Hepcidine and Iron Deficiency in Critically Ill Patients

NCT02276690 | Completed

• 1 other identifier: 9190
• Study Type: interventional
• Target: 408
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anemia; Critical Illness; Hospitalized for 5 Days or More

Keywords

iron deficiency; dosage of hepcidin; usual biomarker (ferritin and transferrin saturation); mass spectrometry; immuno-detection; anaemia in intensive care unit

Outcome Measures

Primary Outcomes (1)

• Hospital cost

  from Intensive Care Unit discharge to 90 days after (D90)

Secondary Outcomes (7)

• 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

  30 days after Intensive Care Unit discharge

• Proportion of patient alive

  at Day 90 after Intensive Care Unit discharge

Study Arms (2)

Dosage of hepcidin

EXPERIMENTAL

In order to assess iron deficiency, patients randomized in this arm will have dosage of hepcidin by mass spectrometry

Biological: hepcidin

Usual biomarker dosage

ACTIVE COMPARATOR

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

Interventions

hepcidin BIOLOGICAL

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

Dosage of hepcidin

ferritin and transferrin saturation BIOLOGICAL

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.

Usual biomarker dosage

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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….).

Sponsors & Collaborators

• University Hospital, Montpellier: lead

Study Sites (1)

Department of Anesthesiology & Critical Care, Angers University Hospital, 4 rue larrey

Angers, 49000, France

Location

Related Publications (2)

• Lasocki S, Puy H, Mercier G, Lehmann S; Hepcidane study group. Impact of iron deficiency diagnosis using hepcidin mass spectrometry dosage methods on hospital stay and costs after a prolonged ICU stay: Study protocol for a multicentre, randomised, single-blinded medico-economic trial. Anaesth Crit Care Pain Med. 2017 Dec;36(6):391-396. doi: 10.1016/j.accpm.2017.04.009. Epub 2017 Sep 14.

  PMID: 28919067 BACKGROUND

• Lasocki S, Asfar P, Jaber S, Ferrandiere M, Kerforne T, Asehnoune K, Montravers P, Seguin P, Peoc'h K, Gergaud S, Nagot N, Lefebvre T, Lehmann S; Hepcidane study group. Impact of treating iron deficiency, diagnosed according to hepcidin quantification, on outcomes after a prolonged ICU stay compared to standard care: a multicenter, randomized, single-blinded trial. Crit Care. 2021 Feb 15;25(1):62. doi: 10.1186/s13054-020-03430-3.

  PMID: 33588893 DERIVED

MeSH Terms

Conditions

Anemia; Critical Illness; Iron Deficiencies

Interventions

Hepcidins; Ferritins

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Iron-Regulatory Proteins; Proteins; Amino Acids, Peptides, and Proteins; Antimicrobial Cationic Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Iron-Binding Proteins; Carrier Proteins; Metalloproteins

Study Officials

• Sigismond SL LASOCKI, PU-PH

  Department of Anesthesiology & Critical Care, Angers University Hospital, France

  STUDY DIRECTOR

• Sylvain SL LEHMANN, PU-PH

  Biochemistry and clinical proteomic laboratory, IRMB, St Eloi University Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2014
• First Posted: October 28, 2014
• Study Start: August 1, 2014
• Primary Completion: October 26, 2016
• Study Completion: September 1, 2017
• Last Updated: October 6, 2017

Record last verified: 2015-11

Locations

FR (1)