Long-term safety and efficacy of ferric citrate in phosphate-lowering and iron-repletion effects among patients with on hemodialysis: A multicenter, open-label, Phase IV trial

Abstract

Background: We explored the long-term safety and efficacy of ferric citrate in hemodialysis patients in Taiwan, and further evaluated the iron repletion effect and change of iron parameters by different baseline groups.

Methods: This was a 12-month, Phase IV, multicenter, open-label study. The initial dose of ferric citrate was administered by patients' clinical condition and further adjusted to maintain serum phosphorus at 3.5-5.5 mg/dL. The primary endpoint was to assess the safety profiles of ferric citrate. The secondary endpoints were to evaluate the efficacy by the time-course changes and the number of subjects who achieved the target range of serum phosphorus.

Results: A total of 202 patients were enrolled. No apparent or unexpected safety concerns were observed. The most common treatment-emergent adverse events were gastrointestinal-related with discolored feces (41.6%). Serum phosphorus was well controlled, with a mean dose of 3.35±1.49 g/day, ranging from 1.5 to 6.0 g/day. Iron parameters were significantly improved. The change from baseline of ferritin and TSAT were 227.17 ng/mL and 7.53%, respectively (p-trend<0.001), and the increase started to slow down after 3-6 months of treatment. In addition, the increase trend was found only in patients with lower baseline level of ferritin (≤500 ng/mL) and TSAT (<30%).

Conclusions: Ferric citrate is an effective phosphate binder with favorable safety profile in ESRD patients. The iron-repletion by ferric citrate is effective, and the increase is limited in patients with a higher baseline. In addition to controlling hyperphosphatemia, ferric citrate also shows additional benefits in the treatment of renal anemia.

Clinical trial registration: ClinicalTrials.gov ID: NCT03256838; 12/04/2017.

Fig 1. Flow diagram of subjects by completion status.

Fig 2

The impact of ferric citrate treatment on the changes of (A) serum phosphorus, (B) hemoglobin and serum iron, (C) TSAT, ferritin, and TIBC and (D) iPTH and calcium from M0 to EOT. Abbreviations: TSAT, transferrin saturation; TIBC, total iron binding capacity; iPTH, intact parathyroid hormone; M0, baseline; EOT, end-of-treatment. The values were expressed as mean and standard error (SE).

Fig 3

Changes in (A) ferritin and (B) TSAT from M0 to EOT according to different baselines of ferritin (<300 ng/mL, 300–500 ng/mL, >500 ng/mL) and TSAT (<30%, ≥30%). The trend of continuous data was calculated by a linear regression. Abbreviations: TSAT, transferrin saturation; M0, baseline; EOT, end-of-treatment. The values were expressed as mean and standard error (SE).