Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With CKD and Iron Deficiency

Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With Moderate to Severe Chronic Kidney Disease (CKD) With Iron Deficiency

The main objective of the study is to compare the impact of oral ferric citrate compared to standard of care oral ferrous sulfate on serum iron, percent transferrin saturation, ferritin, hepcidin and hemoglobin levels in individuals with moderate to severe chronic kidney disease (CKD) and absolute iron deficiency.

Study Overview

• Status: Completed
• Conditions: Anemia; Chronic Kidney Disease; Iron Deficiency
• Intervention / Treatment: Drug: ferric citrate; Drug: ferrous sulfate

Detailed Description

Ferric citrate is an FDA-approved oral phosphorus binder that has been shown to be effective in reducing serum phosphorus and fibroblast growth factor 23 (FGF23) concentrations and increasing iron stores and hemoglobin in individuals with non-dialysis-dependent CKD who have iron-deficiency anemia. This may prove to be advantageous in individuals with pre-dialysis CKD who require iron supplementation for iron-deficiency anemia. This is because ferric citrate may not only restore iron stores in individuals who are iron deficient, but by lowering FGF23 concentrations, ferric citrate may increase local and systemic concentrations of 1,25-dihydroxyvitamin D, a powerful inhibitor of hepcidin synthesis, potentially attenuating the increase in hepcidin following oral iron supplementation. When compared to standard iron supplementation therapies (e.g., oral ferrous sulfate) that powerfully stimulate hepcidin secretion, this may then allow for greater iron bioavailability by increasing iron absorption in the gut while also reducing the degree of iron sequestration in reticuloendothelial system stores. However, little is known about the comparative effectiveness of treatment with oral ferric citrate vs. oral ferrous sulfate (currently the standard of care) in increasing iron stores and hemoglobin in iron-deficient CKD patients. If ferric citrate is shown to not only improve overall iron status, but also partially mitigate the long-term effects of iron supplementation on hepcidin secretion by increasing endogenously produced 1,25-dihydroxyvitamin D, this may indicate that ferric citrate can provide superior short- and long-term effects on iron-restricted erythropoiesis in CKD as compared to the current standard of care. The main objectives of the study are to compare the impact of ferric citrate compared to standard of care ferrous sulfate on serum iron, percent transferrin saturation (TSAT), ferritin, hemoglobin and hepcidin concentrations in individuals with moderate to severe CKD and absolute iron deficiency.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or greater
• Moderate to severe CKD not requiring dialysis (eGFR 15 - 45 ml/min/1.73 m2 by CKD-EPI)
• Absolute iron deficiency (serum ferritin <300ng/ml and Transferrin Saturation < 30%)

Exclusion Criteria:

• Hemoglobin concentrations > 13 g/dL
• Known disorder of iron homeostasis (e.g., hemochromatosis)
• Known gastrointestinal disorder (irritable bowel disease, inflammatory bowel disease)
• Known liver disease (ALT/AST or bilirubin > 3x normal)
• Serum phosphorus concentrations < 3.0 mg/dL
• Any known cause of anemia other than iron deficiency or CKD (e.g., sickle cell anemia)
• Symptomatic gastrointestinal bleeding within 12 weeks prior to the screening visit.
• Subjects receiving any form of renal replacement therapy including hemodialysis, peritoneal dialysis, or renal transplant.
• Pregnancy or lactation in female participants
• Severe anemia defined as a hemoglobin < 8.0 g/dL for males or a hemoglobin <7.0 g/dL for females.
• Receipt of erythropoiesis stimulating agents within 4 weeks of screening.
• Receipt of intravenous iron therapy within 8 weeks of screening.
• Blood transfusion within 4 weeks of screening
• Known allergies or severe adverse reactions to previous oral iron therapy
• Current use of oral phosphorus binders.
• Current use of an active vitamin D analog

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ferric citrate; Participants randomized to the ferric citrate arm will receive 2 grams of ferric citrate three times a day with each meal.	Drug: ferric citrate; Participants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals.; Other Names: Auryxia
Active Comparator: ferrous sulfate; Participants randomized to the ferrous sulfate arm will receive 325 mg of ferrous sulfate three times a day	Drug: ferrous sulfate; Participants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Ferritin From Baseline to End of Treatment	The change in serum ferritin concentrations from the baseline of the study to the 12 week time point.	Baseline and 12 weeks
Change in Transferrin Saturation From Baseline to End of Treatment	The change in serum transferrin saturation from the baseline to the end of treatment	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hemoglobin From Baseline to End of Treatment	The change in hemoglobin concentrations from the baseline visit to the 12-week time point.	Baseline and 12 weeks
Change in Hepcidin From Baseline to the End of Treatment	The change in hepcidin concentrations from the baseline visit to the 12-week time point.	Baseline and 12 weeks
Change in Fibroblast Growth Factor 23 From Baseline to the End of Treatment	The change in fibroblast growth factor 23 concentrations from the baseline visit to the 12-week time point.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of Alabama at Birmingham
• Investigators: Principal Investigator: Orlando M Gutierrez, MD, University of Alabama at Birmingham

Publications and helpful links

General Publications

• Womack R, Berru F, Panwar B, Gutierrez OM. Effect of Ferric Citrate versus Ferrous Sulfate on Iron and Phosphate Parameters in Patients with Iron Deficiency and CKD: A Randomized Trial. Clin J Am Soc Nephrol. 2020 Sep 7;15(9):1251-1258. doi: 10.2215/CJN.15291219. Epub 2020 Jul 21.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): February 12, 2019
• Study Completion (Actual): March 30, 2019

Study Registration Dates

• First Submitted: August 30, 2016
• First Submitted That Met QC Criteria: August 30, 2016
• First Posted (Estimate): September 2, 2016

Study Record Updates

• Last Update Posted (Actual): March 24, 2020
• Last Update Submitted That Met QC Criteria: March 20, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Urologic Diseases; Hematologic Diseases; Renal Insufficiency; Anemia, Hypochromic; Anemia; Iron Metabolism Disorders; Kidney Diseases; Renal Insufficiency, Chronic; Anemia, Iron-Deficiency
• Other Study ID Numbers: F160318006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

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