Acute Effects of Intravenous Iron on Oxidative Stress and Endothelial Dysfunction in Non-dialysis CKD

Study Overview
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Brief Summary
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The purpose of this study is to investigate the effects of acute intravenous iron administration on the endothelial function in non-dialysis Chronic Kidney Disease stages G3-G5 patients with anemia and iron deficiency, in relation to changes in oxidative and nitrosative status.

Official Title
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The Effects of a Single Intravenous Iron Upon Vascular Endothelium and Some Parameters of Oxidative Stress in Patients With Non-dialysis Chronic Kidney Disease

Conditions
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Renal Anemia, Iron Toxicity, Oxidative Stress, Endothelial Dysfunction

Intervention / Treatment
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* Drug: Sodium Chloride 0.9% Intravenous Solution
* Drug: Ferinject


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic kidney disease stages G3-G5 (defined according to KDIGO criteria); Anemia (defined according to KDIGO criteria) and iron deficiency defined as serum ferritin < 100 ng/mL and/or TSAT < 20% (KDIGO). Exclusion Criteria: contraindications of intravenous iron therapy: iron allergy, active infection, hemochromatosis, iron overload (serum ferritin > 500 ng/mL and/or transferrin saturation > 50%); treatment with iron and erythropoiesis-stimulating agents (at the time of recruitment and 6 months previously); active smoker status; antioxidant food supplements treatment in the last 3 months; clinically manifest bleeding; another cause of anemia (hemoglobinopathies, vitamin B12 and/or folic acid deficiency suggested by the megaloblastic peripheral blood smears's appearance, multiple myeloma and other paraproteinemias); severe anemia (Hb < 7 g/dl); baseline FMD < 7% (the existence of atherosclerosis which limits arterial reactivity); cancer (currently or in the past 6 months); hepatopathies (increased serum transaminases ≥ 3 x normal value) or hepatic impairment ≥ grade Child B; autoimmune disorders or significant inflammation (as defined by C-reactive protein > 5 mg/L); pregnancy or lactation; participation in other clinical trials over the upast 3 months; patient unwillingness.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Intervention: 250 mL Sodium Chloride 0.9% Intravenous Solution, representing control infusion, over 30 minutes. | Drug: Sodium Chloride 0.9% Intravenous Solution<br>* Physiologic saline infusion will be infused in day 1.<br>* Other names: Physiologic saline;Drug: Ferinject<br>* Ferric carboxymaltose will be infused in day 2.<br>* Other names: Ferric carboxymaltose;|
| Active Comparator: Ferric carboxymaltose<br>Intervention: 1000 mg Ferinject in 250 mL 0.9%NaCl, representing medication in study infusion, over 30 minutes. | Drug: Sodium Chloride 0.9% Intravenous Solution<br>* Physiologic saline infusion will be infused in day 1.<br>* Other names: Physiologic saline;Drug: Ferinject<br>* Ferric carboxymaltose will be infused in day 2.<br>* Other names: Ferric carboxymaltose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on endothelial function | Description of the endothelial function variation (changing in flow-mediated vasodilatation (FMD) endothelium-dependent, and also in serum sICAM-1, sVCAM-1 and nitric oxide metabolism parameters ) after administration of a single intravenous dose of iron versus a control solution, in CKD non-dialysis patients. | through study completion, an average of 1 year | 
| Oxidative stress | Description of some free radicals production's markers (lipid peroxidation and carbonyl stress assessment) and in antioxidant system in plasma markers variation after administration of a single intravenous iron dose versus a control solution, in non-dialysis CKD subjects. | through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between endothelial dysfunction and oxidative stress markers | Evaluation of correlations between changes in oxidative stress parameters and endothelial function after a single intravenous iron administration compared to a control solution in non-dialysis CKD subjects. | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CKD, anemia, iron, endothelial dysfunction, oxidative stress