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 PR

Published in The Lancet

Methodology

Investigator-initiated, prospective, randomised, open-label, blinded-endpoint trial (NCT02642562) at 70 UK hospitals, August 2016 to October 2021; adults with heart failure and left ventricular ejection fraction 45% or below plus transferrin saturation under 20% or ferritin under 100 micrograms/L randomised 1:1 to intravenous ferric derisomaltose (dosed by bodyweight and haemoglobin) or usual care; primary outcome recurrent heart failure admissions and cardiovascular death, with a prespecified COVID-19 sensitivity analysis.

Key Findings

IRONMAN randomised 1,137 UK patients with heart failure (ejection fraction 45% or less) and iron deficiency to intravenous ferric derisomaltose (569) or usual care (568), with median follow-up of 2.7 years. The primary endpoint of recurrent heart failure hospital admissions plus cardiovascular death occurred at 22.4 per 100 patient-years with iron versus 27.5 with usual care (rate ratio 0.82, 95% CI 0.66 to 1.02, p = 0.070) — a favourable trend that fell just short of significance. In the prespecified COVID-19 sensitivity analysis the difference reached significance (RR 0.76, 95% CI 0.58 to 1.00, p = 0.047). Fewer patients on iron had cardiac serious adverse events (36% vs 43%, difference -7.00%, 95% CI -12.69 to -1.32, p = 0.016), with no difference in deaths or infection hospitalisations.

Conclusions

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.

Limitations

The primary endpoint did not reach statistical significance and the trial was open-label (though endpoints were adjudicated blind), so the positive reading depends on a sensitivity analysis censoring the COVID-19 period; this used intravenous iron under medical supervision, which does not translate to oral iron supplements.