Evaluation of Oxidative Stress Induced by Iron Injection in Healthy Volunteers and Critical Care Patients
- Conditions
- Critical Illness
- Interventions
- Drug: critical care patients venofer
- Registration Number
- NCT01443624
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description critical care patients venofer critical care patients venofer Critically ill patients are injected with Venofer (ferric hydroxide sucrose) 100mg IV in one hour (in critically ill patients the injection could be repeated on day 2 (200mg) and 4 (100mg) depending on treatment
- Primary Outcome Measures
Name Time Method serum 8-iso-PGF2α 24 hours oxidative stress
- Secondary Outcome Measures
Name Time Method Advanced Oxidized Protein Product 24 hours oxidative stress
Trial Locations
- Locations (1)
CHU Bichat-Claude Bernard
🇫🇷Paris, France