Use of Epoetin Alfa and Iron Derisomaltose in Treatment of Anemia in Patients With Sepsis or Septic Shock: a Randomized Controlled Trial

Summary

Background Up to 66% of have anemia at the admission to the intensive care unit. This number increases to 95% after 72 hours of hospitalization in the intensive care unit due to illness and iatrogenic blood loss. Anemia worsens tissue oxygenation, especially in patietns with sepsis or septic shock, who already have blood flow issues. Instead of giving blood transfusions, which can have side effects, we aim to address the root causes of anemia in these patients. Sepsis can cause "inflammatory anemia" and combine with iron deficiency anemia. Current anemia treatments include drugs that stimulate red blood cell production and intravenous iron supplements. Some think that iron supplements can worsen infections by feeding pathogens, but this is not conclusively proven. Since transfused red blood cells (RBC) also contain iron, small doses of intravenous iron might help sepsis patients with iron deficiency. There is a need for a study on the effects of epoetin alfa and iron derisomaltose on hemoglobin (Hb) levels in sepsis patients. Hypothesis and Aim Treating anemia in sepsis patients could increase Hb levels and reduce RBC transfusions, improving patient outcomes. This study aims to evaluate the effects of epoetin alfa ± iron derisomaltose on Hb levels and RBC transfusion rates. Primary Endpoints: 1\. Hb difference at study exit (discharge from ICU/death/bleeding/need for surgery/day 15 whatever comes first) and day 1 corrected for Hb increase due to possible RBC transfusion Secondary Endpoints: 1. Hb difference on days 8 and 1 corrected for Hb increase due to possible RBC transfusion 2. Hb difference on days 15 and 1 corrected for Hb increase due to possible RBC transfusion 3. number of blood transfusions 4. percentage of patients receiving at least one blood transfusion 5. actual vs. predicted mortality 6. prevalence of deep vein thrombosis and pulmonary embolism 7. mortality rates in ICU, hospital, 30-day, and 90-day. Materials and Methods: This will be a randomized controlled clinical trial recruting 200 patients Inclusion Criteria: 1. age ≥18 2. diagnosed sepsis (Sepsis-3 definition) or septic shock (Septic Shock-3 definition) 3. hemoglobin \<120 g/L for both sexes Exclusion Criteria: 1. bleeding 2. decompensated liver disease 3. inherited microcytic disorders 4. macrocytosis 5. contraindications to pharmacological prophylaxis for venous thromboembolism 6. pregnancy 7. allergy to epoetin alfa and/or iron derisomaltose. 8. ferritin \>800 ng/mL. 9. inability to take consent Study Group: 1. epoetin alfa 50 u/kg IV (days 1, 3, 5, 8, 10, 12) 2. iron derisomaltose 0.2g IV when RET-He \<29.3 pg (days 1, 3, 5, 8, 10, 12) 3. algorithm for red blood cell transfusions Control Group: 1\. algorithm for red blood cell transfusions Laboratory Parameters: Initial: interleukin-6, procalcitonin, C-reactive protein, creatinine, ammonia, blood urea nitrogen, aspartate aminotransferase, alanine aminotransferase, total bilirubin, complete blood count (CBC), reticulocytes (RET), ferritin, iron, transferrin. Serial: CBC and RET (days 1, 3, 5, 8, 10, 12)

Timeline

Start

2024-11-10

Primary completion

2026-12-31

Completion

2027-04-01

Publications

• Background Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R, Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS, Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-10. doi: 10.1001/jama.2016.0287.
• Background IRONMAN Investigators; Litton E, Baker S, Erber WN, Farmer S, Ferrier J, French C, Gummer J, Hawkins D, Higgins A, Hofmann A, De Keulenaer B, McMorrow J, Olynyk JK, Richards T, Towler S, Trengove R, Webb S; Australian and New Zealand Intensive Care Society Clinical Trials Group. Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial : A randomized trial of IV iron in critical illness. Intensive Care Med. 2016 Nov;42(11):1715-1722. doi: 10.1007/s00134-016-4465-6. Epub 2016 Sep 30.
• Background Czempik PF, Wilczek D, Herzyk J, Krzych LJ. Hospital-Acquired Anemia in Patients Hospitalized in the Intensive Care Unit: A Retrospective Cohort Study. J Clin Med. 2022 Jul 6;11(14):3939. doi: 10.3390/jcm11143939.
• Background Czempik PF, Pluta MP, Krzych LJ. Physiologic approach to red blood cell transfusion in non-bleeding critically ill patients. Arch Med Sci. 2022 Aug 30;18(5):1423-1425. doi: 10.5114/aoms/152217. eCollection 2022. No abstract available.
• Background Czempik PF, Wiorek A. Comparison of Standard and New Iron Status Biomarkers: A Prospective Cohort Study in Sepsis Patients. Healthcare (Basel). 2023 Mar 30;11(7):995. doi: 10.3390/healthcare11070995.
• Background Czempik PF, Wiorek A. Iron deficiency in sepsis patients managed with divided doses of iron dextran: a prospective cohort study. Sci Rep. 2023 Mar 31;13(1):5264. doi: 10.1038/s41598-023-32002-y.
• Background Czempik PF, Wiorek A. Iron deficiency in sepsis patients based on reticulocyte hemoglobin and hepcidin concentration: a prospective cohort study. Arch Med Sci. 2023 May 24;19(3):805-809. doi: 10.5114/aoms/161802. eCollection 2023.

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