136 Risk of infection with ferric derisomaltose compared to standard of care in patients with heart failure and iron deficiency in the uk: a prespecified analysis of the ironman trial

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Introduction Recent results from the IRONMAN trial add to previous data and demonstrate that correction of iron deficiency in patients with heart failure, with high dose IV iron can improve quality of life, and reduce the risk of heart failure hospitalisation (by around 25% in meta-analysis). Yet there are theoretical risks that IV iron administration may increase the risk from bacterial infection. A meta-analysis in 2021 (across many clinical indications) suggested an excess risk of infections with IV iron but noted most trials did not pre-specify infection as an end point, with risk of reporting bias. To answer this important question hospitalisation for infection or death due to infection were pre-specified safety endpoints in IRONMAN. Methods IRONMAN was a prospective, randomised open-label, blinded endpoint (PROBE) event-driven trial of IV ferric derisomaltose (FDI) and usual care versus usual care alone in patients with heart failure (LVEF ≤45% ) and iron deficiency (ferritin <100 µg/L and/or TSAT <20%, provided ferritin ≤400 µg/L). Patients were enrolled if they had a current or recent hospitalisation for heart failure or elevated natriuretic peptide plasma concentration. Every four months, IV iron was administered if either ferritin was <100 µg/L or TSAT was <25% (provided ferritin ≤400 µg/L). All hospitalisations and deaths were adjudicated blindly. Given that a large part of the trial was conducted during the COVID-19 pandemic, we also evaluated COVID-19 related SAEs. Results 1137 patients (26.4% women) with median (IQR) age 73 (63 to 79) years were recruited by the Ironman Study Group between Aug 2016 and Oct 2021 across 70 UK sites. Median (IQR) follow-up was 2·7 (1·8 to 3·6) years. 97% of patients consented to record linkage to national databases of deaths and hospital discharge summaries, thereby ensuring investigators were aware of all potential events. There were a similar number of hospitalisations due to infection for those assigned to ferric derisomaltose (175) and usual care (213) (p = 0.16) and infection related death (34 and 28, respectively, p = 0.43). When considering first events of hospitalisation for infection or infection death there were 120 (21.1%) events for those randomised to IV FDI and 146 (25.7%) for the usual care arm (figure). There were fewer patients with COVID related SAEs in those randomised to IV FDI (12) as compared with usual care (30), HR (95% CI) 0.40 (0.20, 0.78). p=0.007. For deaths attributed to COVID-19, 4 were seen in the IV FDI arm and 8 in the usual care arm: HR 0.51 (0.15, 1.68) p=0.27. Conclusions There was no excess risk of infection related hospitalisation or death in patients receiving IV ferric derisomaltose. Fewer COVID-19 related SAEs were seen in patients receiving IV FDI. Given that iron plays an important role in the T and B cell response to vaccination, further analysis needs to be done in this area. Conflict of Interest Honorarium for education from Pharmocosmos

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