Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers and Critical Care Patients

Critical Illness Clinical Trial

— SOFI  

Official title:

Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers Versus Critical Care Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01443624
• Other study ID #: P101104
• Secondary ID: 2011-000819-10
• Status: Completed
• Phase: N/A
• First received: September 27, 2011
• Last updated: August 13, 2013
• Start date: October 2011
• Est. completion date: August 2013

Study information

• Verified date: August 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the inflammatory state of critically ill patients will reduce the oxydative stress induced by iron injections, compared to the one induced in healthy volunteers. It will be an open "proof-of-concept" study aimed at evaluating iron toxicity in critically ill patients (n=40) as compared to healthy volunteers (n=40).

The investigators will compare the oxidative stress (principal judgment criteria= 8-iso-PGF2α) following a 100 mg injection of iron (at T0, T2, T6 and T24 hours post injection) in both groups and the investigators will compare the effect of repeated injections in the critically ill patients.

Description:

Anemia is frequent among critically ill patients, with 60% of the patients being anemic at admission and more than 80% at discharge. This anemia is associated with an increased MORBI-mORTALITY. However, therapeutic options, mainly transfusion and erythropoietin, are disappointing. There is a remaining therapeutic option, iron injection, which has not been fully evaluated because of potential restrictions: inflammation may prevent its efficacy, and iron could be toxic, notably through the generation of oxidative stress. Our research is aimed at exploring the benefit of iron treatment in the critical care anemia.

The investigators already demonstrated in a MURIN model of critical care anemia that the master regulator of iron metabolism, hepcidin, is repressed and that iron can be mobilized from the stores despite inflammation. In addition, in an observational human study, the investigators reported that 25% of critically ill patients had iron deficiency and low to normal hepcidin levels.

All together, these data indicate that iron therapy may be beneficial in this situation. In the present study, the investigators evaluate the toxicity of iron in that context of critical care anemia. Iron, especially non-transferrin bound iron, is known to induce the generation of oxygen-derived free radicals through the Fenton reaction. However, the generation of oxidative stress secondary to iron injection has not been investigated in the critically ill. In our animal model, preliminary data indicate that the production of oxidative stress in the serum following iron injection may be prevented by inflammation.

Objectives: To evaluate the pro-oxidant toxicity of iron injections in critically ill patients and in healthy volunteers. The investigators hypothesize that the oxidative stress will be reduced in critically ill as compared to healthy volunteers

Human study : It will be an open "proof-of-concept" study aiming at evaluating iron toxicity in critically ill patients (n=40) as compared to healthy volunteers (n=40).

The investigators will compare the oxidative stress (principal judgment criteria= 8-iso-PGF2α) following a 100 mg injection of iron (at T0, T2, T6 and T24 hours post injection) in both groups and the investigators will compare the effect of repeated injections in the critically ill patients.

Perspectives:

This study should confirm that iron does not produce more oxidant stress in critically ill patients than in healthy volunteers. The animal study should help to precise the efficacy of this treatment, in addition to its toxicity. All these results will help to design a phase III randomized study of intravenous iron in critically ill anemic patients

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

INCLUSION CRITERIA:

• Man or woman hospitalized in critical care unit,

• between 18 and 90 years old

• clinical examination completed

• written consent from the patient or a patient's relative depending on the awareness of the patient

• an iron injection has been prescribed by the responsible physician to the patient

• anemia defined as hemoglobin level =11 g/dl

• iron deficiency define by at least one of the following criteria :

• ferritin < 100 µg/l

• ferritin between 100 and 300 µg/l with transferrin saturation < 20%,

• soluble transferrin receptor (RsTf) =1,4 mg/l,

• ratio RsTf/log(ferritin) =0,7,

• blood loss = 1 blood weight.

EXCLUSION CRITERIA:

• do not subscribe to the french health insurance program

• Pregnancy or nursing

• past medical history of iron overload or disfunction in iron metabolism (= primary or secondary hemochromatosis)

• Recent bacteremia defined as positive in the 48 hours preceding the injection. Having a non positive hemoculture is not an exclusion criteria

• Suspicion of a novel current infection defined by a new fever with temperature over >38°5 for at least three times during the last 48hours. A persisting fever for more than 48 hours without argument for a new infection is not an exclusion criteria.

• known allergia to the iron- hydroxide complex or one of the excipient

• active chronic alcoholism

• oral iron treatment during the last 24 hours. Usage of antioxidant (vitamin C, vitamin E) within the 24 hours preceding the iron injection.

• person participating to another clinical trial or being in the exclusion phase of a clinical trial

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Critical Illness

Intervention

Drug:
• critical care patients venofer
100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment

Locations

Country	Name	City	State
France	CHU Bichat-Claude Bernard	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum 8-iso-PGF2a	oxidative stress	0 hours	No
Primary	serum 8-iso-PGF2a	oxidative stress	2 hours	No
Primary	serum 8-iso-PGF2a	oxidative stress	6 hours	No
Primary	serum 8-iso-PGF2a	oxidative stress	24 hours	No
Secondary	Advanced Oxidized Protein Product	oxidative stress	0 hours	No
Secondary	Advanced Oxidized Protein Product	oxidative stress	2 hours	No
Secondary	Advanced Oxidized Protein Product	oxidative stress	6 hours	No
Secondary	Advanced Oxidized Protein Product	oxidative stress	24 hours	No