Chronic Kidney Disease
Conditions
Keywords
CKD, Paediatric, Darbepoetin Alfa
Brief summary
This European study observes paediatric patients with Chronic Kidney Disease using Darbepoetin Alfa to assess the drug's long term safety and profile the patterns of its use within this population.
Interventions
None listed
Sponsors
Amgen
Study design
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 16 Years
Healthy volunteers
No
Inclusion criteria
* Anaemia attributed to Chronic Kidney Disease (CKD) * Sixteen years of age or under * Documented CKD as demonstrated by estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73m² (Schwartz equation) for ≥3 months if not on dialysis, or: Receiving dialysis * Treatment with darbepoetin alfa * Documented informed consent by a parent or authorised individual, if required, and assent by the patient if appropriate
Exclusion criteria
* Active malignancy or current chemotherapy or radiation therapy * Investigator unlikely to be able to obtain adequate follow-up information, or participant will not be available for follow-up assessment * Currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study; subject receiving other investigational agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Drug Reactions (SADR), Serious Adverse Events (SAEs) or Events of Medical Interest (EMIs) | 2 years | An ADR was defined as an undesirable medical occurrence or worsening of a pre-existing medical condition that the investigator considered associated with the use of darbepoetin alfa. An AE is any untoward medical occurrence or worsening of a pre-existing condition whether or not considered to have a causal relationship with darbepoetin alfa. An SADR or SAE is any ADR or AE that is either: • Fatal • Life threatening • Requires or prolongs in-patient hospitalization • A persistent or significant disability/incapacity, or • A congenital anomaly/birth defect. An EMI is defined as one of the following pre-specified AEs: Thromboembolic Events (eg, venous thrombosis, embolism, vascular occlusion) • Seizures • Severe hypertension (Investigator discretion accompanied by recorded blood pressure) • Cardiovascular events (eg, cardiac arrhythmia, myocardial ischaemia/infarction, heart failure) • Pure red cell aplasia (PRCA) • Hypersensitivity reactions (eg, rash, urticaria, anaphylaxis). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin Concentration by Three Monthly Intervals | Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24 | — |
| Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Baseline and Months 1 to 24 | Baseline dose = the daily dose equivalent x 30, where the daily dose equivalent = the last available dose prior to or at Day 1 / reported intended frequency. |
| Parathyroid Hormone Level by Three Monthly Intervals | Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24 | — |
| Number of Participants With Non-serious Adverse Drug Reactions (ADRs) | 2 years | An ADR was defined as an undesirable medical occurrence or worsening of a pre-existing medical condition that the investigator considered associated with the use of darbepoetin alfa. A non-serious ADR was one in which none of the following applied: * Fatal * Life threatening * Required or prolonged in-patient hospitalization * A persistent or significant disability/incapacity, or * A congenital anomaly/birth defect. |
Participant flow
Recruitment details
First participant was enrolled on 26 February 2008; last participant was enrolled on 24 February 2011.
Participants by arm
| Arm | Count |
|---|---|
| Darbepoetin Alfa Participants with chronic kidney disease who received darbepoetin alfa for the treatment of anaemia as part of routine clinical practice. | 319 |
| Total | 319 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 6 |
| Overall Study | Ineligibility determined | 6 |
| Overall Study | Lost to Follow-up | 11 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Protocol-specified criteria | 142 |
| Overall Study | Requirement for alternative therapy | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Darbepoetin Alfa |
|---|---|
| Age, Continuous | 9.1 years STANDARD_DEVIATION 5 |
| Age, Customized ≥ 12 years | 133 participants |
| Age, Customized 1 to < 6 years | 83 participants |
| Age, Customized < 1 year | 13 participants |
| Age, Customized 6 to < 12 years | 90 participants |
| Race/Ethnicity, Customized Asian | 8 participants |
| Race/Ethnicity, Customized Black or African American | 9 participants |
| Race/Ethnicity, Customized Japanese | 0 participants |
| Race/Ethnicity, Customized Not recorded | 19 participants |
| Race/Ethnicity, Customized Other | 9 participants |
| Race/Ethnicity, Customized White or Caucasian | 274 participants |
| Sex: Female, Male Female | 142 Participants |
| Sex: Female, Male Male | 177 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 7 / 319 |
| serious Total, serious adverse events | 162 / 319 |
Outcome results
Primary
Number of Participants With Serious Adverse Drug Reactions (SADR), Serious Adverse Events (SAEs) or Events of Medical Interest (EMIs)
An ADR was defined as an undesirable medical occurrence or worsening of a pre-existing medical condition that the investigator considered associated with the use of darbepoetin alfa. An AE is any untoward medical occurrence or worsening of a pre-existing condition whether or not considered to have a causal relationship with darbepoetin alfa. An SADR or SAE is any ADR or AE that is either: • Fatal • Life threatening • Requires or prolongs in-patient hospitalization • A persistent or significant disability/incapacity, or • A congenital anomaly/birth defect. An EMI is defined as one of the following pre-specified AEs: Thromboembolic Events (eg, venous thrombosis, embolism, vascular occlusion) • Seizures • Severe hypertension (Investigator discretion accompanied by recorded blood pressure) • Cardiovascular events (eg, cardiac arrhythmia, myocardial ischaemia/infarction, heart failure) • Pure red cell aplasia (PRCA) • Hypersensitivity reactions (eg, rash, urticaria, anaphylaxis).
Time frame: 2 years
Population: Full Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Darbepoetin Alfa | Number of Participants With Serious Adverse Drug Reactions (SADR), Serious Adverse Events (SAEs) or Events of Medical Interest (EMIs) | Serious Adverse Drug Reactions | 4 participants |
| Darbepoetin Alfa | Number of Participants With Serious Adverse Drug Reactions (SADR), Serious Adverse Events (SAEs) or Events of Medical Interest (EMIs) | Serious Adverse Events | 162 participants |
| Darbepoetin Alfa | Number of Participants With Serious Adverse Drug Reactions (SADR), Serious Adverse Events (SAEs) or Events of Medical Interest (EMIs) | Events of Medical Interest | 39 participants |
Secondary
Hemoglobin Concentration by Three Monthly Intervals
Time frame: Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Baseline (n=308) | 11.06 g/dL | 95% Confidence Interval 1.62 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 3 (n=260) | 11.47 g/dL | 95% Confidence Interval 1.64 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 6 (n=269) | 11.34 g/dL | 95% Confidence Interval 1.32 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 9 (n=245) | 11.43 g/dL | 95% Confidence Interval 1.5 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 12 (n=214) | 11.39 g/dL | 95% Confidence Interval 1.38 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 15 (n=199) | 11.26 g/dL | 95% Confidence Interval 1.35 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 18 (n=167) | 11.30 g/dL | 95% Confidence Interval 1.5 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 21 (n=154) | 11.30 g/dL | 95% Confidence Interval 1.34 |
| Darbepoetin Alfa | Hemoglobin Concentration by Three Monthly Intervals | Month 24 (n=151) | 11.42 g/dL | 95% Confidence Interval 1.4 |
Secondary
Number of Participants With Non-serious Adverse Drug Reactions (ADRs)
An ADR was defined as an undesirable medical occurrence or worsening of a pre-existing medical condition that the investigator considered associated with the use of darbepoetin alfa. A non-serious ADR was one in which none of the following applied: * Fatal * Life threatening * Required or prolonged in-patient hospitalization * A persistent or significant disability/incapacity, or * A congenital anomaly/birth defect.
Time frame: 2 years
Population: Full analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Darbepoetin Alfa | Number of Participants With Non-serious Adverse Drug Reactions (ADRs) | 4 participants |
Secondary
Parathyroid Hormone Level by Three Monthly Intervals
Time frame: Baseline, Months 3, 6, 9, 12, 15, 18, 21, and 24
Population: Full analysis set
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Baseline (n=228) | 20.44 pmol/L | Inter-Quartile Range 1.62 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 3 (n=236) | 19.76 pmol/L | Inter-Quartile Range 1.64 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 6 (n=246) | 18.12 pmol/L | Inter-Quartile Range 1.32 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 9 (n=225) | 16.70 pmol/L | Inter-Quartile Range 1.5 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 12 (n=194) | 19.11 pmol/L | Inter-Quartile Range 1.38 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 15 (n=184) | 17.51 pmol/L | Inter-Quartile Range 1.35 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 18 (n=150) | 17.69 pmol/L | Inter-Quartile Range 1.5 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 21 (n=142) | 18.12 pmol/L | Inter-Quartile Range 1.34 |
| Darbepoetin Alfa | Parathyroid Hormone Level by Three Monthly Intervals | Month 24 (n=137) | 21.20 pmol/L | Inter-Quartile Range 1.4 |
Secondary
Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals
Baseline dose = the daily dose equivalent x 30, where the daily dose equivalent = the last available dose prior to or at Day 1 / reported intended frequency.
Time frame: Baseline and Months 1 to 24
Population: Full analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Baseline (n=273) | 1.99 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 1 (n=311) | 1.90 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 2 (n=304) | 1.91 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 3 (n=297) | 1.94 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 4 (n=287) | 1.87 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 5 (n=277) | 1.82 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 6 (n=269) | 1.87 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 7 (n=256) | 1.79 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 8 (n=245) | 1.79 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 9 (n=233) | 1.69 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 10 (n=227) | 1.63 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 11 (n=216) | 1.72 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 12 (n=211) | 1.66 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 13 (n=206) | 1.58 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 14 (n=200) | 1.65 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 15 (n=193) | 1.71 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 16 (n=186) | 1.71 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 17 (n=180) | 1.73 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 18 (n=170) | 1.71 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 19 (n=164) | 1.71 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 20 (n=162) | 1.70 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 21 (n=157) | 1.79 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 22 (n=155) | 1.70 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 23 (n=154) | 1.63 μg/kg/month |
| Darbepoetin Alfa | Weight Adjusted Darbepoetin Alfa Monthly Dose by Monthly Intervals | Month 24 (n=146) | 1.44 μg/kg/month |