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:

* 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
B: Inclusion Criteria:

* adult patients, \>=18 years of age;
* chronic renal anemia;
* hemodialysis 3 times weekly for \>=12 weeks before screening, and during screening/baseline period;
* receiving darbepoetin alfa maintenance therapy for \>=8 weeks before screening, and during screening/baseline period.

Exclusion Criteria:

* overt gastrointestinal bleeding within 8 weeks before screening or during screening/baseline period;
* transfusion of red blood cells within 8 weeks before screening or during screening/baseline period;
* active malignancy;
C: Inclusion Criteria:

* Age \> = 18,
* End stage kidney disease and anemia
* Treatment with hemodialysis for renal replacement therapy
* no contraindications to erythropoietin stimulating agents (ESAs) or already treated with ESAs

Exclusion Criteria:

* Patients with Hb levels \> 10 g/dl without ESAs
D: Inclusion Criteria

Subjects eligible to be entered into the study will meet all of the following criteria:

1. Adult female or male subjects; age ≥ 18 years.
2. End stage renal disease subjects treated in-center with the modality of hemodialysis for ≥ 120 days.
3. Diagnosed with anemia.
4. Administered routine Epogen therapy for at least 16 weeks by an IV route for treatment of anemia using an Epogen version of an FMCNA dosing algorithm for ESA, and did not miss more than 3 prescribed doses of Epogen within 12 weeks prior to randomization.
5. Currently using the IV Epogen version of the ESA dosing algorithm cMAB 5 (inclusive of versions 5.0, 5.1, ...) for anemia management.
6. Receiving hemodialysis at a clinic using the FMCNA dosing algorithm for IV iron that is the FMCNA standard of care treatment for iron replacement.

Exclusion Criteria

Subjects that meet any of the following criteria will be ineligible to be entered into the interventional cohort:

1. Subjects unable to provide a signed and dated informed consent for this clinical research study.
2. As determined by the Investigator, female subjects of child bearing potential who do not agree to use a highly effective method of contraception.
3. Any condition as determined by the investigator that would place a subject at an increased risk, or preclude subject's full compliance with the study procedures and visits.
4. Female subjects who are known to be or found to be, pregnant or lactating.
5. Subjects that are not a candidate for ESA therapies per the label warnings listed in the package insert for Epogen and/or contraindications to Epoetin Hospira listed in the Investigators' Brochure; or have had a known positive test for anti-rhEPO antibodies.
6. Treatment with any investigational drug within 30 days prior to randomization and throughout this clinical trial.
7. Diagnosed with any concurrent condition that could lead to greater-than-normal loss of blood, including but not limited to:

   * Menorrhagia, peptic ulcer disease, gastrointestinal bleeding, blood dyscrasia, hemoglobinopathy
   * Use of anticoagulation therapy, including warfarin with a target international normalized ratio (INR) of 2 or greater Anti-platelet therapy (e.g. aspirin or clopidogrel) is permitted, as is heparin given during hemodialysis. Low-dose warfarin is permitted and defined as the presence of at least two INR values less than or equal to 1.5 during the 120 days prior to enrollment and no values exceeding 1.5 at any time after 120 days prior to enrollment.

   Subjects started on warfarin with a known INR goal of 2.0 or greater are to receive no further treatment with the study drugs, but follow up visits can continue.

   Subjects on warfarin who meet criteria to enter the study are terminated if an INR \> 2.0 is discovered or if no INR is available for 60 days.
8. History of transfusion of any blood product in the past 3 months, or 2 or more transfusions in the past 1 year; or donated or lost \> 475 mL blood volume (including plasmapheresis) in the past 3 months.
9. Subjects currently receiving a long acting ESA, or who have received a long acting ESA in the 16 weeks prior to study randomization

Answer: A