Renal Safety Evaluation After Dotarem®-Enhanced MRI

Phase 4

Completed

Conditions: Renal Insufficiency

Interventions: Drug: Dotarem®-enhanced MRI
Other: non-enhanced MRI

Registration Number: NCT00650845

Lead Sponsor: Guerbet

Brief Summary: Although there is a well documented risk of acute renal failure with the iodinated contrast agents, the implication of intravenous gadolinium-based contrast agents in nephrotoxicity remains controversial. The aim of this study was to evaluate the safety profile of gadoterate meglumine (Dotarem®) in patients with chronic renal insufficiency by evaluating the rate of patients experiencing contrast-induced nephrotoxicity following the injection of gadoterate meglumine.

Detailed Description: Patients with renal insufficiency not requiring hemodialysis and scheduled to undergo a contrast enhanced MRI or unenhanced MRI examination to specify a diagnosis, were selected for inclusion. Two groups of patients were defined on the basis of the planned imaging procedure selected to obtain a diagnosis: those undergoing a Dotarem®-enhanced MRI and those undergoing an unenhanced MRI.

A clinically significant increase in serum creatinine levels after the contrast-enhanced MRI exam was used as an indication of contrast induced nephrotoxicity. A blood test was performed 24h before the MRI in order to evaluate baseline creatinine values. 72h after the exam, a second blood test was performed. An increase in creatinemia above 25% from baseline levels was defined as a contrast-induced nephrotoxic reaction. The primary endpoint of the study assessed the percentage of patients presenting a contrast-induced nephrotoxic reaction in order to show a non inferiority of enhanced as compared to non-enhanced MRI exams.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 135

Inclusion Criteria

Male or female, > or equal 18 years ;
Patient with a known stable renal insufficiency ;
Patient scheduled to undergo an MRI examination to specify a diagnosis ;
Patient able to understand and provide written informed consent to participate in the trial ;

Exclusion Criteria

Patient with a contra-indication to MRI ;
Patient who has a diagnosis of an hemodynamic instability or acute myocardial infarction within 15 days prior the inclusion ;
Patient who needs hemodialysis ;
Patient with known allergy to gadolinium chelates ;
Patient receiving medications known to be nephrotoxic or to cause increases in serum creatinine level within 2 weeks before the inclusion ;
Patients planned to either undergo surgery or receive chemotherapy ;
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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dotarem®-enhanced MRI	Dotarem®-enhanced MRI	Patients undergoing Dotarem®-enhanced MRI for diagnostic purposes
Non-enhanced MRI	non-enhanced MRI	Patients undergoing non-enhanced MRI for diagnostic purposes

Primary Outcome Measures

Name	Time	Method
Number of Patients Presenting Contrast-induced Nephropathy as Defined by an Increase in Serum Creatinine Levels of a Least 25% Over Baseline Levels, in the Full Analysis Set Population.	baseline pre MRI and 3 days post MRI	Comparing the number of patients experiencing an increase of creatinine of at least 25% over baseline levels after Dotarem®-enhanced MRI and after non-enhanced MRI in patients with at least a moderate renal insufficiency.
Number of Patients Presenting Contrast-induced Nephropathy as Defined by an Increase in Serum Creatinine Levels of at Least 25% Over Baseline Levels, in the Per Protocol Population.	Baseline pre MRI and 3 days post MRI	Comparing the number of patients experiencing an increase of creatinine of at least 25% over baseline levels after Dotarem®-enhanced MRI and after non-enhanced MRI in patients with at least a moderate renal insufficiency.

Secondary Outcome Measures

Name	Time	Method
Percent Change of Serum Creatinine Level Variation From Baseline to 72±24 Hours After Examination, in the Per Protocol Population	Baseline pre MRI and 3 days post MRI	Serum creatinine levels were measured at baseline and at 72±24 hours after examination. The percentage of change in creatinemia from baseline was calculated for both the Dotarem® and the non-enhanced groups.
Percent Change of Serum Creatinine Level From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population.	Baseline pre MRI and 3 days post MRI	Serum creatinine levels were measured at baseline and at 72±24 hours after examination. The percentage of change in creatinemia from baseline was calculated for both the Dotarem® and the non-enhanced groups.
Percent Change of Estimated Glomerular Filtration Rate (eGFR) Values From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population	Baseline pre MRI and 3 days post MRI	eGFR was assessed using creatinemia and the Modification of Diet in Renal Disease (MDRD) study equation. eGFR were evaluated in terms of mean difference between the pre- and post-MRI procedure. The eGFR variation was expressed as a percentage of change from baseline values.
eGFR Values Variation Between Baseline and 72±24 Hours After Examination, in the Per Protocol Population	Baseline pre MRI and 3 days post MRI	eGFR (estimated Glomerular Filtration Rate) was assessed using creatinemia and the Modification of Diet in Renal Disease (MDRD) study equation. eGFR were evaluated in terms of mean difference between the pre- and post-MRI procedure. The eGFR variation was expressed as a percentage of change from baseline values.

Trial Locations

Locations (15): Hospital San Carlos
🇪🇸
Madrid, Spain
Alg. Inwendige Ziekten -Nierziekten
🇧🇪
Roeselare, Belgium
Hôpital A. Calmette
🇫🇷
Lille, France
Onze Lievevrouwziekenhuis
🇧🇪
Aalst, Belgium
Groupe Hospitalier Pellegrin
🇫🇷
Bordeaux, France
Hôpital Edouard Herriot
🇫🇷
Lyon, France
Hopital Pitie Salpetriere
🇫🇷
Paris, France
Hopital Bichat
🇫🇷
Paris, France
CHU Strasbourg
🇫🇷
Strasbourg, France
Azienda Ospedaliera Universitaria di Ferrara
🇮🇹
Ferrara, Italy
Hôpital Tenon
🇫🇷
Paris, France
Hôpital Trousseau
🇫🇷
Tours, France
Ente Ospedaliero Ospedali Galliera,
🇮🇹
Genova, Italy
Hospital Dr PESET
🇪🇸
Valencia, Spain
University Hospital Ghent
🇧🇪
Gent, Belgium