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)

Conditions

• Anemia
• Sepsis
• Septic Shock

Interventions

DRUG

Iron

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

DRUG

EPO

Epoetin alfa 50 units/kg IV 3 times weekly

DRUG

0.9 % NaCl

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

Sponsors & Collaborators

• Piotr Czempik

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-11-10

Primary Completion

2026-12-31

Completion

2027-04-01

Countries

• Poland

Study Locations