Trial Outcomes & Findings for Safety and Efficacy Evaluation of DOTAREM® in MRI of Central Nervous System (CNS) Lesions (NCT NCT01211873)

NCT ID: NCT01211873

Last Updated: 2019-04-18

Results Overview

To demonstrate the superiority of combined unenhanced and Dotarem enhanced MRI (PAIRED) compared to unenhanced MRI (PRE) in terms of lesion visualization. Unenhanced MRI refers to MRI before administration of contrast agent. Enhanced MRI refers to MRI after contrast agent injection. "Pre" refers to unenhanced MRI. "PAIRED" refer to combined unenhanced and enhanced MRI. The measure used a specific scale with 3-point levels to assess lesion visualization. At lesion level, the scale range is from 0 through 1 to 2. Score 0 means a worse outcome and score 2 means a better outcome. Patient score is the sum of all lesion scores. Up to 5 of the largest representative lesions were assessed. At patient level, the maximum score is 10, minimum score is 0.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 416 participants
• Primary outcome timeframe: up to 24 hours
• Results posted on: 2019-04-18

Participant Flow

First patient First Visit : 16 Sept 2010 Last patient Last Visit : 16 Nov 2011 Locations: radiology departments

Any patient who did not fulfill eligibility criteria was not randomized / assigned to a treatment group.

Participant milestones

Measure	Dotarem (Gadoterate Meglumine) Dotarem and Magnevist were randomised as 2:1 ratio for adult patients.	Magnevist (Gadopentetate Dimeglumine) Dotarem and Magnevist were randomised as 2:1 ratio	Dotarem 2 (Gadoterate Meglumine) Pediatric patients were assigned to Dotarem group only
Overall Study STARTED	245	119	38
Overall Study COMPLETED	240	117	36
Overall Study NOT COMPLETED	5	2	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Evaluation of DOTAREM® in MRI of Central Nervous System (CNS) Lesions

Baseline characteristics by cohort

Measure	Magnevist (Gadopentetate Dimeglumine) n=119 Participants adults received Magnevist as 1:2 ratio compared to Dotarem	Dotarem (Gadoterate Meglumine) n=245 Participants adults received Dotarem as 2:1 ratio compared to Magnevist.	Dotarem 2 (Gadoterate Meglumine) n=38 Participants All children were assigned to Dotarem	Total n=402 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	38 Participants n=5 Participants	38 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	89 Participants n=5 Participants	185 Participants n=7 Participants	0 Participants n=5 Participants	274 Participants n=4 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants	60 Participants n=7 Participants	0 Participants n=5 Participants	90 Participants n=4 Participants
Age, Continuous	55.95 years STANDARD_DEVIATION 14.43 • n=5 Participants	53.17 years STANDARD_DEVIATION 14.35 • n=7 Participants	9.29 years STANDARD_DEVIATION 4.49 • n=5 Participants	49.8 years STANDARD_DEVIATION 19.0 • n=4 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	131 Participants n=7 Participants	22 Participants n=5 Participants	218 Participants n=4 Participants
Sex: Female, Male Male	54 Participants n=5 Participants	114 Participants n=7 Participants	16 Participants n=5 Participants	184 Participants n=4 Participants
Region of Enrollment United States	30 participants n=5 Participants	65 participants n=7 Participants	17 participants n=5 Participants	112 participants n=4 Participants
Region of Enrollment France	13 participants n=5 Participants	30 participants n=7 Participants	0 participants n=5 Participants	43 participants n=4 Participants
Region of Enrollment Argentina	12 participants n=5 Participants	22 participants n=7 Participants	14 participants n=5 Participants	48 participants n=4 Participants
Region of Enrollment Brazil	5 participants n=5 Participants	8 participants n=7 Participants	4 participants n=5 Participants	17 participants n=4 Participants
Region of Enrollment Spain	2 participants n=5 Participants	8 participants n=7 Participants	0 participants n=5 Participants	10 participants n=4 Participants
Region of Enrollment Austria	10 participants n=5 Participants	20 participants n=7 Participants	0 participants n=5 Participants	30 participants n=4 Participants
Region of Enrollment Chile	3 participants n=5 Participants	5 participants n=7 Participants	3 participants n=5 Participants	11 participants n=4 Participants
Region of Enrollment Germany	20 participants n=5 Participants	40 participants n=7 Participants	0 participants n=5 Participants	60 participants n=4 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants	6 participants n=7 Participants	0 participants n=5 Participants	9 participants n=4 Participants
Region of Enrollment Italy	7 participants n=5 Participants	15 participants n=7 Participants	0 participants n=5 Participants	22 participants n=4 Participants
Region of Enrollment Korea, Republic of	14 participants n=5 Participants	26 participants n=7 Participants	0 participants n=5 Participants	40 participants n=4 Participants

PRIMARY outcome

Timeframe: up to 24 hours

Population: The primary analysis was performed at the patient level using off-site readings by 3 readers. The number of participants for analysis depended on the number of evaluable cases (PRE and PAIRED) determined by each reader. Only adult participants were included in this data set.

To demonstrate the superiority of combined unenhanced and Dotarem enhanced MRI (PAIRED) compared to unenhanced MRI (PRE) in terms of lesion visualization.

Unenhanced MRI refers to MRI before administration of contrast agent. Enhanced MRI refers to MRI after contrast agent injection. "Pre" refers to unenhanced MRI. "PAIRED" refer to combined unenhanced and enhanced MRI.

The measure used a specific scale with 3-point levels to assess lesion visualization. At lesion level, the scale range is from 0 through 1 to 2. Score 0 means a worse outcome and score 2 means a better outcome. Patient score is the sum of all lesion scores. Up to 5 of the largest representative lesions were assessed. At patient level, the maximum score is 10, minimum score is 0.

Outcome measures

Measure	Dotarem (Gadoterate Meglumine) - PRE n=224 Participants Any sequence acquired prior to injection of Dotarem was pooled as PRE	Dotarem (Gadoterate Meglumine) - PAIRED n=235 Participants All sequences pre- and post-injection of Dotarem were pooled as PAIRED	Magnevist (Gadopentetate Dimeglumine) - PRE Any sequence acquired prior to injection of Magnevist was pooled as PRE	Magnevist (Gadopentetate Dimeglumine) - PAIRED All sequences pre- and post-injection of Magnevist were pooled as PAIRED
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Border Delineation Blinded Reader 1	1.06 units on a scale Standard Deviation 1.23	3.30 units on a scale Standard Deviation 2.64	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Internal Morphology Blinded Reader 2	1.76 units on a scale Standard Deviation 1.24	4.49 units on a scale Standard Deviation 2.93	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Internal Morphology Blinded Reader 3	1.45 units on a scale Standard Deviation 1.13	2.93 units on a scale Standard Deviation 2.30	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Border Delineation Blinded Reader 2	1.62 units on a scale Standard Deviation 1.43	4.49 units on a scale Standard Deviation 2.94	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Border Delineation Blinded Reader 3	1.43 units on a scale Standard Deviation 1.29	2.54 units on a scale Standard Deviation 2.30	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Internal Morphology Blinded Reader 1	0.97 units on a scale Standard Deviation 1.05	3.70 units on a scale Standard Deviation 2.63	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Contrast Enhancement Blinded Reader 1	0.01 units on a scale Standard Deviation 0.20	3.11 units on a scale Standard Deviation 2.52	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Contrast Enhancement Blinded Reader 2	0.01 units on a scale Standard Deviation 0.15	3.73 units on a scale Standard Deviation 2.67	—	—
MRI Lesion Visualization (Border Delineation, Internal Morphology and Contrast Enhancement) at Patient Level for Both "Pre" and "Paired" Evaluation Contrast Enhancement Blinded Reader 3	0.01 units on a scale Standard Deviation 0.13	2.95 units on a scale Standard Deviation 2.44	—	—

SECONDARY outcome

Timeframe: up to 24 hours

Population: The number of participants for analysis depended on the number of evaluable cases (PRE and PAIRED) determined by each reader. Only adult participants are included in this data set.

Image quality was evaluated for each lesion according to a 3-point scale with the following grades; poor (1), fair (2) or good (3), and an overall score per patient was calculated. At patient level, the maximum score is 3, minimum score is 1. Higher scores mean a better image quality.

Outcome measures

Measure	Dotarem (Gadoterate Meglumine) - PRE n=224 Participants Any sequence acquired prior to injection of Dotarem was pooled as PRE	Dotarem (Gadoterate Meglumine) - PAIRED n=235 Participants All sequences pre- and post-injection of Dotarem were pooled as PAIRED	Magnevist (Gadopentetate Dimeglumine) - PRE n=113 Participants Any sequence acquired prior to injection of Magnevist was pooled as PRE	Magnevist (Gadopentetate Dimeglumine) - PAIRED n=116 Participants All sequences pre- and post-injection of Magnevist were pooled as PAIRED
Image Quality Score Reader 1	1.41 units on a scale Standard Deviation 0.52	2.98 units on a scale Standard Deviation 0.20	1.42 units on a scale Standard Deviation 0.53	2.96 units on a scale Standard Deviation 0.26
Image Quality Score Reader 2	1.72 units on a scale Standard Deviation 0.45	3.00 units on a scale Standard Deviation 0	1.74 units on a scale Standard Deviation 0.44	2.98 units on a scale Standard Deviation 0.19
Image Quality Score Reader 3	2.00 units on a scale Standard Deviation 0.07	2.99 units on a scale Standard Deviation 0.11	1.99 units on a scale Standard Deviation 0.09	2.99 units on a scale Standard Deviation 0.09

SECONDARY outcome

Timeframe: up to 24 hours

Population: The number of participants for analysis depended on the number of evaluable cases (PRE and PAIRED) determined by each reader. Only adult participants are included in this data set.

Level of diagnostic confidence when evaluating the MRI modalities was graded using a 5-point scale as nil (1), poor (2), moderate (3), high (4) and excellent (5).

Outcome measures

Measure	Dotarem (Gadoterate Meglumine) - PRE n=224 Participants Any sequence acquired prior to injection of Dotarem was pooled as PRE	Dotarem (Gadoterate Meglumine) - PAIRED n=235 Participants All sequences pre- and post-injection of Dotarem were pooled as PAIRED	Magnevist (Gadopentetate Dimeglumine) - PRE n=113 Participants Any sequence acquired prior to injection of Magnevist was pooled as PRE	Magnevist (Gadopentetate Dimeglumine) - PAIRED n=116 Participants All sequences pre- and post-injection of Magnevist were pooled as PAIRED
Diagnostic Confidence Score Reader 2	2.84 units on a scale Standard Deviation 0.61	4.89 units on a scale Standard Deviation 0.31	2.85 units on a scale Standard Deviation 0.59	4.92 units on a scale Standard Deviation 0.36
Diagnostic Confidence Score Reader 1	3.04 units on a scale Standard Deviation 0.90	4.59 units on a scale Standard Deviation 0.64	3.11 units on a scale Standard Deviation 0.86	4.66 units on a scale Standard Deviation 0.64
Diagnostic Confidence Score Reader 3	3.47 units on a scale Standard Deviation 1.22	4.41 units on a scale Standard Deviation 0.98	3.59 units on a scale Standard Deviation 1.29	4.59 units on a scale Standard Deviation 0.81

SECONDARY outcome

Timeframe: up to 24 hours

Population: The number of participants for analysis depended on the number of evaluable cases (PRE and PAIRED) determined by each reader. Only adult participants are included in this data set.

The number of lesions for which observations could be made was calculated for each MRI modality and results are summarized per patient

Outcome measures

Measure	Dotarem (Gadoterate Meglumine) - PRE n=224 Participants Any sequence acquired prior to injection of Dotarem was pooled as PRE	Dotarem (Gadoterate Meglumine) - PAIRED n=235 Participants All sequences pre- and post-injection of Dotarem were pooled as PAIRED	Magnevist (Gadopentetate Dimeglumine) - PRE n=113 Participants Any sequence acquired prior to injection of Magnevist was pooled as PRE	Magnevist (Gadopentetate Dimeglumine) - PAIRED n=116 Participants All sequences pre- and post-injection of Magnevist were pooled as PAIRED
Number of Lesions Reader 1	1.97 Number of lesions Standard Deviation 3.16	2.69 Number of lesions Standard Deviation 4.71	1.98 Number of lesions Standard Deviation 3.85	4.19 Number of lesions Standard Deviation 10.54
Number of Lesions Reader 2	2.29 Number of lesions Standard Deviation 3.69	3.16 Number of lesions Standard Deviation 5.21	2.60 Number of lesions Standard Deviation 5.42	4.50 Number of lesions Standard Deviation 9.95
Number of Lesions Reader 3	1.97 Number of lesions Standard Deviation 2.99	2.46 Number of lesions Standard Deviation 4.53	2.15 Number of lesions Standard Deviation 3.97	3.97 Number of lesions Standard Deviation 10.02

Adverse Events

Dotarem (Gadoterate Meglumine )

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Magnevist (Gadopentetate Dimeglumine)

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Dotarem 2 (Gadoterate Meglumine )

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dotarem (Gadoterate Meglumine ) n=240 participants at risk Dotarem and Magnevist were randomised as 2:1 ratio for adults	Magnevist (Gadopentetate Dimeglumine) n=117 participants at risk Dotarem and Magnevist were randomised as 2:1 ratio	Dotarem 2 (Gadoterate Meglumine ) n=38 participants at risk children were only assigned to Dotarem
Gastrointestinal disorders small intestine perforation	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.85% 1/117 • Number of events 1 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Respiratory, thoracic and mediastinal disorders hypoxia	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Number of events 1 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Nervous system disorders neurological decompensation	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Number of events 1 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.

Other adverse events

Measure	Dotarem (Gadoterate Meglumine ) n=240 participants at risk Dotarem and Magnevist were randomised as 2:1 ratio for adults	Magnevist (Gadopentetate Dimeglumine) n=117 participants at risk Dotarem and Magnevist were randomised as 2:1 ratio	Dotarem 2 (Gadoterate Meglumine ) n=38 participants at risk children were only assigned to Dotarem
General disorders injection site pain	1.2% 3/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.85% 1/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
General disorders injection site hematoma	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 3/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
General disorders extravasation	0.42% 1/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	1.7% 2/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
General disorders chest pain	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	1.7% 2/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Investigations blood urine present	0.83% 2/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Gastrointestinal disorders nausea	1.2% 3/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Nervous system disorders headache	0.42% 1/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.85% 1/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	5.3% 2/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Nervous system disorders dizziness	0.42% 1/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Gastrointestinal disorders vomiting	0.42% 1/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
General disorders asthenia	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
General disorders application site erythema	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Respiratory, thoracic and mediastinal disorders hypoxia	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.
Skin and subcutaneous tissue disorders pruritus	0.00% 0/240 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	0.00% 0/117 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.	2.6% 1/38 • Adverse events were collected from patient consent signature to the end of the last visits, maximum duration is 29 days. Participants at risk were subjects exposed to contrast agent administration. In Dotarem group, 240 adults were injected, Dotarem group 2, 38 children were injected (2 children were withdrawn after agent administration) and in Magnevist group, 117 adults were injected.

Additional Information

Jing Hao, MD

Guerbet

Phone: +33145915000

Email: jing.hao@guerbet.com

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