title: Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration.
abstract: OBJECTIVE
  This Phase II study aimed to determine the optimal dose and administration schedule of continuous erythropoietin receptor activator (C.E.R.A.) given subcutaneously (s.c.) in patients receiving dialysis converting directly from s.c. epoetin therapy 1-3 times/week. An extension phase examined long-term safety and efficacy.
  
  
  METHODS
  Patients were assigned to one of three C.E.R.A. dose groups determined by multiplying the previous weekly dose of epoetin by one of three ratios (0.4/150, 0.8/150, 1.2/150 for groups A, B and C, respectively). Within each group, patients were randomized to once weekly (QW), once every 3 weeks (Q3W) and once monthly (Q4W) schedules. Dose adjustments were not permitted for the first 6 weeks. The core study period was 19 weeks (21 weeks in the Q4W cohorts). Patients could enter a 12-month extension period at the same schedule, aiming to maintain haemoglobin (Hb) at 11-12 g/dL.
  
  
  RESULTS
  137 patients entered the core period, and 62 continued into the extension period. A dose-dependent relationship was seen in the primary efficacy variable, change in Hb standardized to a 6 week period (p < 0.0001), but effect was independent of schedule. Hb levels were maintained throughout the study, with few dose changes. C.E.R.A. was generally well tolerated and the most frequent adverse event was hypotension.
  
  
  CONCLUSIONS
  The results suggest that s.c. C.E.R.A. at up to once monthly intervals provides stable maintenance of Hb levels in dialysis patients converting directly from epoetin 1-3 times/week. Achieving tight Hb control with few dose adjustments at extended administration intervals may offer health benefits and improvements in resource management.
authors.affiliation: Divisione di Nefrologia e Dialisi, Ospedale Alessandro Manzoni, Lecco, Italy. f.locatelli@ospedale.lecco.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Villa
authors.forename: Angel L M
authors.initials: AL
authors.lastname: de Francisco
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertazzi
authors.forename: Horacio J
authors.initials: HJ
authors.lastname: Adrogue
authors.forename: Frank C
authors.initials: FC
authors.lastname: Dougherty
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beyer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000740:Anemia / Q000188:drug therapy* / Q000209:etiology*; D002908:Chronic Disease; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000150:complications* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology*; D011994:Recombinant Proteins; D006435:Renal Dialysis; D016896:Treatment Outcome
chemical_list: D006454:Hemoglobins; D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols