A Pilot Randomized Trial of Ferric Citrate Coordination Complex for the Treatment of Advanced CKD

Abstract

Background: Researchers have yet to determine the optimal care of patients with advanced CKD. Evidence suggests that anemia and CKD-related disordered mineral metabolism (including abnormalities in phosphate and fibroblast growth factor 23 [FGF23]) contribute to adverse outcomes in this population.

Methods: To investigate whether fixed-dose ferric citrate coordination complex favorably affects multiple biochemical parameters in patients with advanced CKD, we randomly assigned 203 patients with eGFR≤20 ml/min per 1.73 m² 2:1 to receive a fixed dose of ferric citrate coordination complex (two tablets per meal, 210 mg ferric iron per tablet) or usual care for 9 months or until 3 months after starting dialysis. No single biochemical end point was designated as primary; sample size was determined empirically.

Results: The two groups had generally similar baseline characteristics, although diabetes and peripheral vascular disease were more common in the usual-care group. Ferric citrate coordination complex significantly increased hemoglobin, transferrin saturation, and serum ferritin, and it significantly reduced serum phosphate and intact FGF23 (P<0.001 for all). Of the 133 patients randomized to ferric citrate coordination complex, 31 (23%) initiated dialysis during the study period, as did 32 of 66 (48%) patients randomized to usual care (P=0.001). Compared with usual care, ferric citrate coordination complex treatment resulted in significantly fewer annualized hospital admissions, fewer days in hospital, and a lower incidence of the composite end point of death, provision of dialysis, or transplantation (P=0.002).

Conclusions: The beneficial effects of fixed-dose ferric citrate coordination complex on biochemical parameters, as well as the exploratory results regarding the composite end point and hospitalization, suggest that fixed-dose ferric citrate coordination complex has an excellent safety profile in an unselected population with advanced CKD and merits further study.

Keywords: CKD; FGF23; RCT; anemia; ferric citrate; hyperphosphatemia.

Figure 1.

Patient disposition. Two-hundred twenty patients were screened, 203 patients randomized (17 screen failures). All analyses were conducted using MITT population (patients who attended at least one postbaseline follow-up visit). Patients could be pre-emptively transplanted before dialysis or receive transplant after initiating dialysis. HD, hemodialysis; ITT, intent to treat; PD, peritoneal dialysis.

Figure 2.

Change in Anemia-related P parameters. Mean values of hemoglobin (A), transferrin saturation (B), and median serum ferritin (C). Statistical inference testing using mixed-effects model with repeated measures, *P<0.001 for between-group differences. BL, baseline.

Figure 3.

Change in bone and mineral related parameters. Mean values of serum P (A), median intact FGF23 (B), median intact PTH (C), and mean 1,25 dihydroxy vitamin D (D). Statistical inference testing using mixed-effects model with repeated measures, *P<0.001 for between-group differences. BL, baseline.

Figure 4.

Kaplan–Meier survival function curve for time to first hospitalization (A) and time to the composite end point of death, dialysis, or transplant in all patients (B).