Dose-Response and Efficacy of Ferric Citrate to Treat Hyperphosphatemia in Hemodialysis Patients: A Short-term Randomized Trial

Background: Most dialysis patients require phosphate binders to control hyperphosphatemia. Ferric citrate has been tested in phase 2 trials as a phosphate binder. This trial was designed as a dose-response and efficacy trial. Study Design: Prospective, phase 3, multicenter, open-label, randomized clinical trial. Setting & Participants: 151 participants with hyperphosphatemia on maintenance hemodialysis therapy. Intervention: Fixed dose of ferric citrate taken orally as a phosphate binder for up to 28 days (1, 6, or 8 g/d in 51, 52, and 48 participants, respectively). Outcomes: Primary outcome is dose-response of ferric citrate on serum phosphorus level; secondary outcomes are safety and tolerability. Measurements: Serum chemistry tests including phosphorus, safety data. Results: 151 participants received at least one dose of ferric citrate. Mean baseline phosphorus levels were 7.3 +/- 1.7 (SD) mg/dL in the 1-g/d group, 7.6 +/- 1.7 mg/dL in the 6-g/d group, and 7.5 +/- 1.6 mg/dL in the 8-g/d group. Phosphorus levels decreased in a dose-dependent manner (mean change at end of treatment, -0.1 +/- 1.3 mg/dL in the 1-g/d group, -1.9 +/- 1.7 mg/dL in the 6-g/d group, and -2.1 +/- 2.0 mg/dL in the 8-g/d group). The mean difference in reduction in phosphorus levels between the 6- and 1-g/d groups was 1.3 mg/dL (95% CI, 0.69 to 1.9; P < 0.001), between the 8- and 1-g/d groups was 1.5 mg/dL (95% CI, 0.86 to 2.1; P < 0.001), and between the 8- and 6-g/d groups was 0.21 mg/dL (95% CI, -0.39 to 0.81; P = 0.5). The most common adverse event was stool discoloration. Limitations: Sample size and duration confirm efficacy, but limit our ability to confirm safety. Conclusions: Ferric citrate is efficacious as a phosphate binder in a dose-dependent manner. A phase 3 trial is ongoing to confirm safety and efficacy. Am J Kidney Dis. 61(5): 759-766. (C) 2013 by the National Kidney Foundation, Inc.