A randomized trial of iron isomaltoside 1000 versus oral iron in non-dialysis-dependent chronic kidney disease patients with anaemia

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2016-04, Vol.31 (4), p.646-655
• Main Authors: Kalra, Philip A, Bhandari, Sunil, Saxena, Sanjiv, Agarwal, Dhananjai, Wirtz, Georg, Kletzmayr, Josef, Thomsen, Lars L, Coyne, Daniel W
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Anemia, Iron-Deficiency - drug therapy; Anemia, Iron-Deficiency - etiology; CLINICAL SCIENCE; Disaccharides - therapeutic use; Female; Ferric Compounds - therapeutic use; Hemoglobins - analysis; Humans; Iron - therapeutic use; Male; Middle Aged; Prospective Studies; Renal Dialysis; Renal Insufficiency, Chronic - complications; Time Factors; Treatment Outcome; Young Adult
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfv293

Iron deficiency anaemia is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) and is often treated with oral or intravenous (IV) iron therapy. This trial compared the efficacy and safety of IV iron isomaltoside 1000 (Monofer®) and oral iron in NDD-CKD patients with renal-related anaemia. The trial was a Phase III open-label, comparative, multicentre, non-inferiority trial conducted in 351 iron-deficient NDD-CKD patients, randomized 2:1 to either iron isomaltoside 1000 (Group A) or iron sulphate administered as 100 mg elemental oral iron twice daily (200 mg daily) for 8 weeks (Group B). The patients in Group A were randomized into A1 (infusion of max. 1000 mg single doses over 15 min) and A2 (bolus injections of 500 mg over 2 min). A modified Ganzoni formula was used to calculate IV iron need. The primary end point was change in haemoglobin concentrations from baseline to Week 4. Iron isomaltoside 1000 was both non-inferior to oral iron at Week 4 (P < 0.001) and sustained a superior increase in haemoglobin from Week 3 until the end of the study at Week 8 (P = 0.009 at Week 3). The haemoglobin response was more pronounced with iron isomaltoside 1000 doses ≥1000 mg (P < 0.05). Serum-ferritin and transferrin saturation concentrations were also significantly increased with IV iron. Adverse drug reactions were observed in 10.5% in the iron isomaltoside 1000 group and 10.3% in the oral iron group. More patients treated with oral iron sulphate withdrew from the study due to adverse events (4.3 versus 0.9%, P = 0.2). Iron isomaltoside 1000 was more efficacious than oral iron for increase in haemoglobin and proved to be well tolerated at the tested dose levels in NDD-CKD patients.