Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study

Abstract

Background: Hyperphosphatemia in CKD patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. Trial design: This is an open-label active-drug-controlled multicenter randomized study. Methods: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio receiving either ferric citrate or sevelamer carbonate respectively for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated at every two weeks. Frequency and severity of adverse events were recorded. Results: 217 (90.4%) patients completed the study, with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59±0.54mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (P>0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group were significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) in the sevelamer carbonate group experienced drug-related TEAEs, most were mild and tolerable. Common drug-related TEAEs were "gastrointestinal disorders", including diarrhea (12.9% vs. 2.5%), feacal discoloration (14.7% vs. 0%), and constipation (1.7% vs. 7.4%) in ferric citrate and sevelamer carbonate group respectively. Conclusion: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.