Anemia Therapy in Patients With Infective Endocarditis

Summary

Infective endocarditis (IE) is a bacterial infection of the heart valves, inserted material or surrounding struc-tures and is associated with a high morbidity and mortality. In patients with IE, anemia is considered to result from the underlying infection, prolonged sustained inflammatory response due to the often slow natural course of the disease, and coexisting comorbidities. Previous studies have found that moderate to severe anemia is associated with a markedly higher risk of mortality in the 6-months recovery phase following treatment for IE. In many cardiac patients and patients with chronic inflammation, randomized trials have shown benefit of treatment of anemia with adjunctive therapy i.e., vitamins (vitamin B12/folic acid), intravenous iron, and erythropoiesis stimulating agents in alleviating anemia, without increased risk of infection. Despite these findings, anemia screening and management are not addressed in current endocarditis guidelines. Thus, in patients with IE and anemia, adjunctive treatment of the anemia might be beneficial for recovery and improve outcomes. The aim of POET-IRON is to assess the efficacy of adjunctive anemia treatment in patients with IE, using intravenous iron supplementation, erythropoietin-stimulated erythropoiesis, and dietary optimization including vitamins if necessary, and its effect on hemoglobin levels compared to standard care. The investigators hypothesize that this intervention is safe and will increase hemoglobin concentration, thereby alleviating symptoms of anemia and improving clinical outcomes through enhanced oxygen-carrying capacity, tissue oxygenation, and functional status.

Timeline

Start

2026-05-15

Primary completion

2028-04

Completion

2028-08

Publications

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• Background Iversen K, Ihlemann N, Gill SU, Madsen T, Elming H, Jensen KT, Bruun NE, Hofsten DE, Fursted K, Christensen JJ, Schultz M, Klein CF, Fosboll EL, Rosenvinge F, Schonheyder HC, Kober L, Torp-Pedersen C, Helweg-Larsen J, Tonder N, Moser C, Bundgaard H. Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med. 2019 Jan 31;380(5):415-424. doi: 10.1056/NEJMoa1808312. Epub 2018 Aug 28.
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• Background Erichsen P, Gislason GH, Bruun NE. The increasing incidence of infective endocarditis in Denmark, 1994-2011. Eur J Intern Med. 2016 Nov;35:95-99. doi: 10.1016/j.ejim.2016.05.021. Epub 2016 Jun 21.
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• Background Delgado V, Ajmone Marsan N, de Waha S, Bonaros N, Brida M, Burri H, Caselli S, Doenst T, Ederhy S, Erba PA, Foldager D, Fosbol EL, Kovac J, Mestres CA, Miller OI, Miro JM, Pazdernik M, Pizzi MN, Quintana E, Rasmussen TB, Ristic AD, Rodes-Cabau J, Sionis A, Zuhlke LJ, Borger MA; ESC Scientific Document Group. 2023 ESC Guidelines for the management of endocarditis. Eur Heart J. 2023 Oct 14;44(39):3948-4042. doi: 10.1093/eurheartj/ehad193. No abstract available.
• Background Cleland JGF, Kalra PA, Pellicori P, Graham FJ, Foley PWX, Squire IB, Cowburn PJ, Seed A, Clark AL, Szwejkowski B, Banerjee P, Cooke J, Francis M, Clifford P, Wong A, Petrie C, McMurray JJV, Thomson EA, Wetherall K, Robertson M, Ford I, Kalra PR; IRONMAN Study Group. Intravenous iron for heart failure, iron deficiency definitions, and clinical response: the IRONMAN trial. Eur Heart J. 2024 Apr 21;45(16):1410-1426. doi: 10.1093/eurheartj/ehae086.
• Background Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM, Tang WHW, LaRue SJ, Redfield MM, Semigran MJ, Givertz MM, Van Buren P, Whellan D, Anstrom KJ, Shah MR, Desvigne-Nickens P, Butler J, Braunwald E; NHLBI Heart Failure Clinical Research Network. Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial. JAMA. 2017 May 16;317(19):1958-1966. doi: 10.1001/jama.2017.5427.
• Background Beavers CJ, Ambrosy AP, Butler J, Davidson BT, Gale SE, Pina IL, Mastoris I, Reza N, Mentz RJ, Lewis GD. Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America. J Card Fail. 2023 Jul;29(7):1059-1077. doi: 10.1016/j.cardfail.2023.03.025. Epub 2023 May 1.
• Background Ponikowski P, Kirwan BA, Anker SD, McDonagh T, Dorobantu M, Drozdz J, Fabien V, Filippatos G, Gohring UM, Keren A, Khintibidze I, Kragten H, Martinez FA, Metra M, Milicic D, Nicolau JC, Ohlsson M, Parkhomenko A, Pascual-Figal DA, Ruschitzka F, Sim D, Skouri H, van der Meer P, Lewis BS, Comin-Colet J, von Haehling S, Cohen-Solal A, Danchin N, Doehner W, Dargie HJ, Motro M, Butler J, Friede T, Jensen KH, Pocock S, Jankowska EA; AFFIRM-AHF investigators. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020 Dec 12;396(10266):1895-1904. doi: 10.1016/S0140-6736(20)32339-4. Epub 2020 Nov 13.
• Background Pries-Heje MM, Hasselbalch RB, Wiingaard C, Fosbol EL, Glenthoj AB, Ihlemann N, Gill SUA, Christiansen U, Elming H, Bruun NE, Povlsen JA, Helweg-Larsen J, Schultz M, Ostergaard L, Fursted K, Christensen JJ, Rosenvinge F, Kober L, Tonder N, Moser C, Iversen K, Bundgaard H. Severity of anaemia and association with all-cause mortality in patients with medically managed left-sided endocarditis. Heart. 2022 May 12;108(11):882-888. doi: 10.1136/heartjnl-2021-319637.
• Background Breel JS, Bozic C, Alberts T, Strypet M, Mansvelder FJ, Schober P, Kamp O, Boekholdt SM, Klautz RJM, Muller MCA, van der Vaart TW, Tanis W, van der Stoel M, Hollmann MW, Eberl S, Hermanns H; Dutch Perioperative Infective Endocarditis Research Group; Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration. Anaemia and blood transfusion in cardiac surgery with infective endocarditis. Heart. 2026 Jan 29:heartjnl-2025-326424. doi: 10.1136/heartjnl-2025-326424. Online ahead of print.

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