UMIN-CTR Clinical Trial

Basic information
Public 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.
Acronym	Long-Term Retention of Gadolinium in Bone
Scientific 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.
Scientific Title:Acronym	Long-Term Retention of Gadolinium in Bone
Region	Japan Asia(except Japan) North America Europe

Condition
Condition	- MRI with Gadolinium Contrast Agent received (independent of indication) - Hip or knee surgery planned
Classification by specialty	Not applicable
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	Primary objective: To prospectively explore the potential for long-term retention of Gd in the bones of patients who have received a single dose of GdCA or multiple doses of the same GdCA, with moderate or severe renal impairment or stable renal function (estimated glomerular filtration rate > 60 ml/min/1.73 m2) at the time of GdCA injection. Secondary objectives: - To evaluate skin samples for concentration of Gd - To evaluate bone and skin samples for concentrations of calcium, phosphorus, sodium, iron, zinc and potassium - To evaluate skin samples for any dermatopathological changes that may be associated with Nephrogenic Sys¬temic Fibrosis (NSF) - To describe potential co-factors for NSF, susceptibility fac¬tors and drug treatments with potential impact on bone metabolism
Basic objectives2	Safety
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Primary evaluation variables: - Concentration of total Gd in trabecular bone (determined by ICP-MS). - Concentration of total Gd in cortical bone (determined by ICP-MS).
Key secondary outcomes	Secondary evaluation variables: - Concentration of total Gd in skin tissue samples (determined by ICP-MS), collected at the time of hip or knee replacement surgery, from a biopsy from the edge of the sur¬gical wound. - Concentrations of calcium, phosphorus, sodium, iron, zinc and potassium in bone (both trabecular and cortical) and skin tissue samples (determined by ICP-MS or al-ternatively ICP-AES if the feasibility evaluation of ICP-MS does not show reliable re¬sults). - Histopathological evaluation of skin samples with regard to the possibility of findings associated with NSF (determined by an experienced dermatopathologist). - Description of potential co-factors for NSF, susceptibility factors and drug treatments with potential impact on bone metabolism.

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -but assessor(s) are blinded
Control	No treatment
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Diagnosis
Type of intervention	Maneuver
Interventions/Control_1	Skin Sample collection
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	18 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	1.Patient (Pt.) must be at least 18 years of age 2.Pt. scheduled for hip or knee replacement 3.Pt. is scheduled to have sufficient bone removed during the hip or knee surgical replacement procedure and sufficient non-scarred skin tissue from the edge of the surgical incision to permit sample collection, in the investigator's medical opinion 4.Pt. agreed to have bone and skin samples collected at the time of the surgical procedure(s) 5.Pt.'s surgical procedure and subsequent remission will not be altered by studyspecific skin biopsies, in the investigator's medical opinion 6.Pt. is fully informed about the study and has signed the informed consent form Patients having received GdCA 7.Pt. belongs to one of the following subgroups with respect to the no. of GdCA doses received and the status of their renal function a)Pt. has stable severe renal impairment* and has received one GdCA injection at the standard dose b)Pt. has stable severe renal impairment* and has received more than one injection of the same GdCA c)Pt. has stable moderate renal impairment2* and has received one GdCA injection at the standard dose d)Pt. has stable moderate renal impairment2* and has received more than one injection of the same GdCA e)Pt. has stable renal function3* and has received one GdCA injection at the standard dose f)Pt. has stable renal function3* and has received more than one injection of the same GdCA 8.A minimum of 3 months have elapsed between GdCA dose and scheduled hip or knee replacement 9.Pt. GdCA history, including dose(s), date(s), and product(s) administered is complete and accurate GdCA naive patients (control group) 10.Pt. has never received GdCA before hip / knee replacement 11.Pt. belongs to one of the following renal function categories g)Pt. has stable severe renal impairment* h)Pt. has stable moderate renal impairment2* i)Pt. has stable renal function3* *:eGFR<30 2*:eGFR within the range 30 to 60 3*:eGFR>60 (eGFR units:ml/min/1.73m2)
Key exclusion criteria	No patient may enter the study if any of the following exclusion criteria are fulfilled: 1. Patient has received different GdCAs. 2. Patient has received intra-articular GdCA or per any other non-i.v. route. 3. Patient has received or is scheduled to receive GdCA within 3 months prior to the date of hip or knee replacement surgery and study sample collection procedures. 4. Patient has received any investigational product or has participated in any other clinical trial within 30 days prior to enrolling in this study. 5. Patient suspected of, or diagnosed with, tumour in knee / hip bone, metastatic bone and bone marrow disease in knee / hip. Note: Patients shall not be excluded for other bone diseases with the exception of those with bone cancer as specified in exclusion criterion 5. 6. Patient has diagnosed or suspected NSF at time of enrolment. Note: Patients shall not be excluded for diagnosis of NSF subsequent to enrolment. 7. Patient presents with scarring in the region(s) of the scheduled surgical procedure(s) or of the skin sampling location, to the extent that collection of an unscarred skin sample is not feasible. 8. Patient has a close affiliation with the investigational site; e.g., a relative of the investigator, dependent person (e.g., employee or student of the investigational site).
Target sample size	350

Research contact person
Name of lead principal investigator	1st name Middle name Last name Christoph Lohmann, Prof., MD
Organization	University Clinic Magdeburg A. ö. R.
Division name	Orthopedics University Clinic
Zip code
Address	Leipziger Str. 44, 39120 Magdeburg, Germany
TEL	+49(0)391-67-14000
Email	christoph.lohmann@med.ovgu.

Public contact
Name of contact person	1st name Middle name Last name Masami Fujino
Organization	EPS Associates Co., Ltd.
Division name	Clinical Development Dept. 1 Pharmaceutical Development Project Division
Zip code
Address	2-23 Shimomiyabicho, Shinjuku-ku, Tokyo, 162-0822, Japan
TEL	03-3868-5268
Homepage URL
Email	m.fujino.yi@eps-associates.com

Sponsor
Institute	Ecron Acunova GmbH
Institute
Department

Funding Source
Organization	Bayer Pharma AG, Covidien Pharmaceuticals AG, GE Healthcare AS, Guerbet SA
Organization
Division
Category of Funding Organization	Outside Japan
Nationality of Funding Organization	Germany, Switzerland, UK, France

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	YES
Study ID_1	NCT01853163
Org. issuing International ID_1	ClinicalTrials.gov
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2013 Year 10 Month 01 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Suspended
Date of protocol fixation	2012 Year 12 Month 19 Day
Date of IRB
Anticipated trial start date	2013 Year 09 Month 11 Day
Last follow-up date	2014 Year 10 Month 01 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2013 Year 09 Month 30 Day
Last modified on	2015 Year 08 Month 04 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013571

Research Plan
Registered date	File name

Research case data specifications
Registered date	File name

Research case data
Registered date	File name

Contact us.