A prospective observational study of iron isomaltoside in haemodialysis patients with chronic kidney disease treated for iron deficiency (DINO)

Ashraf I Mikhail, Staffan Schön, Sylvia Simon, Christopher Brown, Jörgen B A Hegbrant, Gert Jensen, Jason Moore, Lennart D I Lundberg, Ashraf I Mikhail, Staffan Schön, Sylvia Simon, Christopher Brown, Jörgen B A Hegbrant, Gert Jensen, Jason Moore, Lennart D I Lundberg

Abstract

Background: Iron deficiency is frequent in haemodialysis (HD) patients with chronic kidney disease (CKD), and intravenous iron is an established therapy for these patients. This study assessed treatment routine, effectiveness, and safety of iron isomaltoside (IIM) 5% (Diafer®) in a HD cohort.

Methods: This prospective observational study included 198 HD patients converted from iron sucrose (IS) and treated with IIM according to product label and clinical routine. Data for IIM were compared to historic data for IS in 3-month intervals. The primary endpoint was to show non-inferiority for IIM versus IS in haemoglobin (Hb) maintenance.

Results: Most patients (> 60%) followed a fixed low-dose iron treatment protocol. Three minutes were required for preparation and administration of IIM. Erythropoiesis-stimulating agent (ESA) was used in > 80% of patients during both IIM and IS phases. The maintenance of Hb was similar with both iron drugs; the mean Hb level was 11 g/dL, and the mean change of 0.3 g/dL (95% confidence interval: 0.1, 0.5) for IIM 0-3 months compared to IS demonstrated non-inferiority. Nine adverse drug reactions were reported in 2% of patients administered IIM. All patients had uneventful recoveries. The frequency of metallic taste was higher with IS compared to IIM (34% versus 0.5%, p < 0.0001).

Conclusions: IIM is effective and well tolerated by CKD patients on HD. IIM was non-inferior to IS in maintenance of Hb, and had similar ESA requirements. The fast-push injection of IIM may enable logistical benefits in clinical practice, and the low frequency of metallic taste contributes to patient convenience.

Trial registration: ClinicalTrials.gov identifier NCT02301026, study registered November 25, 2014.

Keywords: Chronic kidney disease; Haemodialysis; Haemoglobin; Iron deficiency; Iron isomaltoside.

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the regional ethics committees in Sweden (EPN Lund; 2014/306) and in the UK (East of Scotland Research Ethics Service; 14/ES/1075), and was performed in accordance with the Declaration of Helsinki. All participants provided written informed consent prior to inclusion into the study.

Consent for publication

Not applicable.

Competing interests

SSi is employed by Pharmacosmos A/S, Denmark. The other authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Study design. IIM = iron isomaltoside; IS = iron sucrose
Fig. 2
Fig. 2
Patient flow diagram (based on CONSORT 2010). Hb = haemoglobin; IIM = iron isomaltoside; IS = iron sucrose
Fig. 3
Fig. 3
Mean Hb changes for the IIM prospective phases versus the IS retrospective phase. Non-inferiority was achieved for the primary endpoint comparison of IIM 0–3 months to IS where the lower limit of the 95% CI was above the margin of − 0.15 g/dL. CI = confidence interval; Hb = haemoglobin; IIM = iron isomaltoside; IS = iron sucrose
Fig. 4
Fig. 4
Percent distribution of all Hb values across Hb ranges (a), percent patient distribution across ferritin ranges based on individual mean values (b), and percent patient distribution across TSAT ranges based on individual mean values (c). The maintenance of Hb and iron parameters with IIM compared to IS treatment was similar. Hb = haemoglobin; IIM = iron isomaltoside; IS = iron sucrose; TSAT = transferrin saturation

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