Evaluation of maintenance of stable haemoglobin levels in haemodialysis patients converting from epoetin or darbepoetin to monthly intravenous C.E.R.A.: the MIRACEL study

Abstract

Background and objectives:

C.E.R.A., a continuous erythropoietin receptor activator, offers once-monthly dosing without compromising haemoglobin control. This study was undertaken to examine whether monthly C.E.R.A. using pre-filled syringes maintains stable haemoglobin levels when administered according to local clinical judgement.

Research, design and methods:

MIRACEL was a prospective, open-label, single-arm, multicentre study performed at 90 nephrology centres in Germany. After a 2-month screening phase, haemodialysis patients receiving epoetin or darbepoetin were converted to monthly intravenous C.E.R.A., with a 5-month titration phase followed by a 2-month evaluation phase.

Clinical trial registration:

Clinicaltrials.gov: NCT00413894

Results:

Of 661 patients screened, 424 (64.1%) started C.E.R.A. therapy (previous treatment: 72.2% epoetin, 27.8% darbepoetin); 416 were eligible for inclusion in the intent-to-treat population. A mean of two C.E.R.A. dose changes were required during the 7-month treatment period. The primary efficacy variable, haemoglobin within 11–12.5 g/dL or 10–13 g/dL during the evaluation phase, was achieved in 109 (30.8%) and 265 (74.9%) of the 354 evaluable patients, respectively, with no differences observed between patients formerly receiving epoetin or darbepoetin or different dosing frequencies. During the screening, titration and evaluation phases, mean haemoglobin was 11.7 ± 0.7 g/dL, 11.6 ± 0.9 g/dL and 11.4 ± 1.0 g/dL, respectively, and 90.6% (377/416), 70.4% (293/416) and 82.9% (345/416) of patients exhibited ≤ 1 g/dL change from phase-specific individual means. C.E.R.A. was well-tolerated with a safety profile similar to that reported in phase III studies.

Conclusions:

In this single-arm, open-label, multicentre study, conversion of a large population of haemodialysis patients from epoetin or darbepoetin to monthly C.E.R.A. administration using pre-filled syringes was shown to be practical, convenient and offer good control of haemoglobin levels, regardless of the previous type of therapy or dosing frequency.

Key words::

• Continuous erythropoietin receptor activator (C.E.R.A.)
• Conversion
• Erythropoiesis stimulating agents
• Haemodialysis
• Haemoglobin levels

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Errata

Transparency

Declaration of funding

The study was sponsored by Roche Pharma AG, Germany. The sponsor reviewed the manuscript. The decision to publish was made by D.F.

Declaration of financial/other relationships

D.F. has disclosed receiving research grants from Roche, Ortho Biotech; receiving speaker’s fees from Roche, Amgen and Ortho Biotech; and membership of advisory boards for Roche and Amgen. F.D. has disclosed receiving speaker’s fees from Roche, Hexal, Amgen, Shire and Ortho Biotech. All other authors have disclosed that they have no relevant financial relationships.

Peer reviewers may receive honoraria from CMRO for their review work. Peer Reviewer 1 has disclosed that he/she has acted as a consultant/advisor to, and a member of the speakers’ bureau for Vifor. Peer Reviewer 2 has disclosed that he/she has no relevant financial relationships.

Acknowledgements

The first draft of this publication was prepared by a medical writer (Caroline Dunstall), who also coordinated revised drafts from authors to the point at which all authors approved the final version. We are especially grateful to our colleagues Drs. Bozkurt (Daun), Schettler (Bovenden), Graf (Fulda) and Bockreiss (Oberschleissheim). This editorial support was funded by Roche Pharma AG, Germany. The authors thank A. Wiggenhauser, M. Wahl and L. Gnuegge for contributing to this study.

An abstract of these data were presented at the EDTA-ERA congress in 2009.