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Vol. 28, No. 2, 2008
Issue release date: January 2008

C.E.R.A. Maintains Stable Control of Hemoglobin in Patients with Chronic Kidney Disease on Dialysis when Administered Once Every Two Weeks

Spinowitz B. · Coyne D.W. · Lok C.E. · Fraticelli M. · Azer M. · Dalal S. · Villa G. · Rosansky S. · Adamis H. · Beyer U.
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Background/Aims: This Phase III study examined the efficacy and safety of C.E.R.A., a continuous erythropoietin receptor activator, given once every 2 weeks (Q2W) via subcutaneous or intravenous injection using pre-filled syringes, for maintaining hemoglobin (Hb) levels in patients with chronic kidney disease (CKD) on dialysis who converted directly from epoetin therapy. Methods: Patients (n = 336) were randomized 1:1 to continue epoetin at their current dose, route and administration interval (once to three times weekly (QW–TIW)), or receive C.E.R.A. Q2W by the same route as previous epoetin treatment for 36 weeks. Dosage was adjusted to maintain patients’ Hb within ±1.0 g/dl of baseline value and within 10.0–13.5 g/dl. Primary endpoint was mean change in Hb between baseline and the evaluation period (weeks 29–36). Results: Mean change in Hb for C.E.R.A. and epoetin was 0.088 and –0.030 g/dl, respectively (endpoint Hb 11.93 and 11.86 g/dl, respectively). Analysis showed that C.E.R.A. was as effective as epoetin in maintaining Hb (p < 0.0001), and was well tolerated. The administration route had no impact on primary endpoint. Conclusion: Q2W C.E.R.A. administered using pre-filled syringes effectively maintains stable control of Hb in patients on dialysis who convert directly from epoetin QW–TIW.

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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  1. Valderrábano F, Hörl WH, Macdougall IC, Rossert J, Rutkowski B, Wauters JP: Predialysis survey on anemia management. Nephrol Dial Transplant 2003;18:89–100.
  2. Madore F, Lowrie EG, Brugnara C, Lew NL, Lazarus JM, Bridges K, Owen WF: Anemia in hemodialysis patients: variables affecting this outcome predictor. J Am Soc Nephrol 1997;8:1921–1929.
  3. Ma JZ, Ebben J, Xia H, Collins AJ: Hematocrit level and associated mortality in hemodialysis patients. J Am Soc Nephrol 1999;10:610–619.
  4. Foley RN, Parfrey PS, Morgan J, Barré PE, Campbell P, Cartier P, Coyle D, Fine A, Handa P, Kingma I, Lau CY, Levin A, Mendelssohn D, Muirhead N, Murphy B, Plante RK, Psen G, Wells GA: Effect of hemoglobin in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int 2000;58:1325–1335.
  5. Li S, Foley RN, Collins AJ: Anemia, hospitalization, and mortality in patients receiving peritoneal dialysis in the United States. Kidney Int 2004;65:1864–1869.
  6. Perlman RL, Finkelstein FO, Liu L, Roys E, Kiser M, Eisele G, Burrows-Hudson S, Messana JM, Levin N, Rajagopalan S, Port FK, Wolfe RA, Saran R: Quality of life in chronic kidney disease (CKD): a cross-sectional analysis in the Renal Research Institute-CKD study. Am J Kidney Dis 2005;45:658–666.
  7. Xue JL, Ma JZ, Louis TA, Collins AJ: Forecast of the number of patients with end-stage renal disease in the United States to the year 2010. J Am Soc Nephrol 2001;12:2753–2758.
  8. Roderick P, Davies R, Jones C, Feest T, Smith S, Farrington K: Simulation model of renal replacement therapy: predicting future demand in England. Nephrol Dial Transplant 2004;19:692–701.
  9. Ross SD, Fahrbach K, Frame D, Scheye R, Connelly JE, Glaspy J: The effect of anemia treatment on selected health-related quality-of-life domains: a systematic review. Clin Ther 2003;25:1786–1805.
  10. Regidor DL, Kopple JD, Kovesdy CP, Kilpatrick RD, McAllister CJ, Aronovitz J, Greenland S, Kalantar-Zadeh K: Associations between changes in hemoglobin and administered erythropoiesis-stimulating agent and survival in hemodialysis patients. J Am Soc Nephrol 2006;17:1181–1191.
  11. Dean BB, Dylan M, Gano A Jr, Knight K, Ofman JJ, Levine BS: Erythropoiesis-stimulating protein therapy and the decline of renal function: a retrospective analysis of patients with chronic kidney disease. Curr Med Res Opin 2005;21:981–987.
  12. KDOQI; National Kidney Foundation: Clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis 2006;47 (suppl 3):S11–S145.
  13. Locatelli F, Aljama P, Bárány P, Canaud B, Carrera F, Eckardt KU, Hörl WH, Macdougall IC, Macleod A, Wiecek A, Cameron S; European Best Practice Guidelines Working Group: Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004;19(suppl 2):ii1–ii47.

    External Resources

  14. De Cock E, Van Bellinghen L, Standaert B: Assessing provider time for anaemia management of dialysis patients using time and motion methods: a multi-centre observational study in Europe. Value Health 2002;5:581.

    External Resources

  15. Carrera F, Van Kriekinge G: Estimation of time saved when switching from recombinant human erythropoietin to darbepoetin alfa for the correction of anemia in dialysis patients. J Am Soc Nephrol 2001;16:789A.
  16. Wikström B, Gutierrez A, Jacobson S, Prütz K-G, Weiss L: Time gain with every other week administration of erythropoiesis-stimulating agents to patients in hemodialysis. Nephrol Dial Transplant 2006;21(suppl 4):iv166.
  17. Mahon A, Docherty B: Renal anaemia – the patient experience. EDTA/ERCA J 2004;30:34–37.
  18. Dougherty FC, Reigner B, Jordan P, Pannier A: C.E.R.A. (continuous erythropoiesis receptor activator): dose-response, pharmacokinetics and tolerability in Phase I multiple ascending dose studies (abstract). Proc Am Soc Clin Oncol 2004;23:603.
  19. Macdougall IC: C.E.R.A. (continuous erythropoietin receptor activator): a new erythropoiesis-stimulating agent for the treatment of anemia. Curr Hematol Rep 2005;4:436–440.
  20. Macdougall IC, Robson R, Opatrna S, Liogier X, Pannier A, Jordan P, Dougherty FC, Reigner B: Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease. Clin J Am Soc Nephrol 2006;1:1211–1215.
  21. Macdougall IC, Eckardt KU: Novel strategies for stimulating erythropoiesis and potential new treatments for anaemia. Lancet 2006;368:947–953.
  22. Besarab A, Salifu MO, Lunde NM, Bansal V, Fishbane S, Dougherty FC, Beyer U; for the BA16285 Study Investigators: Efficacy and tolerability of intravenous continuous erythropoietin receptor activator: a 19-week, phase II, multicenter, randomized, open-label, dose-finding study with a 12-month extension phase in patients with chronic renal disease. Clin Ther 2007;29:626–639.
  23. Locatelli F, Villa G, Arias M, Marchesi D, Dougherty FC, Beyer U; on behalf of the BA16286 Study Group: C.E.R.A. (continuous erythropoietin receptor activator) maintains haemoglobin levels in dialysis patients when administered subcutaneously up to once every 4 weeks (abstract). J Am Soc Nephrol 2004;15:543A.

    External Resources

  24. Besarab A, Beyer U, Dougherty FC; on behalf of the BA16285 Extension Study Group: Long-term intravenous C.E.R.A. (continuous erythropoietin receptor activator) maintains haemoglobin concentration in hemodialysis patients (abstract). Nephrology 2005;10(suppl):A312.
  25. Locatelli F, Villa G, de Francisco ALM, Albertazzi A, Adrogue HJ, Dougherty FC, Beyer U; on behalf of the BA16286 Study Investigators: Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis. Curr Med Res Opin 2007;23:969–979.
  26. Provenzano R, Besarab A, Macdougall IC, Ellison DH, Maxwell AP, Sulowicz W, Klinger M, Rutkowski B, Correa-Rotter R, Dougherty FC; on behalf of the BA16528 Study Investigators: The continuous erythropoietin receptor activator (C.E.R.A.) corrects anemia at extended administration intervals in patients with chronic kidney disease not on dialysis: results of a phase II study. Clin Nephrol 2007;67:306–317.
  27. NKF-K/DOQI: Clinical practice guidelines for anemia of chronic kidney disease; update 2000. Am J Kidney Dis 2001;27(suppl 1):S182–S238.
  28. Provenzano R, Bhaduri S, Singh AK; for the PROMPT Study Group: Extended epoetin alfa dosing as maintenance treatment for the anemia of chronic kidney disease: the PROMPT study. Clin Nephrol 2005;2:113–123.

    External Resources

  29. Canaud B, Braun J, Locatelli F,Villa G, Van Vlem B, Sanz Guajardo D, Dougherty FC: Intravenous (IV) C.E.R.A. (continuous erythropoietin receptor activator) administered once every 2 weeks maintains stable haemoglobin (Hb) levels in patients with chronic kidney disease (CKD) on dialysis (abstract). Nephrol Dial Transplant 2006;21(suppl 4):iv157.
  30. Sulowicz W, Locatelli F, Ryckelynck JP, Balla J, Csiky B, Harris K, Ehrhard P, Beyer U; on behalf of the PROTOS Study Investigators: Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis converted directly from epoetin one to three times weekly. Clin J Am Soc Nephrol 2007;2:637–646.
  31. Levin NW, Fishbane S, Valdés Cañedo F, Zeig S, Nassar GM, Moran JE, Villa G, Beyer U, Oguey D; on behalf of the MAXIMA study investigators: Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007;370:1415–1421.
  32. Klinger M, Arias M, Vargemezis V, Besarab A, Sulowicz W, Gerntholtz T, Ciechanowski K, Dougherty FC: C.E.R.A. (continuous erythropoietin receptor activator) administered at extended intervals corrects Hb levels in patients with CKD on dialysis (abstract). J Am Soc Nephrol 2006;17:620A.
  33. Macdougall IC, Walker R, Provenzano R, de Alvaro F, Locay HR, Nader PC, Locatelli F, Dougherty FC: C.E.R.A. (continuous erythropoietin receptor activator) administered at extended intervals corrects anemia and maintains stable Hb levels in patients with CKD not on dialysis (abstract). J Am Soc Nephrol 2006;17:619A.
  34. Osinski M, Wish J: Physician workforce: coming up short. Nephrol News Issues 2005;19:58–67.

    External Resources

  35. Locatelli F, Canaud B, Giacardy F, Martin-Malo A, Baker N, Wilson J: Treatment of anaemia in dialysis patients with unit dosing of darbepoetin alfa at a reduced dose frequency relative to recombinant human erythropoietin (rHuEpo). Nephrol Dial Transplant 2003;18:362–369.
  36. Reed N, Morere JF: Optimising anaemia management with epoetin beta. Oncology 2004;67(suppl 1):12–16.
  37. Scheifele DW, Skowronski D, King A, La Jeunesse CA, Bjornson GL, Parkyn H, Walker N, Stefura E: Evaluation of ready-to-use and multi-dose influenza vaccine formats in large clinic settings. Can J Public Health 2000;91:329–332.
  38. Plevin S, Sadur C: Use of a prefilled insulin syringe (Novolin Prefilled) by patients with diabetes. Clin Ther 1993;15:423–431.
  39. Maher KT, Drake WM, Besser GM, Grossman AB, Chew SL, Jenkins PJ, Kalingag LA, Fode FK, O’Sullivan-Hawketts MT, Walker DM, Monson JP: Improvements for patients and nurses using 2.5 ml prefilled syringes as the vehicle solution for suspension of Sandostatin LAR® microspheres. Endocr Abstr 2006;11:P179.
  40. Drain PK, Nelson CM, Lloyd JS: Single-dose versus multi-dose vaccine vials for immunization programmes in developing countries. Bull World Health Organ 2003;81:726–731.

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