Hepcidine and Iron Deficiency in Critically Ill Patients

Study Overview
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Brief Summary
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Anaemia is very frequent among critically ill patients, concerning more than 60 % of them at admission and more than 80% at intensive care unit discharge. Iron deficiency is also frequent at admission, with prevalence around 25 to 40%. During their stay in Intensive Care Unit, critically ill patients are exposed to repeated blood samples and to other blood losses (daily blood loss has been evaluated to be as high as 128 ml/day in median), this leads to direct iron loss. Prevalence of iron deficiency may thus be very important at Intensive Care Unit discharge. However, iron deficiency diagnosis is complicated in these patients, since inflammation induces an increase in plasma ferritin levels and a decrease in transferrin saturation, the two usual markers of iron deficiency. As a consequence, iron deficiency is usely under-diagnosed in these patients. Treatment of iron deficiency may be indicated to correct anaemia but also to improve patients fatigue and muscular weakness. The characterization of iron metabolism regulation by the hormone hepcidin opened new ways for the understanding and the follow-up of these complex clinical situations (combining inflammation and iron deficiency). Indeed, iron deficiency is associated with a decrease in hepcidin synthesis, while iron overload induces hepcidin synthesis. Furthermore, low hepcidin levels are required to mobilize iron from stores. Hepcidin has thus be proposed as a marker of iron deficiency in critically ill patients. To date, standard immunological methods of hepcidin quantitation are only proposed in the reasearch setting and could not be proposed in the clinical setting because it is too expensive. New approaches for hepcidin quantification, based on mass spectrometry are proposed and may be routinely implemented. We make the hypothesis that treating iron deficiency in critically ill anemic patients, diagnosed by hepcidin quantification, may improve the post-Intensive Care Unit rehabilitation, and may thus reduce post-Intensive Care Unit cost linked to hospital stay and anaemia treatment. The aim of this study is to evaluate the medical economic interest of a new diagnostic method for iron deficiency, based on a quantitative dosage of hepcidin by mass spectrometry in critically ill anaemic patients.

Official Title
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Medical Economic Analysis of the Interest of Hepcidin Quantitation by Quantitative Mass Spectrometry for the Diagnosis of Iron Deficiency in Anemic Critically Ill Patients

Conditions
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Anemia, Critical Illness, Hospitalized for 5 Days or More

Intervention / Treatment
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* Biological: hepcidin
* Biological: ferritin and transferrin saturation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized man/woman in reanimation unit for at least 5 days. Age ≥ 18 years old. Patient having an anaemia such as defined by the WHO (World Health Organization) (for man: Hemoglobin < 13 g/dl, for woman: Hemoglobin < 12 g/dl). Signed inform consent by the patient or a close person. Subject affiliated to a national health insurance Exclusion Criteria: Known iron metabolism pathology (such as primitive or secondary hemochromatosis, …). Chronic anaemia (Hemoglobin ≤ 10 g/dl for more than 3 months). Current chemotherapy. Patient having an organ transplant Expected survival < 28 days post Intensive Care Unit discharge. Pregnancy Patient deprived of freedom, by judicial or administrative order. Major protected by the law. Contra-indication to the injectable iron treatment (allergy to ferric carboxymaltose, infection derivates (bacteriamy < 48 hours) untreated). Non speaking French patient, or patient unable to answer a questionnaire because of any neurologic disorder (stroke, brain trauma….).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dosage of hepcidin<br>In order to assess iron deficiency, patients randomized in this arm will have dosage of hepcidin by mass spectrometry | Biological: hepcidin<br>* In order to assess iron deficiency by innovative method (dosage of Hepcidin), an additional collection of blood will be done at day 0 (and weekly until Intensive Care Unit discharge) and at Day 15 after Intensive Care Unit discharge. Treatement of Iron deficiency anaemia and anaemia of chronic disease using intravenous iron (± erythropoietin) will be encouraged (or not) according to hepcidin levels<br>|
| Active Comparator: Usual biomarker dosage<br>In order to assess iron deficiency, patients randomized in this arm will have usual biomarker dosages (ferritin and transferrin saturation) | Biological: ferritin and transferrin saturation<br>* In order to assess iron deficiency by using usual biomarkers (ferritin and transferrin saturation), collection of blood will be done at day 0 (and weekly until Intensive Care Unit discharge) and at Day 15 after Intensive Care Unit discharge. Treatement of Iron deficiency anaemia and anaemia of chronic disease using intravenous iron (± erythropoietin) will be encouraged (or not) according to ferritin levels.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hospital cost |  | from Intensive Care Unit discharge to 90 days after (D90) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lenght of hospital stay post-Intensive Care Unit |  | until day 90 after Intensive Care Unit discharge | 
| Haemoglobin levels |  | 15 days post-Intensive Care Unit discharge | 
| Iron deficiency prevalence |  | at Day 15 after Intensive Care Unit discharge | 
| Fatigue | Fatigue will be assessed by the MFI-20 questionnaire | 30 days after Intensive Care Unit discharge | 
| Proportion of patient alive |  | at Day 90 after Intensive Care Unit discharge | 
| Proportion of patient at home |  | at Day 90 after Intensive Care Unit discharge | 
| Comparison between mass spectrometry and immuno-detection methods for hepcidin quantification (ancillary study) |  | from inclusion to Day15 after Intensive Care Unit discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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iron deficiency, dosage of hepcidin, usual biomarker (ferritin and transferrin saturation), mass spectrometry, immuno-detection, anaemia in intensive care unit