Renal safety evaluation after dotarem-enhanced MRI compared with non-enhanced MRI in patients at high risk of developing contrast medium induced nephropathy - RESCUE

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-000229-23-IT
• Date of registration: 23/03/2010
• Prospective Registration: No
• Primary sponsor: GUERBET
• Public title: Renal safety evaluation after dotarem-enhanced MRI compared with non-enhanced MRI in patients at high risk of developing contrast medium induced nephropathy - RESCUE
• Scientific title: Renal safety evaluation after dotarem-enhanced MRI compared with non-enhanced MRI in patients at high risk of developing contrast medium induced nephropathy - RESCUE
• Date of first enrolment: 01/03/2010
• Target sample size: 134
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-000229-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: no Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: comparative descriptive If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Esame senza iniezione di mezzo di contrasto

Countries of recruitment

France, Italy, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Male or female, aged ≥ 18 years; Female of childbearing potential must have effective contraception (contraceptive pill or Intra-Uterine Device), or be surgically sterilized, or post-menopausal (minimum 12 months of amenorrhea) or must have a documented negative urine or blood pregnancy test at screening; Patient presenting with a known stable stage III to stage IV renal insufficiency according to the K/DOQI definition, i.e., 15 < estimated GFR < 60 ml/min/1.73m? according to MDRD formula; stability will be demonstrated with 2 consecutive values (within 15% of each other): a previous value obtained at least one week in advance (not more than 6 months in advance) and the most recent one obtained prior to the study procedure, on the same day or on the day before; Patient scheduled to undergo a contrast enhanced MRI or unenhanced MRI examination to specify a diagnosis; Patient receiving angiotensin-converting enzyme inhibitors, angiotensine II receptor blockers ( sartans ), diuretics and fibrates, must be receiving these drug(s) at stable dosage(s) for at least 2 weeks; in addition the dosage(s) should not be modified for the whole study duration (i.e., until 72 hours ? 24hrs or 14 days after the imaging procedure); Patient able to understand and having provided written informed consent to participate in the trial; Patient for whom blood samples can be obtained on the day of the imaging procedure or on the day before and 72 hours (? 24 hrs) after the examination; Patient with National health insurance.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patient with a contraindication to MRI (e.g., pacemaker, aneurysm clip, severe claustrophobia, metallic joint replacement or others according to the imaging laboratory`s standard practice); Patient who has a diagnosis of a hemodynamic instability (cardiogenic shock persistent systolic pressure < 90 requiring inotropic support) or acute myocardial infraction within 15 days prior the inclusion; Patient who needs haemodialysis; Patient with known allergy to gadolinium chelates (only applicable for patient undergoing Dotarem-enhanced MRI); Patient receiving anticalcineurine drugs, such as ciclosporine, unless the patient has been having a stable (variation ≤ 15%) creatinine level for at least 6 months, as demonstrated with available creatinine values, and has been receiving the drug at stable dosage for at least 6 months; this dosage should not be modified for the whole study duration (i.e., until 72 hours ? 24hrs or 14 days after the imaging procedure); Patient receiving any other medication known to be nephrotoxic or to cause increases in serum creatinine level (e.g., selective inhibitors of cyclo-oxygenase 2, anti-vascular Endothelium Growth Factors, vancomycine, aciclovir, aminoglycosides, amphotericin B, polymixin, platinium complexes, non-steroidal anti-inflammatory treatment except acetyl salicylic acid, etc.) within 2 weeks before first blood sample and for the whole study duration (i.e., until 72 hours ? 24hrs or 14 days after the imaging procedure); Patients planned to either undergo surgery or receive chemotherapy within 72 hours post-procedure (i.e., before the 72 hours post-procedure blood test); Patient having had an imaging procedure (MRI or CT imaging, with contrast medium or not) within 7 days of entering this protocol; Patient with a planned imaging procedure (MRI or CT imaging, with contrast medium or not) within 72 hours post-procedure; Patient having participated in any investigational drug study within 30 days prior the study enrolment or planned to participate within 72 hours post-procedure; Any condition which, based on the investigator`s clinical judgement, would prevent the patient from completing all trial assessments and visits; Patient under guardianship and/or inability or unwillingness to cooperate with the requirements of this trial; Patient with newly discovered unstable diabetes (i.e. < 1 month, glycaemia ≥ 2.5g/l).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Patient with at least moderate renal insuffiency and scheduled to undergo a contrast enhanced MRI or unenhanced MRI.
MedDRA version: 12.1 Level: LLT Classification code 10038474 Term: Renal insufficiency

Intervention(s)

Trade Name: DOTAREM*INFUS 20ML 0,5MMOL/ML
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ACIDO GADOTERICO
CAS Number: 72573-82-1
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 5.5864-

Primary Outcome(s)

Main Objective: To assess in at risk patients (patients with at least moderate renal insufficiency) the frequency of contrast-induced nephropathy after Dotarem-enhanced MRI, in comparison with the frequency of nephropathy after unenhanced MRI and to observe a non-inferiority between both procedures regarding these frequencies.

Secondary Objective: -To confirm the clinical and biological safety of DOTAREM by assessing vital signs, laboratory parameters and adverse events through a 72?24 hours post treatment (DOTAREM) or post procedure follow-up period. -To assess the serum creatinine level fluctuation in term of mean difference between baseline and 72?24 hours after examination. -To evaluate the estimated Glomerular Filtration Rate fluctuation in term of percentage and mean difference between baseline and 72?24 hours after examination. Estimated GFR will be assessed using the MDRD study equation. -If possible, to assess the potential influence of hydration protocol and/or prophylactic treatment on the renal function -In case of rise in Serum creatinine level at 72?24 hours of at least 25% or 0.5mg/dl (44.2?mol/l), to observe the percentage of patients returned at baseline level 14 days after the imaging procedure.

Primary end point(s): The evaluation of the renal tolerance after both procedures (MRI and DOTAREM-MRI) will be done by assessing the serum creatinine levels from blood sampling taken within 24 hours before the imaging procedure and at 72?24 hours after the procedure. This study will calculate in the two groups the percentage of patients presenting with a significant creatinine level increase according to the approach described hereafter. Significant creatinine level increase (Nephrotoxicity) will be defined as a rise in serum creatinine level at 72?24 hours of at least 25% or 0.5mg/dl (=44.2?mol/l) compared to baseline.

Secondary ID(s)

2007-000229-23-FR

DGD 44-044