Focus: Long-term Retention of Gadolinium-based Contrast AgentNCT01853163

Long-Term Retention of Gadolinium in Bone

A study testing Gadolinium analysis in bone and tissue samples in people with Focus: Long-term Retention of Gadolinium-based Contrast Agent, run by Navitas Life Sciences GmbH at 16 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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 >… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Focus: Long-term Retention of Gadolinium-based Contrast Agent
What is being tested?: Gadolinium analysis in bone and tissue samples
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 92 participants
Where: 16 sitesin 6 countries
Study dates: 6 May 2013to 17 Dec 2018
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

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.

Trial locations and contacts

16 sites in 6 countries.

Country

City, postcode or hospital

16 sites in 6 countries

Turkey (Türkiye)5 sites

Koc University Hospital, Orthopaedics and Traumatology Department
Istanbul, 34010
Acibadem Hospital, Department of Orthopaedics and Traumatology
Istanbul, 34303
Fatih Sultan Mehmet Training and Research Hospital, Department of Orthopedics and Traumatology
Istanbul, 34752
Istanbul Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi
Istanbul
Dokuz Eylul University Tıp Faculty
Izmir, 35340

Other trials in Turkey (Türkiye)

Germany3 sites

University Hospital Halle (Saale)
Halle, 06097
University Hospital Magdeburg
Magdeburg, 39120
University Hospital Würzburg
Würzburg, 97074

Other trials in Germany

Spain3 sites

Hospital Universitario Fundación Alcorcón
Alcorcón, 28922
Hospital Vall d'Hebron
Barcelona, 08035
H.G.U. Gregorio Marañón
Madrid, 28007

Other trials in Spain

Japan2 sites

Fukuoka Orthopaedic Hospital
Fukuoka, 815-0063
Nissan Tamagawa Hospital
Tokyo, 158-0095

Other trials in Japan

South Korea2 sites

Asan Medical Center Orthopedic Surgery
Seoul, 05505
SMG-SNU Boramae Medical Center
Seoul, 156-707

Other trials in South Korea

United States1 site

Cedar-Sinai Medical Center
Los Angeles, California, 90048

Other trials in United States

About this study

Official title: 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

Read the 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.

Conditions: Focus: Long-term Retention of Gadolinium-based Contrast Agent
Being tested: Gadolinium analysis in bone and tissue samples
Keywords: Gadolinium, Contrast Agent, Long-term retention

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Gadolinium analysis in bone and tissue samplesProcedure or surgery
Gadolinium analysis in bone and tissue samples from patients undergoing an orthopaedic surgical procedure who had received GBCAs in the past.

Study groups in NCT01853163
Study group	Role	What they receive
GBCA	Other	Patients who have received GBCAs in the past Receives: Procedure: Gadolinium analysis in bone and tissue samples

What is being measured

The primary outcome is the main question the study is designed to answer.

Concentration of Total Gadolinium in Trabecular Bone
Concentration of total Gd in trabecular bone determined by ICP-MS
Measured: 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
Measured: Day 0 (visit 2, surgery); optional visit 6 (second surgery)

Secondary outcomes (19)

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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Day 0 (visit 2, surgery); optional visit 6 (second surgery)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 May 201317 Dec 2018

First posted14 May 2013 (estimated)
Study start6 May 2013
Primary completion5 Dec 2018
Study completion17 Dec 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Focus: Long-term Retention of Gadolinium-based Contrast AgentStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Screening
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 92 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01853163
Sponsor's protocol ID: ALS-Gd64/001
Status last verified: Jun 2020
First submitted: 10 May 2013
Last updated: 28 Sep 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Study at a glance

From the registry record, last updated by the sponsor on 28 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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
ClinicalTrials.gov ID: NCT01853163
Acronym / sponsor ID: ALS-Gd64/001
Conditions: Focus: Long-term Retention of Gadolinium-based Contrast Agent
Keywords: Gadolinium, Contrast Agent, Long-term retention
Study type: Interventional
Recruitment status: Completed
Enrolment: 92 participants (actual)
Lead sponsor: Navitas Life Sciences GmbHIndustry (pharma, biotech, devices)
Collaborators: Bayer, GE Healthcare, Guerbet
Study start: 6 May 2013 (actual)
Primary completion: 5 Dec 2018 (actual)
Study completion: 17 Dec 2018 (actual)
First posted: 14 May 2013 (estimated)
Results: Posted 28 Sep 2022

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

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 design

Primary purpose: Screening
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
GBCA	Other	Procedure: Gadolinium analysis in bone and tissue samplesPatients who have received GBCAs in the past

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Gadolinium analysis in bone and tissue samplesGadolinium analysis in bone and tissue samples from patients undergoing an orthopaedic surgical procedure who had received GBCAs in the past.	Procedure or surgery	GBCA

Primary outcome

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

19 secondary outcomes

Concentration of Total Gd in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Calcium in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Calcium in Cortical Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Phosphorus in Cortical Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Sodium in Cortical Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Zinc in Bone Tissue Samples (Cortical)
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Potassium in Cortical Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Iron in Cortical Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Calcium in Trabecular Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Phosphorus in Trabecular Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Sodium in Trabecular Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Zinc in Trabecular Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Potassium in Trabecular Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Iron in Trabecular Bone Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Phosphorus in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Sodium in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentrations of Zinc in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Potassium in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)
Concentration of Iron in Skin Tissue Samples
Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)

Results and safety

Results posted to the registry on 28 Sep 2022, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
GBCA Exposure Group - Normal Renal Function.	45	45
GBCA Exposure Group - Impaired Renal Function.	29	29
GBCA Naive - Control Group With Normal Renal Function.	7	7
GBCA Naive - Control Group With Impaired Renal Function.	11	11

Primary outcome: Concentration of Total Gadolinium in Trabecular Bone

Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery). Geometric mean (Geometric Coefficient of Variation). Unit: micrograms/gram

Measure	GBCA Exposure Group - Normal Renal Function n = 45	GBCA Exposure Group - Impaired Renal Function n = 29	GBCA Naive - Control Group With Normal Renal Function n = 7	GBCA Naive - Control Group With Impaired Renal Function n = 11
Value	0.335 (476.7)	0.783 (413.8)	0 (0)	0 (0)

Population analysed: Note: Below values for both control groups (0 (0%)) are "NA = Descriptive statistics not performed since it does not satisfy 2/3 of GBCA concentration values are available and above BLQ", 2 patients of the control group with impaired renal function have values \> BLQ, max 1.921 ug/g.

Primary outcome: Concentration of Total Gadolinium in Cortical Bone

Time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery). Geometric mean (Geometric Coefficient of Variation). Unit: micrograms/gram

Measure	GBCA Exposure Group - Normal Renal Function n = 45	GBCA Exposure Group - Impaired Renal Function n = 29	GBCA Naive - Control Group With Normal Renal Function n = 7	GBCA Naive - Control Group With Impaired Renal Function n = 11
Value	0.298 (467.5)	0.680 (410.3)	0 (0)	0 (0)

19 secondary outcomes are reported in the full results.

Adverse events

Time frame: 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).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
GBCA Exposure Group	3 of 74 (4.1%)	35 of 74 (47.3%)	2 of 74
GBCA Naive Control Group	2 of 18 (11.1%)	10 of 18 (55.6%)	0 of 18

Limitations and caveats (from the sponsor): Due to EMA recommendation in July 2017 to restrict the use of linear gadolinium based contrast agents in body scans, the enrollment of impaired renal patients with a history of linear GdCA was restricted.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Christoph Lohmann, Professor MD principal investigator

University Hospital Magdeburg, Germany

16 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Turkey (Türkiye), Germany, Spain, Japan, South Korea and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Concentration of Total Gadolinium in Trabecular Bone (time frame: Day 0 (visit 2, surgery); optional visit 6 (second surgery)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01853163.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2022.