Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients: A short-term randomized trial.

Author Department

Medicine

Document Type

Article, Peer-reviewed

Publication Date

5-2013

Abstract

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.

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