Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial

Kalra, P. R. et al. (2022) Intravenous ferric derisomaltose in patients with heart failure and iron deficiency in the UK (IRONMAN): an investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial. Lancet, 400(10369), pp. 2199-2209. (doi: 10.1016/S0140-6736(22)02083-9) (PMID:36347265)

[img] Text
282503.pdf - Published Version
Available under License Creative Commons Attribution.

617kB

Abstract

Background: For patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric carboxymaltose administration improves quality of life and exercise capacity in the short-term and reduces hospital admissions for heart failure up to 1 year. We aimed to evaluate the longer-term effects of intravenous ferric derisomaltose on cardiovascular events in patients with heart failure. Methods: IRONMAN was a prospective, randomised, open-label, blinded-endpoint trial done at 70 hospitals in the UK. Patients aged 18 years or older with heart failure (left ventricular ejection fraction ≤45%) and transferrin saturation less than 20% or serum ferritin less than 100 μg/L were eligible. Participants were randomly assigned (1:1) using a web-based system to intravenous ferric derisomaltose or usual care, stratified by recruitment context and trial site. The trial was open label, with masked adjudication of the outcomes. Intravenous ferric derisomaltose dose was determined by patient bodyweight and haemoglobin concentration. The primary outcome was recurrent hospital admissions for heart failure and cardiovascular death, assessed in all validly randomly assigned patients. Safety was assessed in all patients assigned to ferric derisomaltose who received at least one infusion and all patients assigned to usual care. A COVID-19 sensitivity analysis censoring follow-up on Sept 30, 2020, was prespecified. IRONMAN is registered with ClinicalTrials.gov, NCT02642562. Findings: Between Aug 25, 2016, and Oct 15, 2021, 1869 patients were screened for eligibility, of whom 1137 were randomly assigned to receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2·7 years (IQR 1·8–3·6). 336 primary endpoints (22·4 per 100 patient-years) occurred in the ferric derisomaltose group and 411 (27·5 per 100 patient-years) occurred in the usual care group (rate ratio [RR] 0·82 [95% CI 0·66 to 1·02]; p=0·070). In the COVID-19 analysis, 210 primary endpoints (22·3 per 100 patient-years) occurred in the ferric derisomaltose group compared with 280 (29·3 per 100 patient-years) in the usual care group (RR 0·76 [95% CI 0·58 to 1·00]; p=0·047). No between-group differences in deaths or hospitalisations due to infections were observed. Fewer patients in the ferric derisomaltose group had cardiac serious adverse events (200 [36%]) than in the usual care group (243 [43%]; difference –7·00% [95% CI –12·69 to –1·32]; p=0·016). Interpretation: For a broad range of patients with heart failure, reduced left ventricular ejection fraction and iron deficiency, intravenous ferric derisomaltose administration was associated with a lower risk of hospital admissions for heart failure and cardiovascular death, further supporting the benefit of iron repletion in this population. Funding: British Heart Foundation and Pharmacosmos.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Squire, Dr Iain and Graham, Dr Fraser and Petrie, Professor Mark and Kalra, Professor Paul and Robertson, Mrs Michele and Lang, Dr Ninian and Cleland, Professor John and Thomson, Miss Elizabeth and Ford, Professor Ian and Pellicori, Dr Pierpaolo
Authors: Kalra, P. R., Cleland, J. G.F., Petrie, M. C., Thomson, E. A., Kalra, P. A., Squire, I. B., Ahmed, F. Z., Al-Mohammad, A., Cowburn, P. J., Foley, P. W.X., Graham, F. J., Japp, A. G., Lane, R. E., Lang, N. N., Ludman, A. J., Macdougall, I. C., Pellicori, P., Ray, R., Robertson, M., Seed, A., and Ford, I.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:Lancet
Publisher:The Lancet Publishing Group
ISSN:0140-6736
ISSN (Online):1474-547X
Published Online:05 November 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Lancet 400(10369): 2199-2209
Publisher Policy:Reproduced under a Creative Commons License
Related URLs:

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172792Intravenous iron treatment in patients with heart failure and iron deficiency: a multicentre UK study (IRONMAN)Ian FordBritish Heart Foundation (BHF)CS/15/1/31175HW - Robertson Centre
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science