Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Controlled, Open Label, Multicenter, Parallel-group Study to Compare the Effect of Mircera With That of Darbepoetin Alfa, Administered Intravenously at Extended Dosing Intervals, for the Maintenance Treatment of Anemia in Patients With Chronic Kidney Disease Who Are on Hemodialysis
Brief Summary: This 2 arm study will compare the efficacy and safety of Mircera and darbepoetin alfa, administered at extended dosing intervals, in the maintenance treatment of anemia in patients with chronic kidney disease (CKD) who are on hemodialysis. Eligible patients receiving once-weekly intravenous (IV) darbepoetin alfa maintenance treatment will be randomized to receive either intravenous Mircera once a month (at a starting dose of 120, 200 or 360 micrograms/month, depending on the weekly dose of darbepoetin alfa prior to start of study) or intravenous darbepoetin alfa every 2 weeks before switching to once monthly administration. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.


Options:
A: 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;
B: Inclusion Criteria:

* ≥ 18 years of age
* Diagnosis of chronic kidney disease with eGFR of 15-59 mL/min/1.73 m2 (MDRD equation)
* Two consecutive screening Hb values taken at least 7 days apart must each be \<10.0 g/dL
* TSAT ≥ 15%

Exclusion Criteria:

* Upper or lower GI bleeding within 6 months before enrolment
* ESA use within 12 weeks before enrolment
* Uncontrolled hypertension
* Systemic haematologic disorders
* Prior history within 12 weeks before enrollment of events including: Acute myocardial ischemia, unstable angina, myocardial infarction, hospitalization for congestive heart failure, stroke or transient ischaemic attack, limb ischaemia, deep vein thrombosis, thromboembolism.
* Grand mal seizure within 6 months prior to enrolment
* Evidence of, or received chemotherapy or radiation therapy for, a malignancy within 5 years prior to enrolment.
* Red blood cell transfusion within 12 weeks prior to enrolment
* Androgen therapy within 8 weeks prior to enrolment
* Pregnancy or breast feeding, or inadequate contraception
* Currently receiving immunosuppressive therapy
C: Inclusion Criteria:

* Chronic Kidney Disease:Glomerular filtration rate (GFR) \> 15 mL/min and \> 50 mL/min as calculated by the central lab. HB\<11 g/dL upon study enrollment. The GFR for assessment of patient eligibility will be determined using the formula derived from the Modification of Diet for Renal Disease (MDRD) Study.

Exclusion Criteria:

* Pregnant or lactating women
* Presence of uncontrolled hypertension
* Known hypersensitivity to mammalian cell-derived products or human albumin
* Active gastrointestinal bleeding
* Iron overload defined as a transferrin saturation \>70% or ferritin \>1000 ng/mL
* History of frequent blood transfusions in the past 6 months
* Unstable angina or angina pectoris at rest
* Severe chronic obstructive pulmonary disease requiring routine use of supplemental oxygen
* Severe liver dysfunction that is defined by an international normalized ratio \>2.0, not caused by an anticoagulant
* Severe malnutrition
* Active hematological disease (eg, sickle cell anemia, thalassemia)
* Active malignancy (usually defined as malignancy requiring current chemotherapy or radiotherapy)
* Patients with current seizure disorder or activity
* Patients currently receiving RRT (patient can not be on dialysis or have had a kidney transplant)
* Patients who have received Epoetin Alpha within 6 weeks prior to study entry
D: Inclusion Criteria:

* Aged between 18 and 70
* ESRD patients who are on hemodialysis for ≥3 months.
* Hb level 8- 11.5 g/dl
* Patients are on adequate hemodialysis: the minimally adequate dose of hemodialysis given 3 times per week should be a spKt/V (single-pool delivered Kt/V; clearance of urea x dialysis time/volume of distribution) of 1.2 per dialysis. For treatment periods of less than 5 hours, an alternative minimum dose is a urea reduction rate (URR) of 65%. All types of hemodialysis systems and hemodiafiltration, including high-flux membranes are allowed as long as there is no plan to change the patient's regimen during the study.
* Sufficient iron stores, defined as serum ferritin ≥ 200 ng/ml and transferrin saturation ≥20%. (Patients not meeting these criteria may receive iron supplementation therapy during the Screening and stabilization period to appropriately correct their iron store deficiency to meet the criterion required for randomization);
* Ability to comply with study medication use, study visits, and study procedures as judged by the investigator;
* Females of childbearing potential agree to use an acceptable method of birth control (e.g., abstinence, hormonal or barrier methods, partner sterilization, or IUD) for the duration of the study.
* Qualified and willing to sign the informed consent form with the commitment of complying with all the scheduled visits, and study procedures as judged by the investigator;
* In any circumstances that potential participants are not able to give consent, it may be given by responsible parents or guardian.

Exclusion Criteria:

* Uncontrolled hypertension (defined as pre-dialysis diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥180 mmHg);
* Anemia secondary to other causes different to the CKD (e.g. multiple myeloma, aplastic anemia, leukemia;....)
* Decompensated liver failure;
* Clinical evidence of concurrent uncontrolled hyperparathyroidism (defined as serum parathyroid hormone (iPTH) \> 800 pg/ml);
* Heart failure \[New York Heart Association (NYHA) class III and IV\];
* Unstable angina pectoris, active cardiac disease, stroke and/or cardiac infarction within the last 6 months;
* History of or active blood coagulation disorders including DVT, PTE, native access Thrombosis during last 6 months.
* Thrombocytosis (platelet count \> 500,000/µl);
* Thrombocytopenia (platelet count \< 100,000/µl);
* White blood cell count \< 3,000/µl);
* White blood cell count \>15,000/µl)
* Recent Bleeding (acute or chronic bleeding within three months prior to screening);
* Suspicion of or confirmed occult bleeding (increased reticulocyte count);
* Clinical evidence of concurrent systemic infection, or inflammatory disease (e.g; diabetic foot, bed sore, access infection, CRP\> 30 mg/l,...)
* Currently receiving treatment for epilepsy;
* Major surgery within 3 months prior to randomization and during the conduct of the trial (except vascular access surgery);
* Concomitant immunosuppressive therapy; patients on a short course of steroids (up to 7 days), topical or intranasal steroids are allowed in the study;
* History of any malignant disease within the last 5 years (except excised non-melanoma skin cancer);
* Women who are pregnant or breastfeeding;
* Known history of severe drug-related allergies;
* Known history of drug related allergy to Erythropoietin or one of the ingredients of the test or the reference products or hypersensitivity to mammalian-derived products;
* Transplant received within one year prior to the start of the study;
* Simultaneous participation in another clinical study or having received an Investigational Medicinal Product within three months before randomization in this study.
* Psychiatric, addictive (drugs or alcohol) or any other disorder that compromises the ability to give an informed consent;
* Any red blood cell transfusion during the last 3 months (measured at the time of eligibility verification);
* Primary hematological disorder (e.g. myelodysplastic syndrome, myeloma, sickle cell anemia, hematological malignancy, multiple myeloma hemolytic anemia);
* known resistance to the rHuEPO defined by a requirement \> 450 IU/kg/week by IV or 300 IU/kg/week by SC, equivalent to approximately 20.000 IU/week SC and in absence of iron deficiency;
* who have suffered an event of active bleeding in the 30 days prior to the beginning of the study;
* Morbid obesity, defined by a Body Mass Index (BMI) \> 37 kg/m2 in women and \> 40 kg/m2 in men.

Answer: A