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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dotarem®-enhanced MRI | Experimental | Patients undergoing Dotarem®-enhanced MRI for diagnostic purposes |
|
| Non-enhanced MRI | Other | Patients undergoing non-enhanced MRI for diagnostic purposes |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dotarem®-enhanced MRI | Drug | Single IV administration before MRI exam |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gilbert Deray, Pr, MD, PhD | Groupe Hospitalier Pitie-Salpetriere | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Onze Lievevrouwziekenhuis | Aalst | 9300 | Belgium | |||
| University Hospital Ghent |
10 patients were screened but did not undergo the planned procedure: 7 were screen failures and 3 were included but dropped out prior to undergoing the planned procedure. Hence the total number of patients who were assigned to both groups is 132.
This study did not use randomization. Eligible patients who provided written consent were enrolled chronologically in each investigational center. A total of 142 patients were screened between 29 January 2008 and 05 May 2011, 135 of whom were included in 15 European centers, eight centers in France, three in Belgium, two in Spain and two in Italy.
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| ID | Title | Description |
|---|---|---|
| FG000 | Dotarem®-Enhanced MRI | Dotarem®: Single IV administration |
| FG001 | Non-enhanced MRI | non-enhanced MRI: non injected MRI |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dotarem®-Enhanced MRI | Dotarem®: Single IV administration before the MRI |
| BG001 | Non-enhanced MRI | non-enhanced MRI: non injected MRI |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Full analysis set population: all included patients with a pre and post-procedure blood sample for creatinine measures. | Posted | Number | Number of patients | baseline pre MRI and 3 days post MRI |
|
The period of observation for Adverse Events (AEs) collection extended from the time of patient informed consent until the end of his/her follow-up (i.e. 72 ±24hrs or 14 days after the imaging procedure) or until patient early withdrawal from the trial.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dotarem®-Enhanced MRI | Dotarem®: Single IV administration before the MRI |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hematoma | Vascular disorders | MedDRA 13.1 | Systematic Assessment | This adverse event was deemed not related to the injection of Dotarem® |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pierre Desché, MD - VP Development, Medical and Regulatory Affairs. | Guerbet | +33 1 45 91 50 00 | pierre.desche@guerbet-group.com |
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| ID | Term |
|---|---|
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| C072417 | gadoterate meglumine |
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| non-enhanced MRI | Other | non injected 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 |
| Ghent |
| 9000 |
| Belgium |
| Alg. Inwendige Ziekten -Nierziekten | Roeselare | 8800 | Belgium |
| Groupe Hospitalier Pellegrin | Bordeaux | 33076 | France |
| Hôpital A. Calmette | Lille | 59037 | France |
| Hôpital Edouard Herriot | Lyon | 69437 | France |
| Hopital Pitie Salpetriere | Paris | 75013 | France |
| Hopital Bichat | Paris | 75018 | France |
| Hôpital Tenon | Paris | 75020 | France |
| CHU Strasbourg | Strasbourg | 67000 | France |
| Hôpital Trousseau | Tours | 37044 | France |
| Azienda Ospedaliera Universitaria di Ferrara | Ferrara | 44100 | Italy |
| Ente Ospedaliero Ospedali Galliera, | Genova | 16128 | Italy |
| Hospital San Carlos | Madrid | 28040 | Spain |
| Hospital Dr PESET | Valencia | 46017 | Spain |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Age, Categorical | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
non-enhanced MRI: non injected MRI |
|
|
|
| Secondary | 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. | Full analysis set population:all included patients with a pre and post-procedure blood sample for creatinine measurement. | Posted | Mean | Standard Deviation | Percentage of change from baseline | Baseline pre MRI and 3 days post MRI |
|
|
|
|
| Primary | 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. | Per protocol population: This population is comprised of the full analysis set population (i.e. all included patients with a pre and post-procedure blood sample for creatinine measurement) deprived of patients with protocol deviations/violations. | Posted | Number | Number of patients | Baseline pre MRI and 3 days post MRI |
|
|
|
|
| Secondary | 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. | Per protocol population. This population is comprised of the full analysis set population (i.e. all included patients with a pre and post-procedure blood sample for creatinine measurement) deprived of patients with protocol deviations/violations. | Posted | Mean | Standard Deviation | Percentage of change from baseline | Baseline pre MRI and 3 days post MRI |
|
|
|
|
| Secondary | 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. | Full analysis set population: all included patients with a pre and a post-procedure blood sample for creatinine measurements. | Posted | Mean | Standard Deviation | Percentage of change from baseline | Baseline pre MRI and 3 days post MRI |
|
|
|
|
| Secondary | 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. | Per protocol population: This population is comprised of the full analysis set population (i.e. all included patients with a pre and a post- procedure blood sample for creatinine measurements) deprived of patients with protocol deviations/violations. | Posted | Mean | Standard Deviation | Percentage of change from baseline | Baseline pre MRI and 3 days post MRI |
|
|
|
|
| 0 |
| 70 |
| 6 |
| 70 |
| EG001 | Non-enhanced MRI | non-enhanced MRI: non injected MRI | 0 | 44 | 0 | 44 |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment | This adverse event was deemed not related to the injection of Dotarem® |
|
| Hypotension | Vascular disorders | MedDRA 13.1 | Systematic Assessment | This adverse event was deemed not related to the injection of Dotarem® |
|
| Blood creatinin increased | Investigations | MedDRA 13.1 | Systematic Assessment | This adverse event was deemed possibly related to the injection of Dotarem® |
|
| toothache | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment | This adverse event was deemed not related to the injection of Dotarem® |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.1 | Systematic Assessment | This adverse event was deemed not related to the injection of Dotarem® |
|
No unpublished data given to the investigator may be transmitted to a third party without prior approval of the sponsor in writing. The data are the exclusive property of Guerbet.
The investigator undertakes to submit to Guerbet any draft articles or papers related to this study within 30 days of their submission to the scientific review or the congress scientific committee.
All written or oral papers and publications must have the joint agreement of the investigator and the sponsor.
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |