Hepcidine and Iron Deficiency in Critically Ill Patients

NCT ID: NCT02276690

Last Updated: 2017-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 408 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2017-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Dosage of hepcidin

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

Group Type: EXPERIMENTAL

hepcidin

Intervention Type: 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

Usual biomarker dosage

In order to assess iron deficiency, patients randomized in this arm will have usual biomarker dosages (ferritin and transferrin saturation)

Group Type: ACTIVE_COMPARATOR

ferritin and transferrin saturation

Intervention Type: 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.

Interventions

hepcidin

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

Intervention Type: BIOLOGICAL

ferritin and transferrin saturation

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Hospitalized man/woman in reanimation unit for at least 5 days.

2. Age ≥ 18 years old.

3. 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).

4. Signed inform consent by the patient or a close person.

5. Subject affiliated to a national health insurance

Exclusion Criteria

1. Known iron metabolism pathology (such as primitive or secondary hemochromatosis, …).

2. Chronic anaemia (Hemoglobin ≤ 10 g/dl for more than 3 months).

3. Current chemotherapy.

4. Patient having an organ transplant

5. Expected survival < 28 days post Intensive Care Unit discharge.

6. Pregnancy

7. Patient deprived of freedom, by judicial or administrative order.

8. Major protected by the law.

9. Contra-indication to the injectable iron treatment (allergy to ferric carboxymaltose, infection derivates (bacteriamy < 48 hours) untreated).

10. Non speaking French patient, or patient unable to answer a questionnaire because of any neurologic disorder (stroke, brain trauma….).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Montpellier

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sigismond SL LASOCKI, PU-PH

Role: STUDY_DIRECTOR

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

Sylvain SL LEHMANN, PU-PH

Role: STUDY_CHAIR

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

Locations

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

Angers, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 28919067 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33588893 (View on PubMed)

Other Identifiers

9190

Identifier Type: -

Identifier Source: org_study_id