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

NCT ID: NCT02888171

Last Updated: 2020-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2019-03-30

Brief Summary

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.

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.

Conditions

Chronic Kidney Disease; Iron Deficiency; Anemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ferric citrate

Participants randomized to the ferric citrate arm will receive 2 grams of ferric citrate three times a day with each meal.

Group Type: EXPERIMENTAL

ferric citrate

Intervention Type: DRUG

Participants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals.

ferrous sulfate

Participants randomized to the ferrous sulfate arm will receive 325 mg of ferrous sulfate three times a day

Group Type: ACTIVE_COMPARATOR

ferrous sulfate

Intervention Type: DRUG

Participants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day.

Interventions

ferric citrate

Participants randomized to the ferric citrate arm will take 2 grams of ferric citrate three times a day with meals.

Intervention Type: DRUG

ferrous sulfate

Participants randomized to the ferrous sulfate arm will take 325 mg of ferrous sulfate three times a day.

Intervention Type: DRUG

Other Intervention Names

Auryxia

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Orlando M. Gutierrez, MD, MMSc

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Orlando M Gutierrez, MD

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32694162 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

F160318006

Identifier Type: -

Identifier Source: org_study_id