Anemia, Chronic Kidney Disease
Conditions
Keywords
Anemia, Hemodialysis, Erythropoiesis Stimulating Agent, Cost
Brief summary
The purpose of this study is to determine if there is a cost difference between darbepoetin alfa and epoetin alfa when used intravenously to treat anemia in hemodialysis patients.
Detailed description
Eligible hemodialysis patients who are currently receiving an erythropoiesis stimulating agent (ESA) who enrol and sign consent will be randomized on a 1:1 basis to either remain on epoetin alfa or switch to darbepoetin alfa as their anemia therapy. Patients will be dosed with the assigned drug using a study algorithm to maintain their hemoglobin (Hb) level within the currently recommended range (100-120 g/L). There will be an initial run in period of a minimum of six weeks to ensure the patient's hemoglobin is stable within the target range. The trial itself will run for a subsequent twelve months (active phase). Every effort will be made to ensure that Hb stays within the target range during the study period. The primary outcome will be the total cost of each ESA therapy over the twelve month active phase. Data including Hgb, iron indices and dosing, and clinical events will be obtained from electronic sources and from the attending physicians and/or the clinical pharmacist.
Interventions
DRUGEpoetin Alfa
The investigator will adjust epoetin doses as per the study algorithm during the run-in (every two weeks) and active phases (every four weeks). This will continue until the 12 month active phase is complete or the patient is withdrawn from the study. All epoetin will be administered intravenously through a hemodialysis machine port using a manufacturer-provided pre-filled syringe. It is not anticipated that a subject will require a dose of epoetin \> 30 000 units weekly. If this occurs the dose will not be escalated any higher. Such a patient would likely meet the criteria for study withdrawal. Intravenous iron will be given as per the study algorithm and only one formulation of iron is used, sodium ferric gluconate.
DRUGDarbepoetin alfa
The investigator will adjust darbepoetin doses as per the study algorithm during the run-in (every two weeks) and active phases(every four weeks). This will continue until the 12 month active phase is complete or the patient is withdrawn from the study. All darbepoetin will be administered intravenously through a hemodialysis machine port using a manufacturer-provided pre-filled syringe. It is not anticipated that a subject will require a dose of darbepoetin \>150µg weekly. If this occurs the dose will not be escalated any higher. Such a patient would likely meet the criteria for study withdrawal. Intravenous iron will be given as per the study algorithm and only one formulation of iron is used, sodium ferric gluconate.
Sponsors
Andrea L Woodland
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* age ≥19 years * receiving in-center hemodialysis two or more times weekly * anemia requiring erythropoiesis stimulating (ESA) agent therapy OR a hemoglobin(Hb)\<100g/L in the absence of other causes of anemia * if female, must be using an approved method of contraception or judged unable to become pregnant * able to give informed consent
Exclusion criteria
* acute kidney injury likely to resolve * plans to change to peritoneal dialysis or home hemodialysis, or planned transplant from a living donor * expected lifespan of less than six months due to a medical condition other than chronic kidney disease * current hematologic condition that may cause anemia * use of medications known to cause anemia * use of any investigational drug or androgen within 90 days of screening * significant bleeding within 30 days of screening * red blood cell transfusion(s) within 30 days of screening * documented or suspected pure red cell aplasia (PRCA) * current iron deficiency * documented allergy or intolerance to intravenous sodium ferric gluconate * known or probable ESA resistance * uncontrolled hypertension * an intention to relocate to a different dialysis center in the near future
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cost of Erythropoiesis Stimulating Agent | 12 months | total cost over 12 months in Canadian dollars |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin | 12 months | median hemoglobin (g/L) over 12 months |
| Ferritin | 12 months | mean ferritin (ug/L) over 12 months |
| Transferrin Saturation (TSAT) | 12 months | median TSAT (%) over 12 months |
| Iron Dose | 12 months | median weekly iron dose (mg) over 12 months |
| Iron Cost | 12 months | total iron cost over 12 months in Canadian dollars |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Epoetin Alfa Patients who are enrolled and randomized to the Epoetin arm will remain on their current dose and frequency. After the first hemoglobin (Hb) measurement the study algorithm will be used. The subjects will remain on epoetin for the required run-in phase followed by the 12 month active phase.
The investigator will adjust epoetin doses as per the study algorithm during the run-in and active phases. This will continue until the 12 month active phase is complete or the patient is withdrawn from the study.
All epoetin will be administered intravenously through a hemodialysis machine port using a manufacturer-provided pre-filled syringe.
It is not anticipated that a subject will require a dose of epoetin \> 30 000 units weekly. If this occurs the dose will not be escalated any higher.
Intravenous iron will be given as per the study algorithm and only one formulation of iron is used, sodium ferric gluconate. | 24 |
| Darbepoetin Alfa Patients who are randomized to the Darbepoetin arm will have their epoetin and will switch to darbepoetin on the date that they would normally be receiving their next dose of epoetin.
Switching patients will be done using the conversion ratio of 200 units of epoetin to 1 μg of darbepoetin as used per week, rounded to the nearest pre-filled syringe available from the manufacturer.
After the first Hb measurement the study algorithm will be used.
The investigator will adjust darbepoetin doses as per the study algorithm during the run-in and active phases. This will continue until the 12 month active phase is complete or the patient is withdrawn from the study.
All darbepoetin will be administered intravenously through a hemodialysis machine port.
It is not anticipated that a subject will require a dose of darbepoetin \>150µg weekly. If this occurs the dose will not be escalated any higher.
Intravenous iron will be given as per the study algorithm, sodium ferric gluconate. | 26 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | changed to Peritoneal Dialysis | 0 | 1 |
| Overall Study | Death | 1 | 3 |
| Overall Study | moved away | 1 | 0 |
| Overall Study | transplant | 1 | 1 |
Baseline characteristics
| Characteristic | Epoetin Alfa | Darbepoetin Alfa | Total |
|---|---|---|---|
| Age, Continuous | 59.8 years STANDARD_DEVIATION 13.3 | 61 years STANDARD_DEVIATION 15.1 | 60.49 years STANDARD_DEVIATION 13.98 |
| Region of Enrollment Canada | 24 participants | 26 participants | 50 participants |
| Sex: Female, Male Female | 13 Participants | 6 Participants | 19 Participants |
| Sex: Female, Male Male | 11 Participants | 20 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 24 | 3 / 26 |
| other Total, other adverse events | 0 / 24 | 0 / 26 |
| serious Total, serious adverse events | 0 / 24 | 0 / 26 |
Outcome results
Primary
Cost of Erythropoiesis Stimulating Agent
total cost over 12 months in Canadian dollars
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoetin Alfa | Cost of Erythropoiesis Stimulating Agent | 4178.70 dollars Canadian |
| Darbepoetin Alfa | Cost of Erythropoiesis Stimulating Agent | 2302.92 dollars Canadian |
Secondary
Ferritin
mean ferritin (ug/L) over 12 months
Time frame: 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Epoetin Alfa | Ferritin | 847.58 ug/L | Standard Deviation 272.88 |
| Darbepoetin Alfa | Ferritin | 726.29 ug/L | Standard Deviation 377.13 |
Secondary
Hemoglobin
median hemoglobin (g/L) over 12 months
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoetin Alfa | Hemoglobin | 108 g/L |
| Darbepoetin Alfa | Hemoglobin | 109.8 g/L |
Secondary
Iron Cost
total iron cost over 12 months in Canadian dollars
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoetin Alfa | Iron Cost | 726.56 canadian dollars |
| Darbepoetin Alfa | Iron Cost | 750 canadian dollars |
Secondary
Iron Dose
median weekly iron dose (mg) over 12 months
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoetin Alfa | Iron Dose | 40.36 mg/week |
| Darbepoetin Alfa | Iron Dose | 41.67 mg/week |
Secondary
Transferrin Saturation (TSAT)
median TSAT (%) over 12 months
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Epoetin Alfa | Transferrin Saturation (TSAT) | 26.71 percentage saturation |
| Darbepoetin Alfa | Transferrin Saturation (TSAT) | 28.58 percentage saturation |