A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

Ferumoxytol for the treatment of iron deficiency and iron-deficiency anemia of pregnancy.

INTRODUCTION: A litany of recent evidence supports the morbidity of intra-natal iron-deficiency anemia and its prodrome, iron deficiency. Oral iron administered during second and third trimesters does not get to the developing fetus if the mother is iron deficient. This is especially concerning as the rapidly developing fetal brain is in particular need of iron sufficiency. Intra-natal iron deficiency is associated with autism, schizophrenia and abnormal brain structure. The obstetrical literature reports an unacceptably high incidence of gastrointestinal adverse events with oral iron. The time iron honored standard in the United States for intravenous iron replenishment in gravidas is iron sucrose. While safe and effective, four to seven visits are required to accomplish what newer formulations can achieve with one. METHODS: Ferumoxytol is a superparamagnetic iron oxide linked to polyglucose sorbitol carboxymethylether-binding elemental iron tightly allowing administration of complete replacement doses in 15-30 min. Herein, we report the results of 131 consecutive, non-selected, iron-deficient second- and third-trimester pregnant women who received either 510 mg of intravenous (IV) ferumoxytol twice or 1020 mg once. RESULTS: Hemoglobin and iron parameter increments were highly statistically significant. No adverse events were reported. We report how a single infusion is safe and effective as the same dose over two visits, saving an unnecessary visit and IV placement, while reducing cost. CONCLUSION: Ferumoxytol represents an efficacious and safe method of administration of IV iron which improves convenience for patients and practitioners, and is cost saving due to fewer visits. PLAIN LANGUAGE SUMMARY: One or two infusions of intravenous iron for iron deficiency or iron-deficiency anemia of pregnancy simplifies careThis study was conducted to highlight the inconvenience of multiple doses of IV iron and how administering the same dose in one or two infusions simplifies care. We report how a single infusion is as safe and effective as the same dose over two visits, saving an unnecessary visit and IV placement, while reducing cost. This study supports a growing body of evidence, to date, unreported, with ferumoxytol in pregnancy, reporting improved convenience and decreased costs with higher doses of IV iron in one or two visits.