Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial

Abstract

Background. The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods. FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400–600 µg/L) or lower (100–200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results. The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions. These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD.

Randomised clinical trial: intravenous vs oral iron for the treatment of anaemia after acute gastrointestinal bleeding

“…The results of our study showing the superiority of FCM over oral FeSulf for the treatment and resolution of anaemia secondary to acute GIB is in line with evidence for the efficacy and safety of FCM in a wide range of conditions such as chronic kidney disease, colorectal cancer, inflammatory bowel disease, uterine bleeding and postpartum anaemia . The results are also consistent with a meta‐analysis that assessed studies using different iv iron preparation to treat IDA in patients with different conditions and concluded that although all iv and oral formulations could correct IDA, FCM was the superior treatment …”

The available intravenous iron formulations: History, efficacy, and toxicology

“…The trial also showed the group receiving higher doses FCM had a significantly greater time lapse before other anemia therapies were required, as well as an earlier and larger increase in hemoglobin. No significant safety concerns were noted, and only 2 minor hypersensitivity reactions were reported, neither of which required hospitalization …”

Positive Iron Balance in Chronic Kidney Disease: How Much is Too Much and How to Tell?

“…A pair of randomized trials examining the safety and efficacy of oral vs IV iron formulations (REVOKE and FIND-CKD) has demonstrated conflicting results [47, 48]. Whereas REVOKE demonstrated a higher risk of serious adverse events, cardiovascular serious adverse events, and infection resulting in hospitalization among non-HD patients receiving IV iron (vs. oral iron), FIND-CKD did not identify a safety signal among patients receiving low (targeting a ferritin of 100–200 μg/L) or high (targeting a ferritin of 400–600 μg/L) doses of IV iron as compared to patients receiving only oral iron or the subgroup of patients that attained a ferritin of 800 μg/L or greater [47-49]. The differences between these 2 studies and potential explanations for their findings have been discussed previously [50, 51].…”