Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Randomized, Two Armed, Parallel, Double Blind (Patient and Assessor Blinded), Active Controlled Non Inferiority Clinical Trial to Determine the Non Inferior Therapeutic Efficacy and Safety Between CinnaPoietin® (Beta Erythropoietin) and Eprex® (Epoetin Alpha) on the Treatment of Anemia in ESRD Hemodialysis Patients
Brief Summary: This Phase III, randomized, two-armed, parallel, double-blind, active-controlled clinical trial is designed to compare efficacy and safety of CinnaPoietin® (Beta erythropoietin) and Eprex® (epoetin alpha) on the treatment of anemia in 156 End-Stage Renal Disease hemodialysis patients. 156 patients have been planned to randomize and assign to receive CinnaPoietin® or Eprex® for a 26-week period. Administration dose for patients who are treated with erythropoietin is the similar dose of the previously administered amount (IV or SC without any change). After then, dose adjustment will be made based on patients' response. The primary objective of this study is to compare the efficacy of CinnaPoietin® with Eprex®. The secondary objectives of this study are further comparison and evaluation of efficacy along with safety between CinnaPoietin® and Eprex®.


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:

* 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;
D: Inclusion Criteria:

* Males anf Females aged between 18 and 75
* Patients having given their written consent
* Patient determined to participate in the test and to respect the requirements
* Patient covered by a social insurance
* Patient to be kidney transplanted (from a cadaveric donor)
* Patient benefiting from the 1st or 2nd kidney transplant
* Patient formerly treated by peritoneal dialysis or hemodialysis
* Patient receiving a graft with risk of delayed graft function (score\> 7 combining age of the donor, ischemia time, receiver ethnicity and cause of death)
* Patient to receive treatment with basiliximab, mycophenolate mofetil, tacrolimus and corticosteroid

Exclusion Criteria:

* Patient Pregnant or nursing
* Patient with a disability that does not ensure the good understanding of the study and its imperatives , or patient having dependency (alcohol, drugs)
* Patient receiving doses of epoetin beta or alpha\> 30,000 IU / week or darbepoetin\> 150 microg / week before transplanting
* Patient who has participated in a clinical trial in the last month or currently included in another test
* Patient in safeguarding justice, guardianship or trusteeship
* Patient receiving a third transplant or hyper immune or who have a positive historic cross-match
* Patient receiving a preemptive transplant
* graft from a living donor
* graft with 3 or more arteries
* Multi-Organ Transplantation
* Patient with heart failure stage\> III
* Patients with unstable ischemic heart disease, or have had a major coronary event less than 6 months, stroke or TIA \<6 months or symptomatic arteritis of lower limbs stage ≥ 3
* Patients with active viral infection: hepatitis B, C (PCR + only) or HIV
* Patient with a history of anemia from erythroblastopenia
* Patient receiving anticoagulant treatment(AVK) before renal transplantation and to be continued after transplant
* Patient with a preoperative rate Hb\> 14 g / dL (before ultrafiltration)
* A patient with known hypersensitivity to the active substance or to any of the excipients, or to benzoic acid
* Patients with poorly controlled hypertension in the weeks before transplantation (Diastolic Blood Pressure ≥ 110 mm Hg with more than 3 antihypertensive drugs)

Answer: B