ESAs, Reticulocyte Dynamic and Hemoglobin Variability

Study Overview
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Brief Summary
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Background: In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics under different ESAs and administration intervals in a collective of chronic hemodialysis patients. Methods: The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in September 2009 and lasting 2 years. Four treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference.

Official Title
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Reticulocyte Dynamic and Related Hemoglobin Variability in Hemodialysis Patients Treated With Darbepoetin Alfa and C.E.R.A.: a Randomized Controlled Trial

Conditions
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Erythropoiesis Stimulating Agent Pharmacodynamics

Intervention / Treatment
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* Drug: comparison between darbepoetin alfa and C.E.R.A. and different administration intervals


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: chronic patients aged 18 years or older, undergoing dialysis 3 times a week for at least 8 weeks before screening, necessitating continuous subcutaneous treatment with weekly Darbepoetin alfa or Erythropoietin beta to maintain hemoglobin (Hb) targets Exclusion Criteria: pregnancy; not respecting the inclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: C.E.R.A.<br>C.E.R.A. every 4 and then every 2 weeks | Drug: comparison between darbepoetin alfa and C.E.R.A. and different administration intervals<br> <br> |
| Active Comparator: Darbepoetin<br>Darbepoetin alfa every 4 and then every 2 weeks | Drug: comparison between darbepoetin alfa and C.E.R.A. and different administration intervals<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hemoglobin variability |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| differences in reticulocyte count over time |  | 2 years | 
| risk of hemoglobin overshooting (HR) |  | 2 years | 
| superiority of every 2 week administration |  | 2 years | 
| reticulocyte variability |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erythropoietin stimulating agents, Hemoglobin, Reticulocytes, Variability