Hepcidine and Iron Deficiency in Critically Ill Patients (HEPCIDANE)

• ClinicalTrials.gov Identifier: NCT02276690
• Recruitment Status: Completed
• First Posted: October 28, 2014
• Last Update Posted: October 6, 2017
• Sponsor: University Hospital, Montpellier
• Information provided by (Responsible Party): University Hospital, Montpellier

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Anemia; Critical Illness; Hospitalized for 5 Days or More	Biological: hepcidin; Biological: ferritin and transferrin saturation	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Diagnostic
• Official Title: Medical Economic Analysis of the Interest of Hepcidin Quantitation by Quantitative Mass Spectrometry for the Diagnosis of Iron Deficiency in Anemic Critically Ill Patients
• Actual Study Start Date: August 2014
• Actual Primary Completion Date: October 26, 2016
• Actual Study Completion Date: September 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dosage of hepcidin; In order to assess iron deficiency, patients randomized in this arm will have dosage of hepcidin by mass spectrometry	Biological: 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
Active Comparator: Usual biomarker dosage; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Hospital cost [ Time Frame: from Intensive Care Unit discharge to 90 days after (D90) ]

Secondary Outcome Measures :

1. Lenght of hospital stay post-Intensive Care Unit [ Time Frame: until day 90 after Intensive Care Unit discharge ]
2. Haemoglobin levels [ Time Frame: 15 days post-Intensive Care Unit discharge ]
3. Iron deficiency prevalence [ Time Frame: at Day 15 after Intensive Care Unit discharge ]
4. Fatigue [ Time Frame: 30 days after Intensive Care Unit discharge ]
   Fatigue will be assessed by the MFI-20 questionnaire
5. Proportion of patient alive [ Time Frame: at Day 90 after Intensive Care Unit discharge ]
6. Proportion of patient at home [ Time Frame: at Day 90 after Intensive Care Unit discharge ]
7. Comparison between mass spectrometry and immuno-detection methods for hepcidin quantification (ancillary study) [ Time Frame: from inclusion to Day15 after Intensive Care Unit discharge ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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….).

Contacts and Locations

Locations

France

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

Angers, France, 49000

Sponsors and Collaborators

University Hospital, Montpellier

Investigators

• Study Director: Sigismond SL LASOCKI, PU-PH; Department of Anesthesiology & Critical Care, Angers University Hospital, France
• Study Chair: Sylvain SL LEHMANN, PU-PH; Biochemistry and clinical proteomic laboratory, IRMB, St Eloi University Hospital

More Information

Publications:

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.

• Responsible Party: University Hospital, Montpellier
• ClinicalTrials.gov Identifier: NCT02276690
• Other Study ID Numbers: 9190
• First Posted: October 28, 2014
• Last Update Posted: October 6, 2017
• Last Verified: November 2015

Keywords provided by University Hospital, Montpellier:

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

Additional relevant MeSH terms:

Anemia, Iron-Deficiency; Critical Illness; Anemia; Hematologic Diseases; Disease Attributes; Pathologic Processes; Anemia, Hypochromic; Iron Metabolism Disorders; Metabolic Diseases; Hepcidins; Anti-Infective Agents