Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial

Sigismond Lasocki (1, 2) , Pierre Asfar (1, 2) , Samir Jaber (3, 4) , Martine Ferrandiere (5, 6) , Thomas Kerforne (7, 8) , Karim Asehnoune (9, 10) , Philippe Montravers (11, 12) , Philippe Seguin (13, 14) , Katell Peoc’h (15, 16, 17) , Soizic Gergaud (1, 2) , Nicolas Nagot (18, 4) , Thibaud Lefebvre (15) , Sylvain Lehmann (19, 18)

1 CHU Angers - Centre Hospitalier Universitaire d'Angers
2 UA - Université d'Angers
3 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
4 UM - Université de Montpellier
5 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
6 UT - Université de Tours
7 CHU de Poitiers - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
8 UP - Université de Poitiers = University of Poitiers
9 CHU Nantes - Centre Hospitalier Universitaire de Nantes
10 Nantes Univ - Nantes Université
11 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
12 UPD7 - Université Paris Diderot - Paris 7
13 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Ponchaillou]
14 UR - Université de Rennes
15 CRI (UMR_S_1149 / ERL_8252 / U1149) - Centre de recherche sur l'Inflammation
16 Hôpital Louis Mourier - AP-HP [Colombes]
17 Labex Gr-Ex - Laboratoire d'Excellence : Biogenèse et pathologies du globule rouge
18 CHU Montpellier
19 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)

Background : Anemia is a significant problem in patients on ICU. Its commonest cause, iron deficiency (ID), is difficult to diagnosed in the context of inflammation. Hepcidin is a new marker of ID. We aimed to assess whether hepcidin levels would accurately guide treatment of ID in critically ill anemic patients after a prolonged ICU stay and affect the post-ICU outcomes. Methods : In a controlled, single-blinded, multicenter study, anemic (WHO definition) critically ill patients with an ICU stay ≥5 days were randomized when discharge was expected to either intervention by hepcidin treatment protocol or control. In the intervention arm patients were treated with intravenous iron (1g of ferric carboxymaltose) when hepcidin was <20 μg/l and with intravenous iron and erythropoietin for 20≤ hepcidin <41 μg/l. Control patients were treated according to standard care (hepcidin quantification remained blinded). Primary endpoint was the number of days spent in hospital 90 days after ICU discharge (post-ICU LOS). Secondary endpoints were day 15 anemia, day 30 fatigue and day 90 mortality. Results : Of 405 randomized patients, 399 were analyzed (201 in intervention and 198 in control arm). 220(55%) had ID at discharge (i.e. an hepcidin <41 μg/l). Primary endpoint was not different (medians(IQR) post-ICU LOS 33(13;90) vs 33(11;90) days for intervention and control respectively, median difference -1(-3;1) days, p=0.78). D90 mortality was significantly lower in the intervention arm (16(8%) vs 33(16.6%) deaths, absolute risk difference -8.7 (-15.1 to -2.3)%, p=0.008). Conclusion : Treatment of ID diagnosed according to hepcidin levels did not reduce the post-ICU LOS, but may reduce the long-term mortality in critically ill patients about to be discharged after a prolonged stay. Trial Registration : www.clinicaltrial.gov NCT02276690 (October 28, 2014; Retrospectively registered)

Mots clés: Anemia; Critically ill; Erythropoietin; Hepcidin; Iron (treatment); Iron deficiency; Length of stay; Mortality

Domaines: Sciences du Vivant [q-bio]

Sigismond Lasocki, Pierre Asfar, Samir Jaber, Martine Ferrandiere, Thomas Kerforne, et al.. Interest of Treating Iron Deficiency, Diagnosed According to Hepcidin Quantification, on Outcomes After a Prolonged Icu Stay Compared to Standard Care: A Multicenter, Randomized, Single-blinded Trial. 2022. ⟨hal-02941084⟩