Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers and Critical Care Patients
Condition: Critical Illness
MeSH terms: Critical Illness
Study type: Interventional

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.
    

Detailed 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
    

Intervention name(s): critical care patients venofer
Intervention type(s): Drug
Intervention description(s): 100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment
Other intervention name(s): iron (ferric hydroxide sucrose) injection
Intervention MeSH terms: Ferric Oxide, Saccharated
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: iron; critical illness; oxidative stress