Cost Comparison Study of Darbepoetin Versus Epoetin Therapy to Treat Anemia in Hemodialysis Patients

Study Overview
=================
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.

Official Title
-----------------
A Randomized, Controlled Trial of Costs Associated With Anemia Therapy in Hemodialysis Patients Treated With Intravenous Darbepoetin Alfa Versus Epoetin Alfa

Conditions
-----------------
Anemia, Chronic Kidney Disease

Intervention / Treatment
-----------------
* Drug: Epoetin Alfa
* Drug: Darbepoetin alfa


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 19 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Epoetin alfa<br>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 to guide anemia management. The subjects in this arm will remain on epoetin for the required run-in phase followed by the 12 month active phase. | Drug: Epoetin Alfa<br>* 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.<br>* Other names: Eprex;|
| Active Comparator: Darbepoetin alfa<br>Patients who are enrolled and randomized to the Darbepoetin arm will have their epoetin discontinued at the end of the week preceding entry into the study and will switch to darbepoetin on the date that they would normally be receiving their next dose of epoetin. Switching patients to darbepoetin will be done using the conversion ratio of 200 units of epoetin to 1 μg of darbepoetin as used per week, rounded up or down to the nearest available pre-filled syringe dose available from the manufacturer. After the first Hb measurement the study algorithm will be used to guide anemia management. The subjects in this arm will remain on darbepoetin for the required run-in phase followed by the 12 month active phase. | Drug: Darbepoetin alfa<br>* 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.<br>* Other names: Aranesp;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cost of Erythropoiesis Stimulating Agent | total cost over 12 months in Canadian dollars | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin | median hemoglobin (g/L) over 12 months | 12 months | 
| Ferritin | mean ferritin (ug/L) over 12 months | 12 months | 
| Transferrin Saturation (TSAT) | median TSAT (%) over 12 months | 12 months | 
| Iron Dose | median weekly iron dose (mg) over 12 months | 12 months | 
| Iron Cost | total iron cost over 12 months in Canadian dollars | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Anemia, Hemodialysis, Erythropoiesis Stimulating Agent, Cost