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Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease.
PLoS One. 2017; 12(11):e0188712.Plos

Abstract

Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively. The starting dose in both trials was three 1-g (elemental iron 210 mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in the phase 2 and 3 trials to lower serum phosphate concentrations to a target range (0.97-1.13 mmol/L) and to achieve a ≥10-g/L hemoglobin increase, respectively. Safety was assessed in all patients who received ≥1 dose of FC (n = 190) and placebo (n = 188). Treatment-emergent adverse events (AEs) were reported in 143 of 190 (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients; gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%], respectively). Specific events reported in >5% of patients (FC vs. placebo, respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39 [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18 [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest serum phosphate decline, with few excursions below the normal range. When used for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at higher rates than placebo, while simultaneously correcting two of the principal metabolic manifestations of CKD (iron deficiency anemia and relative hyperphosphatemia).

Authors+Show Affiliations

Stanford University School of Medicine, Department of Medicine - Med/Nephrology, Stanford, California, United States of America.Denver Nephrology, Denver, Colorado, United States of America.Keryx Biopharmaceuticals, Inc., Boston, Massachusetts, United States of America.Renal Associates PA, San Antonio, Texas, United States of America.Keryx Biopharmaceuticals, Inc., Boston, Massachusetts, United States of America.Hofstra Northwell School of Medicine, Division of Medicine - Kidney Diseases and Hypertension, Great Neck, New York, United States of America.

Pub Type(s)

Clinical Trial, Phase II
Clinical Trial, Phase III
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

29186198

Citation

Chertow, Glenn M., et al. "Safety and Efficacy of Ferric Citrate in Patients With Nondialysis-dependent Chronic Kidney Disease." PloS One, vol. 12, no. 11, 2017, pp. e0188712.
Chertow GM, Block GA, Neylan JF, et al. Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease. PLoS One. 2017;12(11):e0188712.
Chertow, G. M., Block, G. A., Neylan, J. F., Pergola, P. E., Uhlig, K., & Fishbane, S. (2017). Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease. PloS One, 12(11), e0188712. https://doi.org/10.1371/journal.pone.0188712
Chertow GM, et al. Safety and Efficacy of Ferric Citrate in Patients With Nondialysis-dependent Chronic Kidney Disease. PLoS One. 2017;12(11):e0188712. PubMed PMID: 29186198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety and efficacy of ferric citrate in patients with nondialysis-dependent chronic kidney disease. AU - Chertow,Glenn M, AU - Block,Geoffrey A, AU - Neylan,John F, AU - Pergola,Pablo E, AU - Uhlig,Katrin, AU - Fishbane,Steven, Y1 - 2017/11/29/ PY - 2017/06/09/received PY - 2017/11/08/accepted PY - 2017/11/30/entrez PY - 2017/12/1/pubmed PY - 2018/1/2/medline SP - e0188712 EP - e0188712 JF - PloS one JO - PLoS One VL - 12 IS - 11 N2 - Two randomized, placebo-controlled trials conducted in patients with nondialysis-dependent (NDD) chronic kidney disease (CKD), iron deficiency anemia, and normal or elevated serum phosphorus demonstrated that ferric citrate (FC) significantly increased hemoglobin and decreased serum phosphate concentrations. Pooling these trial results could provide a more robust evaluation of the safety and efficacy of FC in this population. We pooled results of a phase 2 (n = 149) and 3 trial (n = 233) of patients randomized and treated for up to 12 and 16 weeks, respectively. The starting dose in both trials was three 1-g (elemental iron 210 mg) tablets/day with food, up to 12 tablets/day. Doses were titrated in the phase 2 and 3 trials to lower serum phosphate concentrations to a target range (0.97-1.13 mmol/L) and to achieve a ≥10-g/L hemoglobin increase, respectively. Safety was assessed in all patients who received ≥1 dose of FC (n = 190) and placebo (n = 188). Treatment-emergent adverse events (AEs) were reported in 143 of 190 (75.3%) FC-treated and 116 of 188 (61.7%) placebo-treated patients; gastrointestinal AEs were the most frequent (94 [49.5%] vs. 52 [27.7%], respectively). Specific events reported in >5% of patients (FC vs. placebo, respectively) included discolored feces (41 [21.6%] vs. 0 [0.0%]), diarrhea (39 [20.5%] vs. 23 [12.2%]), constipation (35 [18.4%] vs. 19 [10.1%]), and nausea (18 [9.5%] vs. 8 [4.3%]). Twenty FC-treated (10.5%) and 21 placebo-treated patients (11.2%) experienced a serious AE. Two patients (1.1%) died in each group. A pooled efficacy assessment demonstrated a consistent hemoglobin rise and modest serum phosphate decline, with few excursions below the normal range. When used for treatment of patients with NDD-CKD, FC contributes to gastrointestinal AEs at higher rates than placebo, while simultaneously correcting two of the principal metabolic manifestations of CKD (iron deficiency anemia and relative hyperphosphatemia). SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/29186198/Safety_and_efficacy_of_ferric_citrate_in_patients_with_nondialysis_dependent_chronic_kidney_disease_ L2 - https://dx.plos.org/10.1371/journal.pone.0188712 DB - PRIME DP - Unbound Medicine ER -