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

Published:January 31, 2013DOI:https://doi.org/10.1053/j.ajkd.2012.11.041

      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.

      Index Words

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