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

Phase 4

• Conditions: Oxidative Stress; Renal Anemia; Endothelial Dysfunction; Iron Toxicity
• Interventions: Drug: Sodium Chloride 0.9% Intravenous Solution; Drug: Ferinject

• Registration Number: NCT03388385
• Lead Sponsor: Carol Davila University of Medicine and Pharmacy

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-09-20
• Study First Submitted: 2017-12-18
• Study First Submitted QC: 2017-12-24
• Study First Posted: 2018-01-03
• Primary Completion: 2020-12-30
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-14
• Last Update Posted: 2022-08-16
• Study Completion: 2022-12-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Sodium Chloride 0.9% Intravenous Solution	Intervention: 250 mL Sodium Chloride 0.9% Intravenous Solution, representing control infusion, over 30 minutes.
Placebo	Ferinject	Intervention: 250 mL Sodium Chloride 0.9% Intravenous Solution, representing control infusion, over 30 minutes.
Ferric carboxymaltose	Sodium Chloride 0.9% Intravenous Solution	Intervention: 1000 mg Ferinject in 250 mL 0.9%NaCl, representing medication in study infusion, over 30 minutes.
Ferric carboxymaltose	Ferinject	Intervention: 1000 mg Ferinject in 250 mL 0.9%NaCl, representing medication in study infusion, over 30 minutes.

Primary Outcome Measures

Name	Time	Method
Effect on endothelial function	through study completion, an average of 1 year	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.
Oxidative stress	through study completion, an average of 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Correlation between endothelial dysfunction and oxidative stress markers	through study completion, an average of 1 year	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.

Trial Locations

Locations (1)

"Dr. Carol Davila" Teaching Hospital of Nephrology; 🇷🇴 Bucharest, Romania