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

NCT06670963 | Recruiting Phase 4

• 1 other identifier: BNW-1-006/N/4/K
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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. 1.Hb difference on days 8 and 1 corrected for Hb increase due to possible RBC transfusion
2. 2.Hb difference on days 15 and 1 corrected for Hb increase due to possible RBC transfusion
3. 3.number of blood transfusions
4. 4.percentage of patients receiving at least one blood transfusion
5. 5.actual vs. predicted mortality
6. 6.prevalence of deep vein thrombosis and pulmonary embolism
7. 7.mortality rates in ICU, hospital, 30-day, and 90-day.
8. 8.age ≥18
9. 9.diagnosed sepsis (Sepsis-3 definition) or septic shock (Septic Shock-3 definition)
10. 10.hemoglobin \<120 g/L for both sexes
11. 11.bleeding
12. 12.decompensated liver disease
13. 13.inherited microcytic disorders
14. 14.macrocytosis
15. 15.contraindications to pharmacological prophylaxis for venous thromboembolism
16. 16.pregnancy
17. 17.allergy to epoetin alfa and/or iron derisomaltose.
18. 18.ferritin \>800 ng/mL.
19. 19.inability to take consent
20. 20.epoetin alfa 50 u/kg IV (days 1, 3, 5, 8, 10, 12)
21. 21.iron derisomaltose 0.2g IV when RET-He \<29.3 pg (days 1, 3, 5, 8, 10, 12)
22. 22.algorithm for red blood cell transfusions

Conditions

Anemia; Sepsis; Septic Shock

Keywords

anemia; sepsis; septic shock; epoetin alfa; iron derisomaltose; red blood cell; hemoglobin; intensive care unit

Outcome Measures

Primary Outcomes (1)

• Hemoglobin concentration difference at exit from the study

  The difference between hemoglobin concentration at exit from the study and day 1 corrected for Hb increase due to possible RBC transfusion \[RBC volume x RBC Hb concentration/study subject's blood volume (weight x 65 mL for women/weight x 75 mL for men)\]

  From enrollment to day 15/death/discharge from ICU/bleeding episode/surgery whatever comes first

Secondary Outcomes (12)

• Hemoglobin concentration difference at 1 week

  From enrollment to day 8 (if a study subject still in the trial)

• Hemoglobin concentration difference at 2 weeks

  From enrollment to day 15 (if a study subject still in the trial)

• Number of red blood cell units transfused

  From enrollment to day 15/death/discharge from ICU/bleeding episode/surgery whatever comes first

• Tranfusion rate

  From enrollment to day 15/death/discharge from ICU/bleeding episode/surgery whatever comes first

• Deep vein thrombosis prevalence

  From enrollment to day 15/death/discharge from ICU/bleeding episode/surgery whatever comes first

Study Arms (2)

Epoetin alfa +/- ferric derisomaltose

EXPERIMENTAL

Epoetin alfa 50 units/kg IV 3 times weekly and ferric derisomaltose 0.2g IV if reticulocyte hemoglobin equivalent \<29.3 pg

Drug: Iron; Drug: EPO

Placebo

PLACEBO COMPARATOR

0.9% NaCl

Drug: 0.9 % NaCl

Interventions

Iron DRUG

Iron derisomaltose 0.2g IV if reticulocyte hemoglobin equivalent \<29.3 pg (lower limit for the local laboratory reference range for reticulocyte hemoglobin equivalent)

Epoetin alfa +/- ferric derisomaltose

EPO DRUG

Epoetin alfa 50 units/kg IV 3 times weekly

Epoetin alfa +/- ferric derisomaltose

0.9 % NaCl DRUG

Volume of 0.9% NaCl identical as volume of medications used in experimental arm

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age ≥18,
• diagnosed sepsis (Sepsis-3) or septic shock (Septic Shock-3),
• hemoglobin \<120 g/L in both sexes.

You may not qualify if:

• bleeding,
• decompensated liver disease,
• inherited microcytic disorders,
• macrocytosis,
• contraindications to pharmacological prophylaxis of VTE,
• pregnancy,
• allergy to epoetin alfa and/or iron derisomaltose,
• ferritin concentration \>800 ng/mL,
• unable to take informed consent.

Sponsors & Collaborators

• Piotr Czempik: lead

Study Sites (1)

Uniwersyteckie Centrum Kliniczne im. prof. K. Gibińskiego Śląskiego Uniwersytetu Medycznego w Katowicach

Katowice, 40-752, Poland

RECRUITING

Related Publications (7)

• 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.

  PMID: 26903338 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.

  PMID: 27686346 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.

  PMID: 35887702 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.

  PMID: 36160360 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.

  PMID: 37046922 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.

  PMID: 37002279 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.

  PMID: 37313179 BACKGROUND

MeSH Terms

Conditions

Anemia; Sepsis; Shock, Septic

Interventions

Iron; Sodium Chloride

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Transition Elements; Metals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Sodium Compounds

Central Study Contacts

Piotr F. Czempik, MD, PhD

CONTACT

00487894201; pczempik@sum.edu.pl

Agnieszka Wiórek, MD, PhD

CONTACT

00487894201; agnieszka.wiorek@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor, MD, PhD

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 1, 2024
• Study Start: November 10, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)