Abstract
BACKGROUND: Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. METHODS: Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin. RESULTS: In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 µg/L versus -69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups. CONCLUSIONS: FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.