FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia

Abstract

Background: The optimal iron therapy regimen in patients with non-dialysis-dependent chronic kidney disease (CKD) is unknown.

Methods: Ferinject® assessment in patients with Iron deficiency anaemia and Non-Dialysis-dependent Chronic Kidney Disease (FIND-CKD) was a 56-week, open-label, multicentre, prospective and randomized study of 626 patients with non-dialysis-dependent CKD, anaemia and iron deficiency not receiving erythropoiesis-stimulating agents (ESAs). Patients were randomized (1:1:2) to intravenous (IV) ferric carboxymaltose (FCM), targeting a higher (400-600 µg/L) or lower (100-200 µg/L) ferritin or oral iron therapy. The primary end point was time to initiation of other anaemia management (ESA, other iron therapy or blood transfusion) or haemoglobin (Hb) trigger of two consecutive values <10 g/dL during Weeks 8-52.

Results: The primary end point occurred in 36 patients (23.5%), 49 patients (32.2%) and 98 patients (31.8%) in the high-ferritin FCM, low-ferritin FCM and oral iron groups, respectively [hazard ratio (HR): 0.65; 95% confidence interval (CI): 0.44-0.95; P = 0.026 for high-ferritin FCM versus oral iron]. The increase in Hb was greater with high-ferritin FCM versus oral iron (P = 0.014) and a greater proportion of patients achieved an Hb increase ≥1 g/dL with high-ferritin FCM versus oral iron (HR: 2.04; 95% CI: 1.52-2.72; P < 0.001). Rates of adverse events and serious adverse events were similar in all groups.

Conclusions: Compared with oral iron, IV FCM targeting a ferritin of 400-600 µg/L quickly reached and maintained Hb level, and delayed and/or reduced the need for other anaemia management including ESAs. Within the limitations of this trial, no renal toxicity was observed, with no difference in cardiovascular or infectious events.

Clinicaltrialsgov number: NCT00994318.

Keywords: anaemia; chronic kidney disease.

© The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA.

Figures

FIGURE 1:

Enrolment and outcomes. The ITT population comprised all patients who received at least one dose of randomized treatment, or according to the protocol were not treated due to ferritin level, and attended at least one post-baseline visit. The safety population included all patients who received at least one dose of randomized treatment, and included 154 patients in the high-ferritin FCM group, 150 patients in the low-ferritin FCM group and 312 patients in the oral iron group. Two patients randomized to the low-ferritin FCM group met the eligibility requirements at screening but did not require FCM during the study according to the protocol-specified criteria for ferritin. These two patients were included in the ITT population but excluded from the safety population.

FIGURE 2:

(A) Time to initiation of other anaemia management or Hb trigger (Kaplan–Meier estimates) and LS mean locally measured observed values over time for (B) Hb (C) ferritin and (D) TSAT according to treatment group (ITT population). Measurements of Hb, ferritin and TSAT were included up to the point at which other anaemia therapy was initiated (with or without cessation of randomized study drug) and/or the patient discontinued the study. BL, baseline; FCM, ferric carboxymaltose.