Renal Safety Evaluation After Dotarem®-Enhanced MRI (RESCUE)

• ClinicalTrials.gov Identifier: NCT00650845
• Recruitment Status: Completed
• First Posted: April 2, 2008
• Results First Posted: June 9, 2015
• Last Update Posted: June 9, 2015
• Sponsor: Guerbet
• Information provided by (Responsible Party): Guerbet

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Renal Insufficiency	Drug: Dotarem®-enhanced MRI; Other: non-enhanced MRI	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 135 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Renal Safety Evaluation After Dotarem®-Enhanced MRI Compared With Non-enhanced MRI in Patients at High Risk of Developing Contrast Medium Induced Nephropathy
• Study Start Date: January 2008
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: August 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dotarem®-enhanced MRI; Patients undergoing Dotarem®-enhanced MRI for diagnostic purposes	Drug: Dotarem®-enhanced MRI; Single IV administration before MRI exam; Other Names: Gadoterate meglumine; Gadoteric acid
Non-enhanced MRI; Patients undergoing non-enhanced MRI for diagnostic purposes	Other: non-enhanced MRI; non injected MRI; Other Name: unenhanced MRI

Outcome Measures

Primary Outcome Measures :

1. 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. [ Time Frame: 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.
2. 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. [ Time Frame: 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 :

1. Percent Change of Serum Creatinine Level From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population. [ Time Frame: 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.
2. Percent Change of Serum Creatinine Level Variation From Baseline to 72±24 Hours After Examination, in the Per Protocol Population [ Time Frame: 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.
3. Percent Change of Estimated Glomerular Filtration Rate (eGFR) Values From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population [ Time Frame: 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.
4. eGFR Values Variation Between Baseline and 72±24 Hours After Examination, in the Per Protocol Population [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Belgium

Onze Lievevrouwziekenhuis

Aalst, Belgium, 9300

University Hospital Ghent

Gent, Belgium, 9000

Alg. Inwendige Ziekten -Nierziekten

Roeselare, Belgium, 8800

France

Groupe Hospitalier Pellegrin

Bordeaux, France, 33076

Hôpital A. Calmette

Lille, France, 59037

Hôpital Edouard Herriot

Lyon, France, 69437

Hopital Pitie Salpetriere

Paris, France, 75013

Hopital Bichat

Paris, France, 75018

Hôpital Tenon

Paris, France, 75020

CHU Strasbourg

Strasbourg, France, 67000

Hôpital Trousseau

Tours, France, 37044

Italy

Azienda Ospedaliera Universitaria di Ferrara

Ferrara, Italy, 44100

Ente Ospedaliero Ospedali Galliera,

Genova, Italy, 16128

Spain

Hospital San Carlos

Madrid, Spain, 28040

Hospital Dr PESET

Valencia, Spain, 46017

Sponsors and Collaborators

Guerbet

Investigators

• Principal Investigator: Gilbert Deray, Pr, MD, PhD; Groupe Hospitalier Pitie-Salpetriere

More Information

• Responsible Party: Guerbet
• ClinicalTrials.gov Identifier: NCT00650845
• Other Study ID Numbers: DGD-44-044
• First Posted: April 2, 2008
• Results First Posted: June 9, 2015
• Last Update Posted: June 9, 2015
• Last Verified: March 2015

Keywords provided by Guerbet:

contrast-induced nephropathy, creatinemia

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; Chelating Agents; Sequestering Agents; Molecular Mechanisms of Pharmacological Action