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

Abstract

BackgroundIron 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.MethodsThe 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.ResultsIron 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).ConclusionsIron 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.

Effects of Ferric Citrate in Patients with Nondialysis-Dependent CKD and Iron Deficiency Anemia

“…Studies comparing oral to IV iron in this population have generally found greater efficacy for IV iron. 17,18 However, to truly understand oral iron efficacy, it would require parallel group testing against placebo or, to a lesser extent, comparison to no iron treatment; few such studies exist in NDD-CKD. In contrast, among patients receiving hemodialysis, three randomized clinical trials found no demonstrable efficacy for oral iron.…”

How we diagnose and treat iron deficiency anemia

“…As with the other new formulations permitting a large (500-1,000 mg) dose in 15 min, iron isomaltoside has been shown to be safe and effective in chronic kidney disease, inflammatory bowel disease, chemotherapy induced anemia, and perioperatively [62][63][64][65].…”

Intravenous Versus Oral Iron Supplementation for the Treatment of Anemia in CKD: An Updated Systematic Review and Meta-analysis

“…Regarding sequence generation, 10 trials of patients with CKD stages 3 to 5 were of low risk of bias, 16,17,20,[22][23][24][25][26][27][28] whereas 3 were of unclear risk. 18,19,21 Seven trials of patients with CKD stage 5D were of low risk of sequence generation bias, 30-34,36,37 3 were of unclear risk, 29,35,38 and 1 was of high risk.…”