Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study

Abstract

Background: Extending the administration interval of erythropoiesis-stimulating agents (ESAs) represents an opportunity to improve the efficiency of anaemia management in patients with chronic kidney disease (CKD). However, effective haemoglobin (Hb) maintenance can be challenging with epoetin alfa and epoetin beta administered at extended intervals. C.E.R.A., a continuous erythropoietin receptor activator, has a unique pharmacologic profile and long half-life ( approximately 130 h), allowing administration at extended intervals. Phase III results have demonstrated that C.E.R.A. administered once every 4 weeks effectively maintains stable Hb levels in patients with CKD on dialysis.

Methods: STRIATA (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. Treatment for Anaemia) was a multicentre, open-label randomized phase III study to evaluate the efficacy and safety of intravenous C.E.R.A. administered once every 2 weeks (Q2W) for Hb maintenance following direct conversion from darbepoetin alfa (DA). Adult patients on dialysis receiving stable intravenous DA once weekly (QW) or Q2W were randomized (1:1) to continue their current DA regimen (n = 156) or receive intravenous C.E.R.A. Q2W (n = 157) for 52 weeks. Doses were adjusted to maintain Hb levels within +/- 1.0 g/dl of baseline and between 10.0 and 13.5 g/dl. The primary endpoint was the mean Hb change between baseline and the evaluation period (weeks 29-36).

Results: Most patients (>80%) received DA QW before randomization. The mean (95% CI) difference between C.E.R.A. and DA in the primary endpoint was 0.18 g/dl (-0.05, 0.41), within a pre-defined non-inferiority limit. C.E.R.A. was clinically non-inferior to DA (P < 0.0001) in maintaining Hb levels. Both treatments were well tolerated.

Conclusions: Stable Hb levels were successfully maintained in patients on haemodialysis directly converted to Q2W intravenous C.E.R.A. from DA.

Trial registration: ClinicalTrials.gov NCT00077766.

Figures

Fig. 1

Study design. DA, darbepoetin alfa; R, randomization; QW, once weekly; Q2W, once every 2 weeks.

Fig. 2

Patient populations and disposition. †Non-safety reasons were kidney transplantation (C.E.R.A., n = 14; DA, n = 6), refusal of treatment (C.E.R.A., n = 4; DA, n = 3) and failure to return (C.E.R.A., n = 2). The remaining 11 patients (C.E.R.A., n = 6; DA, n = 5) withdrew for reasons that included patient vacation, patient decision, patient instability (poor medical condition), protocol violation, discontinuation of dialysis, enrolled in nocturnal haemodialysis study and starting home dialysis. DA, darbepoetin alfa; QW, once weekly; Q2W, once every 2 weeks; ITT, intent-to-treat; PP, perprotocol; AE, adverse event.

Fig. 3

Mean monthly Hb values (intent-to-treat population). Darbepoetin alfa, DA; QW, once weekly; Q2W, once every 2 weeks; Hb, haemoglobin; SD, standard deviation; BL, baseline.

Fig. 4

Non-inferiority test for treatment differences. CI, confidence interval; ITT, intent-to-treat; PP, per-protocol; Hb, haemoglobin. P < 0.0001 for both comparisons.

Fig. 5

Individual stability of Hb mean levels (intent-to-treat population). No formal test was conducted to assess the statistical significance of between-group differences; however, the overlapping SD bars suggest any difference would not be significant. DA, darbepoetin alfa; QW, once weekly; Q2W, once every 2 weeks; Hb, haemoglobin; SD, standard deviation.