in cortical bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Phosphorus in Cortical Bone Tissue Samples | 52361.735 ± 30 | 50247.073 ± 32.1 | 73151.974 ± 12.7 | 62689.679 ± 21.6 |
Concentrations of sodium in cortical bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Sodium in Cortical Bone Tissue Samples | 5642.001 ± 22.3 | 5768.821 ± 19.2 | 5437.226 ± 15.6 | 5511.498 ± 28.2 |
Concentrations of zinc in cortical bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Zinc in Bone Tissue Samples (Cortical) | 78.516 ± 29 | 79.900 ± 24.7 | 92.622 ± 12.1 | 89.539 ± 19.1 |
Concentration of potassium in bone (cortical) tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Potassium in Cortical Bone Tissue Samples | 488.128 ± 41.5 | 543.211 ± 61.9 | 541.822 ± 51.1 | 426.705 ± 65.4 |
Concentrations of iron in bone (cortical) tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Iron in Cortical Bone Tissue Samples | 38.807 ± 71.9 | 41.116 ± 118.9 | 57.069 ± 88.5 | 32.293 ± 109.8 |
Concentrations of calcium in trabecular bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Calcium in Trabecular Bone Tissue Samples | 124671.921 ± 22.2 | 116601.987 ± 24.2 | 145859.369 ± 20.3 | 143735.414 ± 11.5 |
Concentrations of phosphorus in bone (trabecular) tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Phosphorus in Trabecular Bone Tissue Samples | 65887.298 ± 17.7 | 62333.483 ± 18.4 | 74988.227 ± 20.8 | 74435.230 ± 11.7 |
Concentrations of sodium in trabecular bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Sodium in Trabecular Bone Tissue Samples | 4743.199 ± 19.7 | 4514.245 ± 19.5 | 4681.874 ± 13.8 | 4580.294 ± 14.7 |
Concentrations of zinc in trabecular bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Zinc in Trabecular Bone Tissue Samples | 83.812 ± 29 | 85.312 ± 30.2 | 89.849 ± 15.4 | 93.524 ± 18.3 |
Concentrations of potassium in trabecular bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Potassium in Trabecular Bone Tissue Samples | 394.953 ± 57.2 | 461.425 ± 81.9 | 679.490 ± 85.8 | 340.698 ± 48.6 |
Concentrations of iron in trabecular bone tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Iron in Trabecular Bone Tissue Samples | 40.142 ± 96.8 | 42.889 ± 116.9 | 62.371 ± 180.5 | 23.709 ± 68.7 |
Concentrations of phosphorus in skin tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Phosphorus in Skin Tissue Samples | 1023.978 ± 36.9 | 1038.525 ± 32.2 | 1075.359 ± 34.1 | 1129.268 ± 52.7 |
Concentrations of sodium in skin tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Sodium in Skin Tissue Samples | 3711.129 ± 42.5 | 4146.187 ± 49.9 | 4660.517 ± 36.6 | 4871.197 ± 42.9 |
Concentrations of zinc in skin tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentrations of Zinc in Skin Tissue Samples | 24.639 ± 59.5 | 28.767 ± 55.7 | 27.692 ± 112.3 | 23.537 ± 32.9 |
Concentration of potassium in skin tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Potassium in Skin Tissue Samples | 1011.939 ± 41.7 | 1132.855 ± 45.1 | 1418.726 ± 31.8 | 1121.846 ± 34.4 |
Concentration of iron in skin tissue samples determined by ICP-MS
| micrograms/gram | GBCA Exposure Group - Normal Renal Function | GBCA Exposure Group - Impaired Renal Function | GBCA Naive - Control Group With Normal Renal Function | GBCA Naive - Control Group With Impaired Renal Function |
|---|---|---|---|---|
| Concentration of Iron in Skin Tissue Samples | 69.452 ± 86.4 | 103.432 ± 101.8 | 145.362 ± 36.4 | 99.477 ± 79.2 |
Collected over Any AE occurring while a patient was in the study (from informed consent until follow-up visit 2 (visit 4 in case of second surgery) taking place approximately within 10-14 days post-surgery).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| GBCA Exposure Group | 2/74 (2.7%) | 3/74 (4.1%) | 35/74 (47.3%) |
| GBCA Naive Control Group | 0/18 (0%) | 2/18 (11.1%) | 10/18 (55.6%) |
| Event | GBCA Exposure Group | GBCA Naive Control Group |
|---|---|---|
| PneumoniaInfections and infestations | 0/74 | 1/18 |
| DeliriumPsychiatric disorders | 0/74 | 1/18 |
| Renal FailureRenal and urinary disorders | 0/74 | 1/18 |
| Cardiac Failure CongestiveCardiac disorders | 1/74 | 0/18 |
| OverdoseInjury, poisoning and procedural complications | 1/74 | 0/18 |
| Acute Respiratory FailureRespiratory, thoracic and mediastinal disorders | 1/74 | 0/18 |
| Nephrogenic Systemic FibrosisSkin and subcutaneous tissue disorders | 0/74 | 0/18 |
| Event | GBCA Exposure Group | GBCA Naive Control Group |
|---|---|---|
| Injury, Poisoning And Procedural ComplicationsInjury, poisoning and procedural complications | 12/74 | 4/18 |
| Gastrointestinal DisordersGastrointestinal disorders | 13/74 | 2/18 |
| Psychiatric DisordersPsychiatric disorders | 11/74 | 3/18 |
| Vascular DisordersVascular disorders | 10/74 | 2/18 |
| Musculoskeletal And Connective Tissue DisordersMusculoskeletal and connective tissue disorders | 9/74 | 0/18 |
| Infections And InfestationsInfections and infestations | 5/74 | 2/18 |
| Renal And Urinary DisordersRenal and urinary disorders | 2/74 | 2/18 |
| Blood And Lymphatic System DisordersBlood and lymphatic system disorders | 0/74 | 2/18 |
| General Disorders And AdministrationGeneral disorders | 8/74 | 1/18 |
| InvestigationsInvestigations | 5/74 | 0/18 |
| Age, Continuous(years) | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function. | Total |
|---|---|---|---|---|---|
| Mean | 64 ± 10.5 | 74.6 ± 7.37 | 70 ± 10.88 | 78.4 ± 5.28 | 69.5 ± 10.65 |
| Sex: Female, Male(Participants) | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function. | Total |
|---|---|---|---|---|---|
| Female | 24 | 20 | 2 | 6 | 52 |
| Male | 21 | 9 | 5 | 5 | 40 |
| Race and Ethnicity Not Collected(Participants) | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function. | Total |
|---|---|---|---|---|---|
| Count of participants | — | — | — | — | 0 |
| Height(cm) | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function. | Total |
|---|---|---|---|---|---|
| Mean | 164.1 ± 11.08 | 158.9 ± 9.83 | 174 ± 5.86 | 162.6 ± 7.58 | 163 ± 10.63 |
| Weight(kg) | GBCA Exposure Group - Normal Renal Function. | GBCA Exposure Group - Impaired Renal Function. | GBCA Naive - Control Group With Normal Renal Function. | GBCA Naive - Control Group With Impaired Renal Function. | Total |
|---|---|---|---|---|---|
| Mean | 76 ± 21.09 | 66.7 ± 19.01 | 90 ± 13.08 | 76.6 ± 14.86 | 74.2 ± 20.03 |
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