Dataset Information

A Randomized Trial of Roxadustat in Anemia of Kidney Failure: SIERRAS Study.

ABSTRACT:

Introduction

Erythropoiesis-stimulating agents, standard of care for anemia of end-stage kidney disease, are associated with cardiovascular events. We evaluated the efficacy and safety of roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis.

Methods

SIERRAS was a phase 3, randomized, open-label, active-controlled study enrolled adults on dialysis for end-stage kidney disease receiving erythropoiesis-stimulating agents for anemia. Patients were randomized (1:1) to thrice-weekly roxadustat or epoetin alfa. Doses were based on previous epoetin alfa dose and adjusted in the roxadustat arm to maintain hemoglobin at ∼11 g/dl during treatment. Epoetin alfa dosing was adjusted per US package insert. Primary efficacy endpoint was mean hemoglobin (g/dl) change from baseline averaged over weeks 28 to 52. Treatment-emergent adverse events were monitored.

Results

Enrolled patients (roxadustat, n = 370 and epoetin alfa, n = 371) had similar mean (SD) baseline hemoglobin levels (10.30 [0.66] g/dl). Mean (SD) hemoglobin changes for weeks 28 to 52 were 0.39 (0.93) and -0.09 (0.84) in roxadustat and epoetin alfa, respectively. Roxadustat was noninferior (least squares mean difference: 0.48 [95% confidence interval: 0.37, 0.59]; P < 0.001) to epoetin alfa. Tolerability was comparable between treatments.

Conclusion

In end-stage kidney disease, roxadustat was noninferior to epoetin alfa in up to 52 weeks of treatment in this erythropoietin-stimulating agent conversion study. Roxadustat had an acceptable tolerability profile.

SUBMITTER: Charytan C

PROVIDER: S-EPMC8258588 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Renal anemia of diabetic kidney disease (DKD) shows higher incidence rate, earlier onset and higher severity than other chronic kidney disease (CKD). Roxadustat, an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor, improves CKD anemia. This retrospective cohort study evaluates if Roxadustat could effectively treat DKD anemia. DKD anemia patients treated with either Roxadustat or erythropoietin (EPO) for 3 months in two hospitals were enrolled. EPO group were matched 1:1 to Roxadustat group based on age, gender and baseline Hb. Baseline data include age, sex, dialysis, height, weight, hemoglobin (Hb), hematocrit (Hct), serum albumin (ALB), serum creatinine (Scr), eGFR, C-reactive protein (CRP), and intact parathyroid hormone (iPTH). Primary and secondary outcomes were change of Hb (ΔHb) and Hct (ΔHct), Hb response rate and Hb qualified rate. Sensitivity analyses were performed and the effect size were calculated. No significant differences were observed in body mass index (BMI), Scr, eGFR, Hct, CRP, and dialysis between the 2 groups (61 subjects each). ALB, iPTH, and DKD stage differed between the 2 groups. After 3-month treatment, Roxadustat significantly increased patients' Hb and Hct. Although ΔHb and ΔHct of the Roxadustat group was higher than those of EPO group, difference in the least-square mean changes (95% CI) were 4.9 (-2.4, 12.1) and 1.2 (-1.1, 3.4), while Cohen's d were 0.18 and 0.14, suggesting that Roxadustat's ability to increase Hb within 3-month was similar to EPO. 78.7% and 54.1% of the patients responded to anti-anemia therapy in the Roxadustat and EPO group, respectively. Logistic regression analysis showed the Hb response rate of Roxadustat was 3.30 (1.20, 9.94) times higher than that of EPO. Subgroup analysis suggested that Roxadustat might have better efficacy in treating patients in the advanced stage, with high CRP and iPTH, and low ALB levels. In DKD patients, Roxadustat improves renal anemia. Effect of Roxadustat is similar to that of EPO.

Project description:IntroductionRoxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD). This European, phase 3, randomized, open-label, active-controlled study investigated efficacy and safety of roxadustat in patients with end-stage kidney disease on dialysis for at least 4 months.MethodsPatients were randomized to switch from an erythropoiesis-stimulating agent (ESA) (epoetin alfa or darbepoetin alfa) to roxadustat three times/week or to continue their previous ESA. Roxadustat and ESA doses were adjusted to maintain hemoglobin within 10.0-12.0 g/dL during the treatment period (day 1 up to 52-104 weeks). Primary endpoints were hemoglobin change from baseline (CFB) to the average of weeks 28-36 without rescue therapy and hemoglobin CFB to the average of weeks 28-52 regardless of rescue therapy. Treatment-emergent adverse events (TEAEs) were assessed descriptively.ResultsOf 1081 screened patients, 836 were randomized and received treatment (roxadustat, n = 415; ESA, n = 421). The least squares means (95% CI) of the treatment difference (roxadustat - ESA) for hemoglobin CFB to weeks 28-36 (without rescue therapy) and CFB to weeks 28-52 (regardless of rescue therapy) were 0.235 (0.132, 0.339) g/dL and 0.171 (0.082, 0.261) g/dL, respectively, demonstrating non-inferiority of roxadustat to ESA (non-inferiority margin of - 0.75 g/dL). The proportions of patients who achieved target hemoglobin without rescue therapy during weeks 28-36 were 84.2% (roxadustat) and 82.4% (ESA). Roxadustat was superior to ESA in decreasing LDL cholesterol from baseline to the average of weeks 12-28. Serious TEAEs occurred in 50.7% (roxadustat) and 45.0% (ESA) of patients. Common TEAEs in both treatment groups included hypertension, arteriovenous fistula thrombosis, headache, and diarrhea.ConclusionRoxadustat was non-inferior to ESAs in maintaining hemoglobin levels in this cohort of patients with anemia of CKD on dialysis for at least 4 months who were previously treated with ESAs. Observed TEAEs were consistent with previous studies.