Oral Ferric Maltol for the Treatment of Iron-Deficiency Anemia in Patients With CKD: A Randomized Trial and Open-Label Extension.

RATIONALE & OBJECTIVE Iron-deficiency anemia is common in patients with chronic kidney disease (CKD) not requiring kidney replacement therapy (KRT). We evaluated effects of oral iron replacement therapy with ferric maltol in these patients. STUDY DESIGN Phase 3, double-blind, randomized, placebo-controlled trial (AEGIS-CKD) and open-label extension. SETTING & PARTICIPANTS Adults with stage 3 or 4 CKD and iron-deficiency anemia at 30 US centers. INTERVENTION Oral ferric maltol at 30mg or placebo twice daily for 16 weeks (2:1 randomization) followed by ferric maltol at 30mg twice daily for up to 36 weeks (all patients). OUTCOME Change from baseline in hemoglobin (primary end point at week 16), ferritin, transferrin saturation, and serum iron; safety. RESULTS 167 patients were randomized (ferric maltol, n=111; placebo, n=56). At week 16, hemoglobin had increased significantly with ferric maltol versus placebo (least-squares mean difference: 0.5±0.2 [SE] g/dL; 95% CI, 0.1-0.9; P=0.01). Ferritin, transferrin saturation, and serum iron increased with ferric maltol but declined with placebo (all P<0.05). Hemoglobin levels were sustained up to week 52 in patients continuing ferric maltol and increased in patients switching from placebo to ferric maltol. The most frequent adverse events were gastrointestinal (randomized phase: 41% vs 30% [ferric maltol vs placebo]; open-label phase: 56% vs 46%, respectively). Adverse events led to treatment withdrawal in 7 patients (6%) receiving ferric maltol and 5 patients (9%) receiving placebo during double-blind treatment, and 11 patients (9%) during the open-label extension. LIMITATIONS Heterogeneity in baseline ferritin levels; high proportion of female participants; single-arm open-label extension. CONCLUSIONS Ferric maltol was associated with statistically significant (week 16) and sustained (up to week 52) increases in hemoglobin and iron indices in patients with CKD and iron deficiency, and was well tolerated during treatment for up to 52 weeks. FUNDING Funded by Shield Therapeutics (UK) Ltd. TRIAL REGISTRATION Registered at ClinicalTrials.gov with study number NCT02968368.