A Study to Assess All-Cause Mortality and Cardiovascular Morbidity in Participants With Chronic Kidney Disease (CKD) on Dialysis and Those Not on Renal Replacement Therapy Receiving Methoxy Polyethylene Glycol-Epoetin Beta (Mircera) or Reference Erythropoietin Stimulating Agents (ESAs)
Condition: Chronic Renal Anemia
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Intervention: Darbepoetin Alfa; Epoetin Alfa; Epoetin Beta; methoxy polyethylene glycol-epoetin beta
Intervention description: Darbepoetin alfa will be administered as per approved label.; Epoetin alfa will be administered as per approved label.; Epoetin beta will be administered as per approved label.; Participants who are currently not being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta administered at a starting dose of 0.6 mcg/kg body weight once every 2 weeks. Participants who are currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta at a dose of 120, 200 or 360 mcg once monthly (based on ESA dose administered in Week -1)
Intervention MeSH terms: Epoetin Alfa; Darbepoetin alfa
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 2825.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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