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)

Roche

Status and phase: Completed; Phase 4

Conditions: Chronic Renal Anemia

Treatments: Drug: Darbepoetin Alfa; Drug: methoxy polyethylene glycol-epoetin beta; Drug: Epoetin Beta; Drug: Epoetin Alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT00773513

BH21260

2007-005129-31

Details and patient eligibility

About

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.

Enrollment: 2,825 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

2,825 participants in 2 patient groups

Erythropoiesis Stimulating Agents

Active Comparator group

Description:

Participants will receive reference ESA according to approved label. The approved reference ESA compounds in the study will be darbepoetin alfa, epoetin alfa and epoetin beta.

Treatment:

Drug: Epoetin Alfa

Drug: Epoetin Beta

Drug: methoxy polyethylene glycol-epoetin beta

Drug: Darbepoetin Alfa

Methoxy Polyethylene Glycol-Epoetin Beta

Experimental group

Description:

Participants not currently being treated with an ESA will receive methoxy polyethylene glycol-epoetin beta iv or sc once every 2 weeks for correction of renal anemia (target Hb 10-12 g/dL). Once corrected and in participants currently being treated with an ESA, methoxy polyethylene glycol-epoetin beta will be administered once monthly.

Treatment:

Drug: Epoetin Alfa

Drug: methoxy polyethylene glycol-epoetin beta

Drug: Darbepoetin Alfa