E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient with at least moderate renal insuffiency and scheduled to undergo a contrast enhanced MRI or unenhanced MRI. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038474 |
E.1.2 | Term | Renal insufficiency |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
-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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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). |
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Esame senza iniezione di mezzo di contrasto |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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L`ultima visita dell`ultimo paziente |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |