Clinical Efficacy and Safety of Intravenous Ferric Carboxymaltose for Treatment of Restless Legs Syndrome: A Multicenter, Randomized, Placebo-controlled Clinical Trial

Abstract

Study objectives: Iron therapy is associated with improvements in restless legs syndrome (RLS). This multicenter, randomized, double-blind study evaluated the effect of intravenous ferric carboxymaltose (FCM) on RLS.

Methods: A total of 209 adult patients with a baseline International Restless Legs Syndrome (IRLS) score ≥15 were randomized (1:1) to FCM (750 mg/15 mL) or placebo on study Days 0 and 5. Ongoing RLS medication was tapered starting on Day 5, with the goal of discontinuing treatment or achieving the lowest effective dose. Co-primary efficacy endpoints were change from baseline in IRLS total score and the proportion of patients rated as much/very much improved on the Clinical Global Impression-investigator (CGI-I) scale at Day 42 in the "As-Treated" population.

Results: The "As-Treated" population comprised 107 FCM and 101 placebo recipients; 88 (82.2%) and 68 (67.3%), respectively, completed the Day 42 assessment. The IRLS score reduction was significantly greater with FCM versus placebo: least-squares mean (95% confidence interval [CI]) -8.0 (-9.5, -6.4) versus -4.8 (-6.4, -3.1); P = 0.0036. No significant difference was observed in the proportion of FCM (35.5%) and placebo (28.7%) recipients with a CGI-I response (odds ratio 1.37 [95% CI: 0.76, 2.47]; P = 0.2987). Fewer patients treated with FCM (32.7%) than placebo (59.4%) received RLS interventions between Day 5 and study end (P = 0.0002). FCM was well tolerated.

Conclusion: The IRLS score improved with intravenous FCM versus placebo, although the combination of both co-primary endpoints was not met. Potential methodological problems in the study design are discussed.

Keywords: Restless legs syndrome; Restless legs syndrome – clinical assessment; Restless legs syndrome – neurobiology; ferric carboxymaltose; iron repletion.