The safety and efficacy of a single dose of intravenous ferric carboxymaltose in patients undergoing hemodialysis: a multicenter, single-arm, open-label, clinical trial

Iron deficiency anemia is common among patients undergoing maintenance hemodialysis (HD), due to increased blood loss and reduced absorption. Numerous clinical guidelines recommend administering iron intravenously to adequately correct the condition. In Japan, the guideline describes intravenous saccharated ferric oxide 40 mg administered to HD patients at the end of a dialysis session once weekly or once every two weeks. A cycle consists of 13 administrations, with efficacy and iron status evaluated. Recently, ferric carboxymaltose (FCM), a large-dose intravenous iron agent, has become available in Japan for treating iron deficiency anemia. However, the evidence on the safety and efficacy of FCM in Japanese HD patients, who generally have lower ferritin levels compared with patients in other countries, is still limited. This study primarily investigated the safety and efficacy of FCM in patients with maintenance HD.

We conducted a 12-weeks, multicenter, prospective, open-label, single-arm trial (jRCTs051230025) to investigate the efficacy and safety of a single 500 mg dose of FCM in 30 Japanese HD patients with anemia (Hb <10 g/dL) and iron deficiency (ferritin <100 ng/mL or transferrin saturation (TSAT) <20%). Following administration of the FCM, no iron supplementation was permitted during the 12-weeks study period. The primary efficacy endpoint was the changes in hemoglobin (Hb) levels from baseline to week 4 after intravenous injection. The secondary objectives were the changes in Hb, ferritin, TSAT, 8-hydroxy-2′-deoxyguanosine (8-OHdG), hepcidin, intact fibroblast growth factor-23 (FGF23), serum phosphate, and quality of life (QOL; SF-36 v2 and EQ-5D-5L) over 12 weeks. We also investigated any adverse events (AEs), and safety parameters defined as ferritin ≥500 ng/mL or TSAT ≥50%.

All patients (mean age 70.6 ± 12.6 years, 56.7% male) completed the study. Hb levels significantly increased from baseline to week 4 (Up to 0.50 g/dL; 95% confidence interval (CI): 0.18–0.82; p = 0.003), and up to 0.70 g/dL at week 12 (95% CI: 0.39–1.01; p <0.001). These effects were observed across categories of sex, age, diabetes, BMI, and baseline iron status. Ferritin, 8-OHdG, hepcidin, and intact FGF23 levels peaked at week 1, whereas TSAT peaked at week 2. Thereafter, these markers gradually decreased, returning to baseline levels until week 12, while serum phosphate levels remained unchanged over the study period. Among the SF-36 domains, the scores for vitality and mental health increased significantly at weeks 4, 8 and 12 compared with baseline. 16 patients (53.3%) experienced the elevation of ferritin ≥500 ng/mL by week 8. Of these, 15 patients decreased below 500 ng/mL thereafter. 2 patients (6.7%) had TSAT ≥50% at week 1. One decreased below 50% of TSAT after two weeks.

A single 500 mg dose of FCM was well tolerated and effective in increasing Hb levels and iron parameters in Japanese HD patients with iron deficiency anemia, without serious adverse effects. Further, larger, long-term clinical trials are warranted to confirm the safety and efficacy of repeated supplementation with FCM.