Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies

Yang, Xinglong; Yang, Baiyuan; Mao, Ming; Li, Shimei; Wang, Fang; Zhu, Zhigang; Ji, Chang Lok; Long, Juan; Hu, Fayun; Xu, Zhenhe; Ren, Hui; Liu, Bin

doi:10.1016/j.sleep.2019.01.040

Cited by 12 publications

(6 citation statements)

References 27 publications

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“…The studies of IV therapy, with one exception, set inclusion criteria for ferritin at <300 μg/L, a range not therapeutically achievable with oral iron. A meta‐analysis of studies of IV iron therapy in idiopathic RLS suggested that IV iron is effective and tolerable for patients with RLS irrespective of peripheral iron status or formulation used 3,21 …”

Section: Discussionmentioning

confidence: 99%

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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

Short,

Allen,

Earley

et al. 2024

American J Hematol

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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.

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Section: Discussionmentioning

confidence: 99%

“…3,21 T A B L E 2 Outcomes at Week 6.Note: For patients missing IRLSS scores at Week 6, the baseline IRLSS score was carried forward and used in the analysis. For all other outcomes, no data imputation methods were used.…”

mentioning

confidence: 99%

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

Short,

Allen,

Earley

et al. 2024

American J Hematol

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“…Pharmacological treatment: Iron substitution is the first component of treatment [88,92,93]. Symptomatic drug treatment includes dopaminergic medication (levodopa, dopamine agonists), α2δ ligands (gabapentin, pregabalin), and opioids and GABA-A receptor agonists.…”

Section: Sleep-related Movement Disordersmentioning

confidence: 99%

Pharmacological Treatments of Sleep–Wake Disorders: Update 2023

Kallweit,

Kallweit

2023

CTN

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Biological, environmental, behavioral, and social factors can influence sleep and lead to sleep disorders or diseases. Sleep disorders are common, numerous, and heterogeneous in terms of their etiology, pathogenesis, and symptomatology. The management of sleep–wake circadian disorders (SWCDs) includes education on sleep hygiene, behavioral strategies, psychotherapy (cognitive behavioral therapy (CBT), particularly), instrument-based treatments (i.e., positive airway pressure therapy, hypoglossal nerve stimulation), and pharmacotherapy. Depending on the disease, therapy varies and is executed sequentially or can be a combination of several forms of therapy. Drugs used for SWCDs include traditional sleep- or wake-promoting agents and chronotherapeutic agents. Recently, novel medications, which more precisely act on specific neurochemical systems (i.e., the orexin system) important for sleep and waking, are also increasingly being used. In this review, the pharmacotherapy of common sleep disorders (insomnia, sleep-related breathing disorder, central disorders of hypersomnolence, circadian rhythm sleep–wake disorders, parasomnias, and sleep-related movement disorders) embedded in the overall therapeutic concept of each disorder is presented. There is also an outlook on possible future pharmacotherapies.

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“…Oral iron supplements are known to change the gut microbiome in favour of pathogenic bacteria, which are iron dependent, 72 and it has been suggested that intravenous iron supplementation also affects the gut microbiome 73 and metabolome. 74 Furthermore, since ID has been linked to restless legs syndrome 75 76 and ID correction has been shown to alleviate restless legs symptoms, [77][78][79] intravenous iron might reduce these complaints in KTRs. 80 The EFFECT-KTx trial addresses the effects of iron treatment using an intravenous solution.…”

Section: Strengths and Limitations Of This Studymentioning

confidence: 99%

Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

Vinke

Eisenga²,

Sanders³

et al. 2023

BMJ Open

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IntroductionIron deficiency (ID) is common and has been associated with an excess mortality risk in kidney transplant recipients (KTRs). In patients with chronic heart failure and ID, intravenous iron improves exercise capacity and quality of life. Whether these beneficial effects also occur in KTRs is unknown. The main objective of this trial is to address whether intravenous iron improves exercise tolerance in iron-deficient KTRs.Methods and analysisThe Effect of Ferric Carboxymaltose on Exercise Capacity after Kidney Transplantation study is a multicentre, double-blind, randomised, placebo-controlled clinical trial that will include 158 iron-deficient KTRs. ID is defined as plasma ferritin <100 µg/L or plasma ferritin 100–299 µg/L with transferrin saturation <20%. Patients are randomised to receive 10 mL of ferric carboxymaltose (50 mg Fe3+/mL, intravenously) or placebo (0.9% sodium chloride solution) every 6 weeks, four dosages in total. The primary endpoint is change in exercise capacity, as quantified by the 6 min walk test, between the first study visit and the end of follow-up, 24 weeks later. Secondary endpoints include changes in haemoglobin levels and iron status, quality of life, systolic and diastolic heart function, skeletal muscle strength, bone and mineral parameters, neurocognitive function and safety endpoints. Tertiary (explorative) outcomes are changes in gut microbiota and lymphocyte proliferation and function.Ethics and disseminationThe protocol of this study has been approved by the medical ethical committee of the University Medical Centre Groningen (METc 2018/482;) and is being conducted in accordance with the principles of the Declaration of Helsinki, the Standard Protocol Items: Recommendations for Interventional Trials checklist and the Good Clinical Practice guidelines provided by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use. Study results will be disseminated through publications in peer-reviewed journals and conference presentations.Trial registration numberNCT03769441.

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Efficacy and tolerability of intravenous iron for patients with restless legs syndrome: evidence from randomized trials and observational studies

Cited by 12 publications

References 27 publications

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

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

Pharmacological Treatments of Sleep–Wake Disorders: Update 2023

Effect of Intravenous Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx): rationale and study protocol for a double-blind, randomised, placebo-controlled trial

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