Effect of a continuous erythropoietin receptor activator (C.E.R.A.) on stable haemoglobin in patients with CKD on dialysis: once monthly administration.
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.
Locatelli
Francesco
F
Divisione di Nefrologia e Dialisi, Ospedale Alessandro Manzoni, Lecco, Italy. f.locatelli@ospedale.lecco.it
Villa
Giuseppe
G
de Francisco
Angel L M
AL
Albertazzi
Alberto
A
Adrogue
Horacio J
HJ
Dougherty
Frank C
FC
Beyer
Ulrich
U
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
D006454:Hemoglobins; D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; D004921:Erythropoietin; D011092:Polyethylene Glycols