End-stage Renal Failure
Conditions
Keywords
Dotarem, Dialyses, Dialysed, Safety, Safety and dialysability of Dotarem in dialysed patients
Brief summary
To evaluate the dialysability of Dotarem®, after an IV injection of 0.1 mmol/kg in patients with chronic renal failure who require hemodialysis treatment.
Detailed description
Ten adult patients suffering from end stage renal failure and requiring hemodialysis treatment for 3 times were enrolled. Patients received a single dose of Dotarem® at 0.1 mmol/kg before being submitted to hemodialysis to assess the dialysability of Dotarem® . After injection of Dotarem®, 3 sessions of hemodialysis were performed as follows: The first hemodialysis session started between 1 to 2 h after the injection; The second hemodialysis session occurred 2 days (i.e., 48 ± 2 h) after the Dotarem® injection; The third hemodialysis session occurred 4 days (i.e., 96 ± 4 h) after the Dotarem® injection. The decrease in serum Dotarem® concentration was assessed after each hemodialysis session. Safety assessments included adverse events (AEs), vital signs, injection-site tolerance, and laboratory assessments.Two safety follow-up visits were performed: one 3 weeks (± 2 days) and one 3 months (± 4 days) after the Dotarem® injection.
Interventions
DRUGDotarem® IV injection at 0.1 mmol/kg
Dotarem® was IV administered at a dose of 0.1 mmoL/kg (0.2 mL/kg).
Sponsors
Guerbet
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
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) * Female Subjects with effective contraception (contraceptive pill or Intra-Uterine Device), or surgically sterilized or post-menopausal (minimum 12 months amenorrhea) * Subjects having provided their written informed consent to participate in the trial
Exclusion criteria
* Known allergy to gadolinium chelates * Pregnant, breast feeding, or planning to become pregnant during the trial * Having received or scheduled to be injected with any contrast agent within 7 days before or after the Dotarem® injection * Schedule to receive erythropoietin (EPO) or iron therapy during 1 week after the Dotarem® injection * Evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Evidence of hepatitis C and/or positive hepatitis C antibody and/or positive hepatitis B surface antigen * History of hypersensitivity to drugs with a similar chemical structure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dialysability of Dotarem® in Dialysed Patients | Dotarem® dialysability assessed up to 4 days after Dotarem® administration | 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) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Dotarem® in Dialysed Patients Evaluated by the Number of Patients Experiencing Adverse Events. | 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. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Dotarem®-Injected Patients |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 64.0 years |
| Region of Enrollment Belgium | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 10 |
| serious Total, serious adverse events | 4 / 10 |
Outcome results
Primary
Dialysability of Dotarem® in Dialysed Patients
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)
Time frame: 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
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Dotarem® Injected Patients | Dialysability of Dotarem® in Dialysed Patients | Percent change at 1.5h after first hemodialysis | -93.4 percent change in Gd concentration |
| Dotarem® Injected Patients | Dialysability of Dotarem® in Dialysed Patients | Percent change at 0.5h after first hemodialysis | -88.2 percent change in Gd concentration |
| Dotarem® Injected Patients | Dialysability of Dotarem® in Dialysed Patients | Percent change at 4h after first hemodialysis | -97.1 percent change in Gd concentration |
| Dotarem® Injected Patients | Dialysability of Dotarem® in Dialysed Patients | Percent change at 4h after second hemodialysis n=7 | -94.8 percent change in Gd concentration |
| Dotarem® Injected Patients | Dialysability of Dotarem® in Dialysed Patients | Percent change at 4h after third hemodialysis n=2 | -89.9 percent change in Gd concentration |
Secondary
Safety of Dotarem® in Dialysed Patients Evaluated by the Number of Patients Experiencing Adverse Events.
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.
Time frame: Safety assessed from patients inclusion until the last follow-up visit 3 months after Dotarem® administration
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dotarem® Injected Patients | Safety of Dotarem® in Dialysed Patients Evaluated by the Number of Patients Experiencing Adverse Events. | 8 participants |
Post Hoc
Percent Change in Gadolinium Serum Concentration 4h After Second Hemodialysis Session, Estimated From Subjects With Concentration Data Above the Limit of Detection
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.
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dotarem® Injected Patients | 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 |
Post Hoc
Percent Change in Gadolinium Serum Concentration 4h After Third Hemodialysis Session, Estimated From Subjects With Concentration Data Above the Limit of Detection
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.
Time frame: 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
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Dotarem® Injected Patients | 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 |