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.


METHODS
Prospective, phase 3, multicenter, open-label, randomized clinical trial.


METHODS
151 participants with hyperphosphatemia on maintenance hemodialysis therapy.


METHODS
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).


RESULTS
Primary outcome is dose-response of ferric citrate on serum phosphorus level; secondary outcomes are safety and tolerability.


METHODS
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.


CONCLUSIONS
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.
Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Jamie P
JP
Dwyer
Mohammed
M
Sika
Gerald
G
Schulman
Ingrid J
IJ
Chang
Michael
M
Anger
Mark
M
Smith
Mark
M
Kaplan
Steven
S
Zeig
Mark J
MJ
Koury
Samuel S
SS
Blumenthal
Julia B
JB
Lewis
D000284:Administration, Oral; D004305:Dose-Response Relationship, Drug; D005260:Female; D005290:Ferric Compounds / Q000008:administration & dosage*; D005500:Follow-Up Studies; D006397:Hematinics / Q000008:administration & dosage; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010758:Phosphorus / Q000097:blood; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects*; D013997:Time Factors; D016896:Treatment Outcome
D005290:Ferric Compounds; D006397:Hematinics; D010758:Phosphorus; C025314:ferric citrate