A randomized, double-blind, placebo-controlled trial of intravenous iron sucrose in restless legs syndrome

Abstract

Objective: The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS. Methods:The study was a randomized, parallel-group double-blind study of 1000 mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra.Results: At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned breakpoint given the lack of both adequate power and any indication for clinically significant benefit.Conclusions: High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies.

Brazilian consensus on guidelines for diagnosis and treatment for restless legs syndrome

“…The systematic review allowed the identification of two studies using the primary route iron 84,85 and four primary studies that used intravenous iron 86,87,88,89 . The use of iron led to a reduction of 3.8 points in RLS Severity Scale, and dopaminergic agonists reduce an average of 5.7 points.…”

“…Finally, it must be emphasized the efficacy of opioids, particularly methadone, not only treating the symptoms of RLS as well as reducing the symptoms of augmentation and restoring sleep 86,109 .…”

Treatment of Restless Legs Syndrome

“…Other forms of parenteral iron, including ferric carboxymaltose appear to be safe and effective [36]. A controlled study of iron sucrose did not show benefit [37]. Parenteral iron replacement avoids the adverse effects of oral replacement, and may be effective for months following treatment.…”

Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial

“…Compromised iron status is an important disorder, possibly contributing to the cause of RLS 3. However, the causal relationship still remains unclear, and there is much debate about how to adequately assess iron status in RLS patients 4, 5, 6, 7, 8. The potential relationship between low iron status and RLS has led to increased interest in the use of iron replacement therapy to treat this disorder 1.…”

“…Study results have varied, most likely because of the different iron formulations and dosages used, as well as study design. Although some previous studies excluded anemic patients,7 all studies to date have included patients of varied iron status, but have not provided clear evidence about which RLS patients might benefit most from iron treatment 6, 7, 8, 9, 10, 11…”