The Use of Epoetin Alfa and Iron Derisomaltose in the Treatment of Anemia in Patients With Sepsis or Septic Shock Hospitalized in the Intensive Care Unit: a Randomized Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Hemoglobin concentration difference at exit from the study
研究概览
简要总结
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:
- 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:
- Hb difference on days 8 and 1 corrected for Hb increase due to possible RBC transfusion
- Hb difference on days 15 and 1 corrected for Hb increase due to possible RBC transfusion
- number of blood transfusions
- percentage of patients receiving at least one blood transfusion
- actual vs. predicted mortality
- prevalence of deep vein thrombosis and pulmonary embolism
- 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:
- age ≥18
- diagnosed sepsis (Sepsis-3 definition) or septic shock (Septic Shock-3 definition)
- hemoglobin <120 g/L for both sexes
Exclusion Criteria:
- bleeding
- decompensated liver disease
- inherited microcytic disorders
- macrocytosis
- contraindications to pharmacological prophylaxis for venous thromboembolism
- pregnancy
- allergy to epoetin alfa and/or iron derisomaltose.
- ferritin >800 ng/mL.
- inability to take consent
Study Group:
- epoetin alfa 50 u/kg IV (days 1, 3, 5, 8, 10, 12)
- iron derisomaltose 0.2g IV when RET-He <29.3 pg (days 1, 3, 5, 8, 10, 12)
- algorithm for red blood cell transfusions
Control Group:
- 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)
详细描述
Project Description:
Project Title: The use of epoetin alfa and iron derisomaltose in treating anemia in patients with sepsis or septic shock in the ICU: a randomized controlled clinical trial.
Project Acronym: EpoAid
Theoretical Background and Rationale: Up to 66% of patients have anemia at admission to the intensive care unit. Additionally, many patients develop anemia during hospitalization in the intensive care unit due to illness and iatrogenic blood loss for laboratory diagnostics. After 72 hours 95% of intensive care unit patients are anemic. Anemia increases the risk of tissue oxygen deficiency, which is particularly important in sepsis or septic shock patients who may have peripheral perfusion disorders due to infection. Anemia should be treated causally because red blood cell transfusions can lead to adverse effects, including immunomodulation leading to innate immunity suppression, which is particularly significant in critically ill sepsis or septic shock patients. Anemia caused by sepsis is known as inflammatory anemia (AI). Sepsis patients often have mixed anemia, combining features of AI and iron deficiency anemia (IDA) - AI+IDA. Currently available treatments for mixed anemia include erythropoiesis-stimulating agents (ESA) and intravenous iron supplements (e.g., iron derisomaltose). Manufacturers of intravenous iron products contraindicate their use in infections since intravenous iron could theoretically exacerbate infections by stimulating pathogen growth. However, there is no conclusive data on this. Considering that stored red blood cells are also a source of iron that pathogens can use, it seems that fractional doses of intravenous iron could benefit sepsis patients with diagnosed iron deficiency. Additionally, ESA administration could cause functional iron deficiency, where small doses of intravenous iron might also be beneficial.
Attempts to use ESA and intravenous iron in the general ICU population have yielded inconclusive results due to methodological errors. In the IRONMAN study comparing iron carboxymaltose with placebo, no difference in transfusion rates (primary endpoint) was found, but higher Hb levels were observed at hospital discharge in the intervention group (107 vs. 100 g/L). This trial had some methodological flaws: intravenous iron was administered regardless of anemia etiology, red blood cell transfusion decisions were made by clinicians - there was no transfusion algorithm, and the average hospital stay was 11 days - maximal effect of intravenous iron is seen after 3-4 weeks, at least 2 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Epoetin alfa +/- ferric derisomaltose
Epoetin alfa 50 units/kg IV 3 times weekly and ferric derisomaltose 0.2g IV if reticulocyte hemoglobin equivalent <29.3 pg
干预措施: Iron (Drug)
Epoetin alfa +/- ferric derisomaltose
Epoetin alfa 50 units/kg IV 3 times weekly and ferric derisomaltose 0.2g IV if reticulocyte hemoglobin equivalent <29.3 pg
干预措施: EPO (Drug)
Placebo
0.9% NaCl
干预措施: 0.9 % NaCl (Drug)
结局指标
主要结局
Hemoglobin concentration difference at exit from the study
时间窗: From enrollment to day 15/death/discharge from ICU/bleeding episode/surgery whatever comes first
The difference between hemoglobin concentration at exit from the study and day 1 corrected for Hb increase due to possible RBC transfusion \[RBC volume x RBC Hb concentration/study subject's blood volume (weight x 65 mL for women/weight x 75 mL for men)\]
次要结局
- 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)
- Pulmonaly embolism prevalence(From enrollment to day 15/death/discharge from ICU/bleeding episode/surgery whatever comes first)
- Intensive care unit mortality(From enrollment to discharge from ICU)
- 30-day mortality(From enrollment to day 30)
- 90-day mortality(From enrollment to day 90)
- Actual vs. predicted intensive care unit mortality(From enrollment to discharge from ICU)
研究者
Piotr Czempik
Assistant Professor, MD, PhD
Medical University of Silesia