Trial Outcomes & Findings for Renal Safety Evaluation After Dotarem®-Enhanced MRI (NCT NCT00650845)

NCT ID: NCT00650845

Last Updated: 2015-06-09

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

135 participants

Primary outcome timeframe

baseline pre MRI and 3 days post MRI

Results posted on

2015-06-09

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure
Dotarem®-Enhanced MRI
Dotarem®: Single IV administration
Non-enhanced MRI
non-enhanced MRI: non injected MRI
Overall Study
STARTED
75
57
Overall Study
COMPLETED
70
44
Overall Study
NOT COMPLETED
5
13

Reasons for withdrawal

Reasons for withdrawal
Measure
Dotarem®-Enhanced MRI
Dotarem®: Single IV administration
Non-enhanced MRI
non-enhanced MRI: non injected MRI
Overall Study
Withdrawal by Subject
5
0
Overall Study
Protocol Violation
0
13

Baseline Characteristics

Renal Safety Evaluation After Dotarem®-Enhanced MRI

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Dotarem®-Enhanced MRI
n=75 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=57 Participants
non-enhanced MRI: non injected MRI
Total
n=132 Participants
Total of all reporting groups
Age, Continuous
69.6 years
STANDARD_DEVIATION 11.5 • n=5 Participants
66.2 years
STANDARD_DEVIATION 12.2 • n=7 Participants
67.9 years
STANDARD_DEVIATION 12.0 • n=5 Participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
24 Participants
n=5 Participants
20 Participants
n=7 Participants
44 Participants
n=5 Participants
Age, Categorical
>=65 years
51 Participants
n=5 Participants
37 Participants
n=7 Participants
88 Participants
n=5 Participants
Sex: Female, Male
Female
24 Participants
n=5 Participants
23 Participants
n=7 Participants
47 Participants
n=5 Participants
Sex: Female, Male
Male
51 Participants
n=5 Participants
34 Participants
n=7 Participants
85 Participants
n=5 Participants
Region of Enrollment
France
44 participants
n=5 Participants
11 participants
n=7 Participants
55 participants
n=5 Participants
Region of Enrollment
Belgium
14 participants
n=5 Participants
7 participants
n=7 Participants
21 participants
n=5 Participants
Region of Enrollment
Spain
17 participants
n=5 Participants
23 participants
n=7 Participants
40 participants
n=5 Participants
Region of Enrollment
Italy
0 participants
n=5 Participants
16 participants
n=7 Participants
16 participants
n=5 Participants

PRIMARY outcome

Timeframe: baseline pre MRI and 3 days post MRI

Population: Full analysis set population: all included patients with a pre and post-procedure blood sample for creatinine measures.

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.

Outcome measures

Outcome measures
Measure
Dotarem®-Enhanced MRI
n=70 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=44 Participants
non-enhanced MRI: non injected MRI
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.
1 Number of patients
0 Number of patients

PRIMARY outcome

Timeframe: Baseline pre MRI and 3 days post MRI

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dotarem®-Enhanced MRI
n=37 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=30 Participants
non-enhanced MRI: non injected 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.
1 Number of patients
0 Number of patients

SECONDARY outcome

Timeframe: Baseline pre MRI and 3 days post MRI

Population: Full analysis set population:all included patients with a pre and post-procedure blood sample for creatinine measurement.

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.

Outcome measures

Outcome measures
Measure
Dotarem®-Enhanced MRI
n=70 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=44 Participants
non-enhanced MRI: non injected MRI
Percent Change of Serum Creatinine Level From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population.
-1.40 Percentage of change from baseline
Standard Deviation 10.36
-3.48 Percentage of change from baseline
Standard Deviation 9.92

SECONDARY outcome

Timeframe: Baseline pre MRI and 3 days post MRI

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dotarem®-Enhanced MRI
n=37 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=30 Participants
non-enhanced MRI: non injected MRI
Percent Change of Serum Creatinine Level Variation From Baseline to 72±24 Hours After Examination, in the Per Protocol Population
0.05 Percentage of change from baseline
Standard Deviation 10.84
-5.17 Percentage of change from baseline
Standard Deviation 9.16

SECONDARY outcome

Timeframe: Baseline pre MRI and 3 days post MRI

Population: Full analysis set population: all included patients with a pre and a post-procedure blood sample for creatinine measurements.

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.

Outcome measures

Outcome measures
Measure
Dotarem®-Enhanced MRI
n=70 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=44 Participants
non-enhanced MRI: non injected MRI
Percent Change of Estimated Glomerular Filtration Rate (eGFR) Values From Baseline to 72±24 Hours After Examination, in the Full Analysis Set Population
3.02 Percentage of change from baseline
Standard Deviation 12.51
5.55 Percentage of change from baseline
Standard Deviation 12.94

SECONDARY outcome

Timeframe: Baseline pre MRI and 3 days post MRI

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Dotarem®-Enhanced MRI
n=37 Participants
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=30 Participants
non-enhanced MRI: non injected MRI
eGFR Values Variation Between Baseline and 72±24 Hours After Examination, in the Per Protocol Population
1.37 Percentage of change from baseline
Standard Deviation 12.65
7.58 Percentage of change from baseline
Standard Deviation 12.82

Adverse Events

Dotarem®-Enhanced MRI

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Non-enhanced MRI

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Dotarem®-Enhanced MRI
n=70 participants at risk
Dotarem®: Single IV administration before the MRI
Non-enhanced MRI
n=44 participants at risk
non-enhanced MRI: non injected MRI
Vascular disorders
Hematoma
1.4%
1/70 • Number of events 1 • 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.
0.00%
0/44 • 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.
Gastrointestinal disorders
Abdominal pain upper
1.4%
1/70 • Number of events 1 • 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.
0.00%
0/44 • 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.
Vascular disorders
Hypotension
1.4%
1/70 • Number of events 1 • 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.
0.00%
0/44 • 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.
Investigations
Blood creatinin increased
1.4%
1/70 • Number of events 1 • 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.
0.00%
0/44 • 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.
Gastrointestinal disorders
toothache
1.4%
1/70 • Number of events 1 • 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.
0.00%
0/44 • 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.
Gastrointestinal disorders
Constipation
1.4%
1/70 • Number of events 1 • 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.
0.00%
0/44 • 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.

Additional Information

Pierre Desché, MD - VP Development, Medical and Regulatory Affairs.

Guerbet

Phone: +33 1 45 91 50 00

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER