Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effects of the Dose of Erythropoiesis Stimulating Agents on Cardiac-cerebrovascular Outcomes Quality of Life and Costs in Hemodialysis Patients. The Clinical Evaluation of the DOSe of Erythropoietins (C.E. DOSE) Trial
Brief Summary: Anaemia is a risk factor for death, cardiac-cerebrovascular events and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESAs) are the most used treatment option.

The purpose of this study is

1. the evaluation of biochemical markers to determine the efficacy of individual prediction of ESAs therapy
2. to determine the benefits and harms of different ESA doses therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD).


Options:
A: Inclusion Criteria:

* adult patients \>=18 years of age;
* chronic renal anemia;
* on dialysis (hemodialysis or peritoneal dialysis) therapy for at least 3 months;
* receiving sc epoetin alfa or beta for at least 3 months prior to the run-in period.

Exclusion Criteria:

* women who are pregnant, breastfeeding or using unreliable birth control methods;
* use of any investigational drug within 30 days preceding the run-in phase, or during the run-in or study treatment period.
B: 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.
C: 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
D: 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

Answer: D