Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Controlled, Open-Label, Multi-Centre, Parallel-Group Study To Assess All-Cause Mortality And Cardiovascular Morbidity In Patients With Chronic Kidney Disease On Dialysis And Those Not On Renal Replacement Therapy Under Treatment With MIRCERA® Or Reference ESAs.
Brief Summary: This 2 arm safety study will compare the outcome with respect to a composite endpoint of all-cause mortality and non-fatal cardiovascular events (myocardial infarction, stroke) in CKD participants either on dialysis or not receiving renal replacement therapy under treatment with methoxy polyethylene glycol-epoetin beta or reference ESAs. Participants will be randomized to receive intravenous (iv) or subcutaneous (sc) methoxy polyethylene glycol-epoetin beta at the following doses: for participants not already receiving ESA treatment, methoxy polyethylene glycol-epoetin beta will be administered at a starting dose of 0.6 micrograms per kilograms every 2 weeks (mcg/kg/2wks) iv or sc; for participants receiving maintenance ESA treatment, iv or sc methoxy polyethylene glycol-epoetin beta will be administered at an initial monthly dose of 120, 200 or 360 micrograms (mcg) depending on the weekly dose of ESA received prior to first methoxy polyethylene glycol-epoetin beta administration. Participants randomized to reference ESA treatment will receive iv or sc ESAs in accordance with their prescribed dosing information.


Options:
A: Inclusion Criteria:

* Male or female participants with symptomatic anemia associated with CKD
* Participants with renal anemia who are not treated with an ESA:
* Anemia was defined as hemoglobin (Hb) concentration less than (\<) 11.0 grams per deciliter (g/dL) (mean of 2 screening values with at least one day and a maximum of 2 weeks between measurements) with clinical indication for ESA treatment
* Participants with renal anemia who are on maintenance ESA therapy:
* If on dialysis: regular long-term hemodialysis or peritoneal dialysis therapy with the same mode of dialysis for at least 3 months before screening
* Hb concentration between 10 and 12 g/dL (mean of 2 screening values with at least one day and a maximum of 2 weeks between measurements)
* Participants with adequate iron status defined as: serum ferritin above or equal to 100 micrograms per liter or transferrin saturation above or equal to 20 percent

Exclusion Criteria:

* Contraindications to ESA treatment: uncontrolled hypertension, hypersensitivity to the active substance or any of the excipients, any other contraindication to ESA therapy
* Conditions known to cause inadequate response to ESA treatment or anemia other than symptomatic anemia associated with CKD:
* History of hemoglobinopathy
* Anemia due to hemolysis
* Pure red cell aplasia
* High likelihood of early withdrawal (for example, within 1 year) or interruption of the study
* Pregnancy or breast-feeding
* Women of childbearing potential without effective contraception
* Administration of another investigational drug within 1 month before screening or planned during the study period
B: Inclusion Criteria:

* We included adult patients with chronic renal failure on hemodialysis for more than three months at the Dialysis Unit of the Department of Nephrology, HCPA and the Center for Dialysis and Transplant (CDT), characterized as as patients on chronic regular dialysis procedure. Patients already in use of EPO for at least three months, only those taking the drug by subcutaneous and agreed to participate in the study.

Patients using different doses of EPO were included, but these were distributed across the treatment groups by randomization stratum dose of EPO, to ensure even distribution of patients in both groups.

It was considered that patients with HIV or AIDS who were in treatment for the disease with proper clinical management would be eligible for the study (as exemplified by patients with HIV or AIDS approved for inclusion on the waiting list for cadaveric kidney transplantation) .

Patients with a history of cancer or already treated in the oncological standpoint, and no signs of disease activity could be included.

Exclusion Criteria:

* Patients who had other causes of anemia defined for maintenance, for example, patients with liver cirrhosis, with a history of gastrointestinal bleeding, patients with chronic Gastro Intestinal, Genital or Urinary bleeding or other sites were excluded. Similarly patients with AIDS without treatment, hemolytic anemia, pancytopenia, thalassemia, sickle cell anemia, myelodysplasia, multiple myeloma or other cancers or inflammatory arthritis. There was also no inclusion of patients with intolerance or allergy to iron parenterally, patients without adherence to dialysis or with chronic inadequate dialysis blood flow of vascular access persistently below 250 mL / min, kt / v, as a measure of efficiency of hemodialysis, persistently \<1.2) or frequent hospitalizations considered as possible causes of inadequate response to erythropoietin.

We excluded patients with mental illness or condition that prevents the free consent and signature of informed consent, as well as previous reports of serious adverse effects to the drugs studied.

Criteria for withdrawal from the clinical trial: a view of the high morbidity of hemodialysis patients, expressed by frequent hospital clinics, it was found that patients in the study would not be withdrawn from the study due to hospitalization, provided that: the hospital did not involve surgery (except vascular access surgery or hospitalization in the intensive care unit or equivalent, or that represent otherwise, a loss of patient follow-up or co-interventions in the treatment of anemia of these).

Were withdrawn from the study patients who required blood transfusion because they have severe anemia or intervention unrelated to the usual treatment of anemia in hemodialysis patients.
C: Inclusion Criteria:

* adult patients \>=18 years of age;
* chronic renal anemia;
* on dialysis therapy for at least 12 weeks before screening;
* receiving darbepoetin alfa iv for at least 8 weeks before screening.

Exclusion Criteria:

* women who are pregnant, breastfeeding or using unreliable birth control methods;
* administration of another investigational drug within 4 weeks before screening, or during the study period.
D: Inclusion Criteria:

* Patients with end stage renal disease (stage CKD 5d), receiving stable subcutaneous maintenance therapy with Epogen® or Procrit® at least once per week
* Mean hemoglobin level between 9.0 - 11.5 g/dL during the screening period
* Adequate iron substitution

Exclusion Criteria:

* Contraindications for Erythropoiesis Stimulating Agent (ESA) therapy
* History of Pure Red Cell Aplasia (PRCA), or anti-erythropoietin (EPO) antibodies
* Known Human Immunodeficiency Virus (HIV) or Hepatitis B infection
* Hepatitis C infection on an active treatment
* Symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III and IV)
* Unstable angina pectoris, or cardiac infarction during the last 6 months prior to randomization
* Percutaneous coronary intervention, or coronary artery bypass grafting during the last 6 months prior to randomization
* History of malignancy of any organ system
* Systemic lupus erythematous
* Immunocompromized patients

Other In-/Exclusion criteria may apply

Answer: A