A randomized controlled trial comparing intravenous ferric carboxymaltose with oral iron for treatment of iron deficiency anaemia of non-dialysis-dependent chronic kidney disease patients

Abstract

Background: Iron deficiency is a common cause of anaemia and hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) in non-dialysis-dependent chronic kidney disease (ND-CKD) patients. Current intravenous iron agents cannot be administered in a single high dose because of adverse effects. Ferric carboxymaltose, a non-dextran parenteral iron preparation, can be rapidly administered in high doses.

Methods: This open-label trial randomized 255 subjects with glomerular filtration rates ≤ 45 mL/min/1.73 m(2), haemoglobin ≤ 11 g/dL, transferrin saturation ≤ 25%, ferritin ≤ 300 ng/mL, and stable ESA dose to either intravenous ferric carboxymaltose 1000 mg over 15 min (with up to two additional doses of 500 mg at 2-week intervals) or oral ferrous sulphate 325 mg thrice daily for a total of 195 mg elemental iron daily for 56 days.

Results: In the modified intent-to-treat population, the proportion of subjects achieving a haemoglobin increase ≥ 1 g/dL at any time was 60.4% with ferric carboxymaltose and 34.7% with oral iron (P < 0.001). At Day 42, mean increase in haemoglobin was 0.95 ± 1.12 vs 0.50 ± 1.23 g/dL (P = 0.005), mean increase in ferritin was 432 ± 189 ng/mL vs 18 ± 45 ng/mL (P < 0.001) and mean increase in transferrin saturation was 13.6 ± 11.9% vs 6.1 ± 8.1% (P < 0.001). Treatment-related adverse events were significantly fewer with ferric carboxymaltose than with oral iron (2.7% and 26.2%, respectively; P < 0.0001).

Conclusions: We conclude that 1000 mg ferric carboxymaltose can be rapidly administered, is more effective and is better tolerated than oral iron for treatment of iron deficiency in ND-CKD patients.

Fig. 1

Patient disposition.

Fig. 2

Percent of subjects (mITT population) achieving Hb ≥ 1 g/dL at any study time point (last observation carried forward). Hb, haemoglobin; mITT, modified intention-to-treat.

Fig. 3

Mean (SE) for (A) haemoglobin (g/dL), (B) ferritin (ng/mL) and (C) TSAT (%) values by treatment group over time. FCM, ferric carboxymaltose; TSAT, transferrin saturation. *Significantly higher compared with baseline value in the FCM group. P-values are from unpaired two-sample t-tests, assuming equal variances for differences in change from baseline, and are for differences between the FCM and oral iron groups at various study points.