Renal Safety Evaluation After Dotarem®-Enhanced MRI

Study Overview
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Brief Summary
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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
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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.

Official Title
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Renal Safety Evaluation After Dotarem®-Enhanced MRI Compared With Non-enhanced MRI in Patients at High Risk of Developing Contrast Medium Induced Nephropathy

Conditions
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Renal Insufficiency

Intervention / Treatment
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* Drug: Dotarem®-enhanced MRI
* Other: non-enhanced MRI


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dotarem®-enhanced MRI<br>Patients undergoing Dotarem®-enhanced MRI for diagnostic purposes | Drug: Dotarem®-enhanced MRI<br>* Single IV administration before MRI exam<br>* Other names: Gadoteric acid;|
| Other: Non-enhanced MRI<br>Patients undergoing non-enhanced MRI for diagnostic purposes | Other: non-enhanced MRI<br>* non injected MRI<br>* Other names: unenhanced MRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | baseline pre MRI and 3 days post MRI | 
| 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. | 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. | Baseline pre MRI and 3 days post MRI | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change of Serum Creatinine Level From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population. | 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. | Baseline pre MRI and 3 days post MRI | 
| Percent Change of Serum Creatinine Level Variation From Baseline to 72±24 Hours After Examination, in the Per Protocol Population | 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. | Baseline pre MRI and 3 days post MRI | 
| Percent Change of Estimated Glomerular Filtration Rate (eGFR) Values From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population | 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. | Baseline pre MRI and 3 days post MRI | 
| eGFR Values Variation Between Baseline and 72±24 Hours After Examination, in the Per Protocol Population | 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. | Baseline pre MRI and 3 days post MRI | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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contrast-induced nephropathy, creatinemia