Clinical trial NCT02888171: Impact of Ferric Citrate vs Ferrous Sulfate on Iron Parameters and Hemoglobin in Individuals With CKD and Iron Deficiency
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Kidney Disease
Iron Deficiency
Anemia
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
First posted: 2016-09-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in Ferritin From Baseline to End of Treatment
timeFrame: Baseline and 12 weeks
measure: Change in Transferrin Saturation From Baseline to End of Treatment
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in Hemoglobin From Baseline to End of Treatment
timeFrame: Baseline and 12 weeks
measure: Change in Hepcidin From Baseline to the End of Treatment
timeFrame: Baseline and 12 weeks
measure: Change in Fibroblast Growth Factor 23 From Baseline to the End of Treatment
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Orlando M Gutierrez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.