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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Endothelial Dysfunction; Oxidative Stress; Renal Anemia; Iron Toxicity
• Intervention / Treatment: Drug: Sodium Chloride 0.9% Intravenous Solution; Drug: Ferinject

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Romania
  • Bucharest, Romania
    • "Dr. Carol Davila" Teaching Hospital of Nephrology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Intervention: 250 mL Sodium Chloride 0.9% Intravenous Solution, representing control infusion, over 30 minutes.	Drug: Sodium Chloride 0.9% Intravenous Solution; Physiologic saline infusion will be infused in day 1.; Other Names: Physiologic saline; Drug: Ferinject; Ferric carboxymaltose will be infused in day 2.; Other Names: Ferric carboxymaltose
Active Comparator: Ferric carboxymaltose; 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; Physiologic saline infusion will be infused in day 1.; Other Names: Physiologic saline; Drug: Ferinject; Ferric carboxymaltose will be infused in day 2.; Other Names: Ferric carboxymaltose

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Carol Davila University of Medicine and Pharmacy
• Collaborators: S.C. Sanador S.R.L
• Investigators: Study Chair: Gabriel Mircescu, Professor, Carol Davila University of Medicine and Pharmacy; Study Director: Cristina Capusa, Assoc. Prof., Carol Davila University of Medicine and Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): December 30, 2020
• Study Completion (Anticipated): December 20, 2022

Study Registration Dates

• First Submitted: December 18, 2017
• First Submitted That Met QC Criteria: December 24, 2017
• First Posted (Actual): January 3, 2018

Study Record Updates

• Last Update Posted (Actual): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 14, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: CKD, anemia, iron, endothelial dysfunction, oxidative stress
• Additional Relevant MeSH Terms: Hematologic Diseases; Anemia
• Other Study ID Numbers: 10488/19.04.2016

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No