Anemia
Conditions
Brief summary
This 2 arm study will compare the efficacy and safety of monthly administration of intravenous (IV) Mircera versus epoetin alfa for the maintenance of hemoglobin levels in hemodialysis patients with chronic renal anemia. Participants currently receiving maintenance treatment with epoetin alfa will be randomized either to receive monthly injections of 120, 200 or 360 micrograms Mircera, with the starting dose derived from the dose of epoetin alfa they were receiving in the week preceding study start, or to continue on epoetin alfa treatment. The anticipated duration of study is 32 weeks, and the target sample size is 146 participants.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta
120, 200 or 360 micrograms iv/month (starting dose)
DRUGEpoetin alfa
As prescribed
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* chronic renal anemia; * continuous iv maintenance epoetin alfa therapy, with the same dosing interval during the previous month to and during SVP; * regular hemodialysis for greater than or equal to (\>=) 3 months
Exclusion criteria
* transfusion of red blood cells during previous 2 months * poorly controlled hypertension requiring interruption of epoetin alfa treatment in previous 6 months;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained Average Hemoglobin (Hb) Concentration Within Plus Minus (+/-) 1 Grams Per Deciliter (g/dL) of Their Reference Hb and Between 10 and 12 g/dL During the EEP | EEP (Week 16 to 23) | Participants who maintained average Hb concentration within +/-1 g/dL of their reference Hb and between 10 to 12 g/dL during EEP are reported. The reference Hb value was defined on the basis of all assessments at Weeks -4, -3, -2, -1 and 0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hb Concentrations Between Baseline SVP and the EEP | SVP (Week -4 to -1), EEP (Week 16 to 23) | Change in Hb concentration between baseline SVP and the EEP was evaluated by subtracting the mean of Hb concentration during the SVP (Weeks -4 to -1) with the mean of Hb concentration during the EEP (Weeks 16 to 23). |
| Percentage of Participants Who Maintained Hb Concentration Between 10 and 12 g/dL Throughout the EEP | EEP (Week 16 to 23) | Participants who maintained Hb concentration between 10 to 12 g/dL throughout the EEP are reported. |
| Mean Time Spent in Hb Range 10-12 g/dL | SVP (Week -4 to -1), DTP (Week 0 to 15), and EEP (Week 16 to 23) | — |
| Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP (Week 0 to 15) and EEP (Week 16 to 23) | — |
| Percentage of Participants Who Received Red Blood Cell (RBC) Transfusions During DTP and EEP | DTP (Week 0 to 15) up to EEP (Week 16 to 23) | RBC transfusions could be given during the study in case of medical need, i.e., in severely anemic participants with recognized symptoms or signs of anemia (e.g., in participants with acute blood loss, with severe angina, or whose hemoglobin decreased to critical levels). |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| C.E.R.A Participants received starting dose of 120, 200 or 360 mcg of C.E.R.A IV once monthly for 6 months. The starting dose was based on the dose of epoetin alfa administered in Week -1. | 65 |
| Epoetin Alfa Participants received IV injection of 6000 IU of epoetin alfa q3wk during the SVP (Week -4 to -1), 7443 IU of epoetin alfa q3wk during DTP (Week 0 to 15), and 7363 IU of epoetin alfa q3wk during EEP (Week 16 to 23) up to 23 weeks. | 36 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Blood Transfusion | 7 | 1 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Dialysis Out of Centre for 3 Months | 0 | 1 |
| Overall Study | Holidays Dialysis Out | 1 | 0 |
| Overall Study | Incorrect Epoetin Beta Administration | 1 | 0 |
| Overall Study | Insufficient Therapeutic Response | 2 | 0 |
| Overall Study | Principal Investigator Decision | 0 | 1 |
| Overall Study | Renal Transplantation | 3 | 1 |
Baseline characteristics
| Characteristic | C.E.R.A | Epoetin Alfa | Total |
|---|---|---|---|
| Age, Continuous | 65.2 years STANDARD_DEVIATION 14.93 | 64.5 years STANDARD_DEVIATION 16.62 | 64.9 years STANDARD_DEVIATION 15.47 |
| Sex: Female, Male Female | 29 Participants | 17 Participants | 46 Participants |
| Sex: Female, Male Male | 36 Participants | 19 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 65 | 9 / 36 |
| serious Total, serious adverse events | 16 / 65 | 4 / 36 |
Outcome results
Primary
Percentage of Participants Who Maintained Average Hemoglobin (Hb) Concentration Within Plus Minus (+/-) 1 Grams Per Deciliter (g/dL) of Their Reference Hb and Between 10 and 12 g/dL During the EEP
Participants who maintained average Hb concentration within +/-1 g/dL of their reference Hb and between 10 to 12 g/dL during EEP are reported. The reference Hb value was defined on the basis of all assessments at Weeks -4, -3, -2, -1 and 0.
Time frame: EEP (Week 16 to 23)
Population: Per Protocol (PP) population was as a subset of the ITT population who completed the study without any major protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A | Percentage of Participants Who Maintained Average Hemoglobin (Hb) Concentration Within Plus Minus (+/-) 1 Grams Per Deciliter (g/dL) of Their Reference Hb and Between 10 and 12 g/dL During the EEP | 45.45 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Maintained Average Hemoglobin (Hb) Concentration Within Plus Minus (+/-) 1 Grams Per Deciliter (g/dL) of Their Reference Hb and Between 10 and 12 g/dL During the EEP | 55.17 percentage of participants |
p-value: 0.4778Fisher Exact
Secondary
Change in Hb Concentrations Between Baseline SVP and the EEP
Change in Hb concentration between baseline SVP and the EEP was evaluated by subtracting the mean of Hb concentration during the SVP (Weeks -4 to -1) with the mean of Hb concentration during the EEP (Weeks 16 to 23).
Time frame: SVP (Week -4 to -1), EEP (Week 16 to 23)
Population: ITT population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A | Change in Hb Concentrations Between Baseline SVP and the EEP | -0.35 g/dL | Standard Deviation 1.32 |
| Epoetin Alfa | Change in Hb Concentrations Between Baseline SVP and the EEP | 0.32 g/dL | Standard Deviation 1.06 |
Secondary
Mean Time Spent in Hb Range 10-12 g/dL
Time frame: SVP (Week -4 to -1), DTP (Week 0 to 15), and EEP (Week 16 to 23)
Population: ITT population. Here, n = participants who were evaluable for each category, for respective arm groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Time Spent in Hb Range 10-12 g/dL | SVP (Week -4 to -1) (n=65, 36) | 26.7 days | Standard Deviation 4.46 |
| C.E.R.A | Mean Time Spent in Hb Range 10-12 g/dL | DTP (Week 0 to 15) (n=65, 36) | 67.5 days | Standard Deviation 33.92 |
| C.E.R.A | Mean Time Spent in Hb Range 10-12 g/dL | EEP (Week 16 to 23) (n=55, 32) | 32.2 days | Standard Deviation 18.25 |
| Epoetin Alfa | Mean Time Spent in Hb Range 10-12 g/dL | SVP (Week -4 to -1) (n=65, 36) | 27.1 days | Standard Deviation 4.74 |
| Epoetin Alfa | Mean Time Spent in Hb Range 10-12 g/dL | DTP (Week 0 to 15) (n=65, 36) | 72.9 days | Standard Deviation 37.03 |
| Epoetin Alfa | Mean Time Spent in Hb Range 10-12 g/dL | EEP (Week 16 to 23) (n=55, 32) | 28.9 days | Standard Deviation 21.53 |
Secondary
Percentage of Participants Who Maintained Hb Concentration Between 10 and 12 g/dL Throughout the EEP
Participants who maintained Hb concentration between 10 to 12 g/dL throughout the EEP are reported.
Time frame: EEP (Week 16 to 23)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A | Percentage of Participants Who Maintained Hb Concentration Between 10 and 12 g/dL Throughout the EEP | 32.7 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Maintained Hb Concentration Between 10 and 12 g/dL Throughout the EEP | 40.6 percentage of participants |
Secondary
Percentage of Participants Who Received Red Blood Cell (RBC) Transfusions During DTP and EEP
RBC transfusions could be given during the study in case of medical need, i.e., in severely anemic participants with recognized symptoms or signs of anemia (e.g., in participants with acute blood loss, with severe angina, or whose hemoglobin decreased to critical levels).
Time frame: DTP (Week 0 to 15) up to EEP (Week 16 to 23)
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A | Percentage of Participants Who Received Red Blood Cell (RBC) Transfusions During DTP and EEP | 12.3 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Received Red Blood Cell (RBC) Transfusions During DTP and EEP | 2.8 percentage of participants |
Secondary
Percentage of Participants Who Required Dose Adjustments During the DTP and EEP
Time frame: DTP (Week 0 to 15) and EEP (Week 16 to 23)
Population: Safety population included all those participants who were treated with at least one dose of the trial medication and had a safety follow-up, whether withdrawn prematurely or not. Here, n = participants who were evaluable for each category, for respective arm groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: No dose change (n=65, 36) | 30.8 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Any dose change (n=65, 36) | 67.7 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Dose increased (n=65, 36) | 18.5 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Dose decreased (n=65, 36) | 24.6 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Dose decreased and increased (n=65, 36) | 24.6 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP:Only one dose changed (n=65,36) | 1.5 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: No dose change (n=55, 32) | 60.0 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Any dose change (n=55, 32) | 30.9 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Dose increased (n=55, 32) | 20.0 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Dose decreased (n=55, 32) | 10.9 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Dose decreased and increased (n=55, 32) | 0.0 percentage of participants |
| C.E.R.A | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Only one dose changed (n=55, 32) | 9.1 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Dose decreased and increased (n=55, 32) | 3.1 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: No dose change (n=65, 36) | 44.4 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: No dose change (n=55, 32) | 65.6 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Any dose change (n=65, 36) | 55.6 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Dose decreased (n=55, 32) | 18.8 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Dose increased (n=65, 36) | 19.4 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Any dose change (n=55, 32) | 34.4 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Dose decreased (n=65, 36) | 25.0 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Only one dose changed (n=55, 32) | 0.0 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP: Dose decreased and increased (n=65, 36) | 11.1 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | EEP: Dose increased (n=55, 32) | 12.5 percentage of participants |
| Epoetin Alfa | Percentage of Participants Who Required Dose Adjustments During the DTP and EEP | DTP:Only one dose changed (n=65,36) | 0.0 percentage of participants |