Anemia
Conditions
Keywords
CKD, Darbepoetin Alfa, Dialysis, Hemodialysis, Anemia, Peg epoetin beta
Brief summary
To describe the time course of hemoglobin concentration in EU hemodialysis patients switched from methoxy polyethylene glycol-epoetin beta (PEG epoetin beta; Mircera) to darbepoetin alfa (Aranesp).
Detailed description
This is a multi-centre, observational cohort study of EU hemodialysis patients whose erythropoiesis stimulating agent (ESA) therapy has been switched from PEG epoetin beta to darbepoetin alfa. Data will be collected for the period spanning 14 weeks prior to switch through to 26 weeks post-switch.
Interventions
None listed
Sponsors
Amgen
Study design
Observational model
COHORT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients \>18 years of age. CKD diagnosis, receiving hemodialysis * Received PEG epoetin beta for 14weeks prior to switching to darbepoetin alfa and received at least one dose of darbepoetin alfa.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin Concentration at Monthly Intervals | Month -3, -2, -1 (pre-switch), and Month 1, 2, 3, 4, 5 and 6 (post-switch) | Hemoglobin concentration from 3 months prior to switch to darbepoetin alfa until the end of the observation period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch | Month -3, Month -2, Month -1 | Mean weekly doses were calculated per participant by first calculating a mean daily dose for the interval (by dividing each dose evenly between the days bounded by its date of administration and the day before the next dose, then taking a mean of these partial doses for the days in the interval) and multiplying by 7 to convert to a weekly dose. Weekly doses \>150 μg have been excluded as they were deemed infeasible values derived by the algorithm. |
| Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 1, 2, 3, 4, 5 and 6 | Mean weekly doses were calculated per participant by first calculating a mean daily dose for the interval (by dividing each dose evenly between the days bounded by its date of administration and the day before the next dose, then taking a mean of these partial doses for the days in the interval) and multiplying by 7 to convert to a weekly dose. Weekly doses \>150 μg have been excluded as they were deemed infeasible values derived by the algorithm. |
| Dose Ratio Measured at the Time of Switch From PEG Epoetin Beta to Darbepoetin Alfa | Week -1 and Week 1 | Dose ratio is the average weekly dose of the first darbepoetin alfa dose divided by the average weekly dose of peg-epoetin beta at switch (μg darbepoetin alfa per 1 μg pegylated-epoetin beta). |
| Hemoglobin Concentration Rate of Change by Period | Thre months prior to switch and 6 months after the switch | The hemoglobin rate of change is the maximum monthly increase and maximum monthly decrease for the pre- and post-switch periods. Within each period, the difference was calculated between each hemoglobin value and the most recent hemoglobin value taken at least 28 days previously. The rate of change was calculated by dividing this difference by the number of days in the interval and multiplying by 28. The maximum and minimum rate of change was then determined per participant. |
| Percentage of Participants With Hemoglobin Excursions | Month -3, -2, -1, 1, 2, 3, 4, 5 and 6 | The percentage of participants with at least one hemoglobin excursion, defined as hemoglobin concentrations below 10.0 g/dL and above 12.0 g/dL during the pre- and post-switch periods. |
Countries
Belgium, France, Germany, Greece, Netherlands, Spain, Switzerland
Participant flow
Recruitment details
First patient enrolled 28 August 2012; Last patient enrolled 3 July 2013.
Participants by arm
| Arm | Count |
|---|---|
| Chronic Kidney Disease (CKD) Participants with CKD on dialysis and treated with PEG epoetin beta immediately prior to being switched to darbepoetin alfa. | 785 |
| Total | 785 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 14 |
| Overall Study | Lost to Follow-up | 6 |
| Overall Study | Other | 3 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Renal transplant | 8 |
| Overall Study | Study completion data not recorded | 35 |
Baseline characteristics
| Characteristic | Chronic Kidney Disease (CKD) |
|---|---|
| Age, Continuous | 68.7 years STANDARD_DEVIATION 14.3 |
| Sex: Female, Male Female | 344 Participants |
| Sex: Female, Male Male | 441 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 987 | 1 / 987 |
| serious Total, serious adverse events | 0 / 987 | 0 / 987 |
Outcome results
Primary
Hemoglobin Concentration at Monthly Intervals
Hemoglobin concentration from 3 months prior to switch to darbepoetin alfa until the end of the observation period.
Time frame: Month -3, -2, -1 (pre-switch), and Month 1, 2, 3, 4, 5 and 6 (post-switch)
Population: Primary analysis set; participants with available data at each time point (indicated by n).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month -3 (n=725) | 11.27 g/dL | Standard Deviation 1.09 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month -2 (n=766) | 11.26 g/dL | Standard Deviation 1.08 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month -1 (n=769) | 11.19 g/dL | Standard Deviation 1.06 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month 1 (n=763) | 11.14 g/dL | Standard Deviation 1.09 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month 2 (n=755) | 11.36 g/dL | Standard Deviation 1.13 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month 3 (n=749) | 11.48 g/dL | Standard Deviation 1.14 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month 4 (n=754) | 11.38 g/dL | Standard Deviation 1.15 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month 5 (n=739) | 11.33 g/dL | Standard Deviation 1.15 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration at Monthly Intervals | Month 6 (n=742) | 11.29 g/dL | Standard Deviation 1.14 |
Secondary
Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period
Mean weekly doses were calculated per participant by first calculating a mean daily dose for the interval (by dividing each dose evenly between the days bounded by its date of administration and the day before the next dose, then taking a mean of these partial doses for the days in the interval) and multiplying by 7 to convert to a weekly dose. Weekly doses \>150 μg have been excluded as they were deemed infeasible values derived by the algorithm.
Time frame: Month 1, 2, 3, 4, 5 and 6
Population: Primary analysis set; participants with available data at each time point (as indicated by n).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Kidney Disease (CKD) | Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 1 (n=782) | 29.4 μg/week | 95% Confidence Interval 26.1 |
| Chronic Kidney Disease (CKD) | Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 2 (n=778) | 27.8 μg/week | 95% Confidence Interval 26 |
| Chronic Kidney Disease (CKD) | Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 3 (n=780) | 25.4 μg/week | 95% Confidence Interval 26.8 |
| Chronic Kidney Disease (CKD) | Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 4 (n=779) | 23.3 μg/week | 95% Confidence Interval 27.6 |
| Chronic Kidney Disease (CKD) | Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 5 (n=777) | 23.8 μg/week | 95% Confidence Interval 26.5 |
| Chronic Kidney Disease (CKD) | Darbepoetin Alfa Dose From the Switch Date Until the End of the Observation Period | Month 6 (n=769) | 25.6 μg/week | 95% Confidence Interval 25.5 |
Secondary
Dose Ratio Measured at the Time of Switch From PEG Epoetin Beta to Darbepoetin Alfa
Dose ratio is the average weekly dose of the first darbepoetin alfa dose divided by the average weekly dose of peg-epoetin beta at switch (μg darbepoetin alfa per 1 μg pegylated-epoetin beta).
Time frame: Week -1 and Week 1
Population: Primary analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Chronic Kidney Disease (CKD) | Dose Ratio Measured at the Time of Switch From PEG Epoetin Beta to Darbepoetin Alfa | 1.06 ratio |
Secondary
Hemoglobin Concentration Rate of Change by Period
The hemoglobin rate of change is the maximum monthly increase and maximum monthly decrease for the pre- and post-switch periods. Within each period, the difference was calculated between each hemoglobin value and the most recent hemoglobin value taken at least 28 days previously. The rate of change was calculated by dividing this difference by the number of days in the interval and multiplying by 28. The maximum and minimum rate of change was then determined per participant.
Time frame: Thre months prior to switch and 6 months after the switch
Population: Primary Analysis Set with available data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration Rate of Change by Period | Highest change during period | 0.64 g/dL/4 week | Standard Deviation 0.71 |
| Chronic Kidney Disease (CKD) | Hemoglobin Concentration Rate of Change by Period | Lowest change during period | -0.73 g/dL/4 week | Standard Deviation 0.86 |
| Post-switch Period | Hemoglobin Concentration Rate of Change by Period | Highest change during period | 1.17 g/dL/4 week | Standard Deviation 0.74 |
| Post-switch Period | Hemoglobin Concentration Rate of Change by Period | Lowest change during period | -1.21 g/dL/4 week | Standard Deviation 0.88 |
Secondary
PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch
Mean weekly doses were calculated per participant by first calculating a mean daily dose for the interval (by dividing each dose evenly between the days bounded by its date of administration and the day before the next dose, then taking a mean of these partial doses for the days in the interval) and multiplying by 7 to convert to a weekly dose. Weekly doses \>150 μg have been excluded as they were deemed infeasible values derived by the algorithm.
Time frame: Month -3, Month -2, Month -1
Population: Primary analysis set; participants with available data at each time point (indicated by n).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Chronic Kidney Disease (CKD) | PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch | Month -3 (n=740) | 27.7 μg/week | 95% Confidence Interval 23.7 |
| Chronic Kidney Disease (CKD) | PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch | Month -2 (n=779) | 26.5 μg/week | 95% Confidence Interval 22.1 |
| Chronic Kidney Disease (CKD) | PEG Epoetin Beta Dose From the Start of the Observation Period Until the Switch | Month -1 (n=783) | 27.4 μg/week | 95% Confidence Interval 24.2 |
Secondary
Percentage of Participants With Hemoglobin Excursions
The percentage of participants with at least one hemoglobin excursion, defined as hemoglobin concentrations below 10.0 g/dL and above 12.0 g/dL during the pre- and post-switch periods.
Time frame: Month -3, -2, -1, 1, 2, 3, 4, 5 and 6
Population: Primary analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month -1 | 15.7 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month 3 | 11.7 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month -2 | 17.7 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month 4 | 13.8 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month 1 | 17.8 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month 5 | 12.2 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month -3 | 16.8 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month 6 | 14.6 percentage of participants |
| Chronic Kidney Disease (CKD) | Percentage of Participants With Hemoglobin Excursions | Month 2 | 13.6 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month 6 | 26.5 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month -3 | 29.0 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month -2 | 29.0 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month -1 | 24.8 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month 1 | 23.1 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month 2 | 29.3 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month 3 | 33.1 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month 4 | 32.6 percentage of participants |
| Post-switch Period | Percentage of Participants With Hemoglobin Excursions | Month 5 | 27.8 percentage of participants |