Please select the eligibility criteria that correspond to the clinical trial below.
Title: Reticulocyte Dynamic and Related Hemoglobin Variability in Hemodialysis Patients Treated With Darbepoetin Alfa and C.E.R.A.: a Randomized Controlled Trial
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* adult patients \>=18 years of age;
* chronic renal anemia;
* not receiving renal replacement therapy.

Exclusion Criteria:

* women who are pregnant or lactating;
* previous treatment with erythropoietin or other erythropoietic substance;
* blood transfusion within the last 3 months;
* need for dialysis expected in the next 6 months;
* administration of another investigational drug within 30 days preceding study start, or during the study.
B: Inclusion Criteria

1. Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.
2. On IV epoetin alfa or beta maintenance therapy continuously prescribed for a minimum of 8 weeks prior to randomization.
3. Four consecutive hemoglobin values with a mean ≥ 10.0 and ≤ 12.0 g/dL during the Screening Period.

Exclusion Criteria

1. Females who are pregnant or breast-feeding.
2. Known intolerance to any erythropoiesis stimulating agent or pegylated molecule or to all parenteral iron supplementation products.
3. Known bleeding or coagulation disorder.
4. Known hematologic disease or cause of anemia other than renal disease
5. Poorly controlled hypertension.
6. Evidence of active malignancy within one year prior to randomization.
7. Temporary (untunneled) dialysis access catheter.
8. A scheduled kidney transplant.
9. A scheduled surgery that may be expected to lead to significant blood loss.
C: Inclusion Criteria

1. Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.
2. On intravenous epoetin alfa maintenance therapy continuously prescribed for a minimum of 8 weeks prior to randomization.
3. Four consecutive hemoglobin values with a mean ≥ 10.0 and ≤ 12.0 g/dL during the screening period

Exclusion Criteria

1. Females who are pregnant or breast-feeding.
2. Known intolerance to any erythropoiesis stimulating agent (ESA) or pegylated molecule or to all parenteral iron supplementation products.
3. Known bleeding or coagulation disorder.
4. Known hematologic disease or cause of anemia other than renal disease
5. Poorly controlled hypertension
6. Evidence of active malignancy within one year prior to randomization.
7. Temporary (untunneled) dialysis access catheter.
8. A scheduled kidney transplant
9. A scheduled surgery that may be expected to lead to significant blood loss.
D: 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

Answer: D