Safety and efficacy of iron isomaltoside 1000/ferric derisomaltose versus iron sucrose in patients with chronic kidney disease: the FERWON-NEPHRO randomized, open-label, comparative trial

Nephrol Dial Transplant. 2021 Jan 1;36(1):111-120. doi: 10.1093/ndt/gfaa011.

Abstract

Background: The optimal intravenous (IV) iron would allow safe correction of iron deficiency at a single infusion over a short time. The FERWON-NEPHRO trial evaluated the safety and efficacy of iron isomaltoside 1000/ferric derisomaltose (IIM) in patients with non-dialysis-dependent chronic kidney disease and iron deficiency anaemia.

Methods: In this randomized, open-label and multi-centre trial conducted in the USA, patients were randomized 2:1 to a single dose of 1000 mg IIM or iron sucrose (IS) administered as 200 mg IV injections up to five times within a 2-week period. The co-primary endpoints were serious or severe hypersensitivity reactions and change in haemoglobin (Hb) from baseline to Week 8. Secondary endpoints included incidence of composite cardiovascular adverse events (AEs).

Results: A total of 1538 patients were enrolled (mean estimated glomerular filtration rate 35.5 mL/min/1.73 m2). The co-primary safety objective was met based on no significant difference in the incidence of serious or severe hypersensitivity reactions in the IIM and IS groups [0.3% versus 0%; risk difference: 0.29% (95% confidence interval: -0.19; 0.77; P > 0.05)]. Incidence of composite cardiovascular AEs was significantly lower in the IIM versus IS group (4.1% versus 6.9%; P = 0.025). Compared with IS, IIM led to a more pronounced increase in Hb during the first 4 weeks (P ≤ 0.021), and change in Hb to Week 8 showed non-inferiority, confirming that the co-primary efficacy objective was met.

Conclusions: Compared with multiple doses of IS, a single dose of IIM induced a non-inferior 8-week haematological response, comparably low rates of hypersensitivity reactions, and a significantly lower incidence of composite cardiovascular AEs.

Trial registration: ClinicalTrials.gov NCT02940860.

Keywords: ferric derisomaltose; iron deficiency anaemia; iron isomaltoside 1000; iron treatment.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Iron-Deficiency / drug therapy*
  • Anemia, Iron-Deficiency / etiology
  • Anemia, Iron-Deficiency / pathology
  • Disaccharides / administration & dosage*
  • Female
  • Ferric Compounds / administration & dosage*
  • Ferric Oxide, Saccharated / administration & dosage*
  • Hematinics / administration & dosage*
  • Hemoglobins / analysis
  • Humans
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Insufficiency, Chronic / complications*
  • Time Factors

Substances

  • Disaccharides
  • Ferric Compounds
  • Hematinics
  • Hemoglobins
  • iron isomaltoside 1000
  • Ferric Oxide, Saccharated

Associated data

  • ClinicalTrials.gov/NCT02940860