Trial Outcomes & Findings for Safety and Dialysability of Dotarem® in Dialysed Patients (NCT NCT01449266)

Last Updated: 2015-07-08

Results Overview

To evaluate the decrease in seric concentration of gadolinium, after each hemodialysis session of patients injected with 0.1 mmol/kg of Dotarem® . The percent change of gadolinium concentration is calculated by estimating the amount of serum gadolinium before and after each hemodialysis session. Calculations are performed only for subjects with concentration above the lower limit of quantification (LLQ)

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

Dotarem® dialysability assessed up to 4 days after Dotarem® administration

Results posted on

2015-07-08

Participant Flow

Participant milestones

Participant milestones
Measure	Dotarem® Injected Patients Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol) Dotarem®: Dotarem® was administered at a dose of 0.1 mmoL/kg (0.2 mL/kg).
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Dialysability of Dotarem® in Dialysed Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dotarem®-Injected Patients n=10 Participants Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol) Dotarem®: Dotarem® was administered at a dose of 0.1 mmoL/kg (0.2 mL/kg).
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=99 Participants
Age, Categorical >=65 years	5 Participants n=99 Participants
Age, Continuous	64.0 years n=99 Participants
Sex: Female, Male Female	5 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants
Region of Enrollment Belgium	10 participants n=99 Participants

PRIMARY outcome

Timeframe: Dotarem® dialysability assessed up to 4 days after Dotarem® administration

Population: After second hemodialysis, 3 subjects had Gd concentration\<LLQ and are not included in the analysis; after third hemodialysis, 8 subjects had Gd concentration\<LLQ and are not included in the analysis

Outcome measures

Outcome measures
Measure	Dotarem® Injected Patients n=10 Participants Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol)
Dialysability of Dotarem® in Dialysed Patients Percent change at 0.5h after first hemodialysis	-88.2 percent change in Gd concentration Interval -93.5 to -84.7
Dialysability of Dotarem® in Dialysed Patients Percent change at 1.5h after first hemodialysis	-93.4 percent change in Gd concentration Interval -95.7 to -90.3
Dialysability of Dotarem® in Dialysed Patients Percent change at 4h after first hemodialysis	-97.1 percent change in Gd concentration Interval -99.1 to -90.5
Dialysability of Dotarem® in Dialysed Patients Percent change at 4h after second hemodialysis n=7	-94.8 percent change in Gd concentration Interval -97.7 to -84.8
Dialysability of Dotarem® in Dialysed Patients Percent change at 4h after third hemodialysis n=2	-89.9 percent change in Gd concentration Interval -94.9 to -85.0

SECONDARY outcome

Timeframe: Safety assessed from patients inclusion until the last follow-up visit 3 months after Dotarem® administration

To evaluate the biological and clinical safety of Dotarem® by assessing vital signs, biological parameters, injection-site tolerance, through a 4-day post injection follow-up, adverse events through a 3-week post injection period and serious adverse events through a 3-month post injection period.

Outcome measures

Outcome measures
Measure	Dotarem® Injected Patients n=10 Participants Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol)
Safety of Dotarem® in Dialysed Patients Evaluated by the Number of Patients Experiencing Adverse Events.	8 participants

POST_HOC outcome

Timeframe: Dotarem® dialysability assessed 4h after second hemodialysis session which took place 2 days after Dotarem® administration

Population: 3 subjects had a gadolinium concentration \<LLQ after the second hemodialysis session

Evaluation of the decrease in seric concentration of gadolinium, 4h after the second hemodialysis session of patients injected with 0.1 mmol/kg of Dotarem®. The percent change of gadolinium concentration was estimated from the concentration of gadolinium after Dotarem® injection. Only subjects with gadolinium concentration above the lower limit of quantification (LLQ) were kept for analysis.

Outcome measures

Outcome measures
Measure	Dotarem® Injected Patients n=7 Participants Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol)
Percent Change in Gadolinium Serum Concentration 4h After Second Hemodialysis Session, Estimated From Subjects With Concentration Data Above the Limit of Detection	-99.5 Percent change in Gd concentration Interval -99.8 to -98.6

POST_HOC outcome

Timeframe: Dotarem® dialysability assessed 4h after third hemodialysis session which took place 4 days after Dotarem® administration

Population: 8 subjects had a gadolinium concentration \<LLQ after third hemodialysis session

The evaluation of the decrease in seric concentration of gadolinium, 4h after the third hemodialysis session of patients injected with 0.1 mmol/kg of Dotarem®. The percent change of gadolinium concentration was estimated from the concentration of gadolinium after Dotarem® injection. Only subjects with gadolinium concentration above the lower limit of detection were kept for analysis.

Outcome measures

Outcome measures
Measure	Dotarem® Injected Patients n=2 Participants Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol)
Percent Change in Gadolinium Serum Concentration 4h After Third Hemodialysis Session, Estimated From Subjects With Concentration Data Above the Limit of Detection	-99.7 percent change in Gd concentration Interval -99.8 to -99.7

Adverse Events

Dotarem® Injected Patients

Serious events: 4 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Dotarem® Injected Patients n=10 participants at risk Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol) Dotarem: Dotarem® was administered at a single dose of 0.1 mmoL/kg (0.2 mL/kg).
Infections and infestations moderate sepsis	20.0% 2/10 • Number of events 2 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Respiratory, thoracic and mediastinal disorders severe respiratory failure	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Vascular disorders severe peripheral ischemia	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Blood and lymphatic system disorders moderate thrombocytopenia	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Infections and infestations severe urosepsis	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Surgical and medical procedures Dialysis device insertion	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Surgical and medical procedures Nephrectomy	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.

Other adverse events

Other adverse events
Measure	Dotarem® Injected Patients n=10 participants at risk Male or female, aged ≥18 years • Subjects suffering from end-stage renal failure who require hemodialysis treatment for 3 times per week (or equivalent to allow overnight dialysis being rescheduled as appropriate per protocol) Dotarem: Dotarem® was administered at a single dose of 0.1 mmoL/kg (0.2 mL/kg).
Vascular disorders Hypotension	50.0% 5/10 • Number of events 5 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Nervous system disorders Headache	30.0% 3/10 • Number of events 3 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Muscle spasms	30.0% 3/10 • Number of events 3 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Blood and lymphatic system disorders Anemia	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Gastrointestinal disorders Abdominal pain	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
General disorders influenza-like illness	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
General disorders thirst	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Injury, poisoning and procedural complications Procedural pain	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Arthralgia	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Nervous system disorders Dizziness postural	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Nervous system disorders Presyncope	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.
Vascular disorders Hypertension	10.0% 1/10 • Number of events 1 • Safety assessment was performed at the day 1, day 2, and day 4 after Dotarem® injection. Two safety follow-up visits were performed at 3 weeks (+/- 2 days) and at 3 months (+/- 4 days) after Dotarem® injection. Adverse events (AEs) were followed from the subject's screening to the first safety follow-up visit (3 weeks +/- 2 days after the Dotarem® injection). At the second safety follow-up visit (3 months +/- 4 days after the Dotarem® injection), only Serious Adverse Events (SAEs) were evaluated.

Additional Information

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

Guerbet

Phone: +33 1 45 91 50 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No unpublished data given to the investigator may be transmitted to a third party without approval by the sponsor. The data are the exclusive property of Guerbet. The investigator undertakes to submit to Guerbet any articles or papers related to this study within 30 days of their submission to journals or congresses. All publications must have the joint agreement of the investigator and the sponsor. The investigator remains independent with no relationship of subordination with Guerbet.
Publication restrictions are in place

Restriction type: OTHER