Rotigotine in Hemodialysis-Associated Restless Legs Syndrome : A Randomized Controlled Trial

Background: Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease. Study Design: Double-blind placebo-controlled study. Setting & Participants: Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] >= 15) and Periodic Limb Movement Index (PLMI) >= 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe. Intervention: Following randomization and titration ( Outcomes & Measurements: Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score. Results: 30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7 +/- 0.4 for rotigotine and 1.3 +/- 0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P = 0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P = 0.05] and -0.81 [95% CI, -1.94 to 0.33; P = 0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (>= 50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (>= 2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0). Limitations: Small sample size and short duration. Conclusions: Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients. (C) 2016 by the National Kidney Foundation, Inc.Peer reviewe

Transdermal rotigotine for the perioperative management of restless legs syndrome

Abstract Background Immobilisation, blood loss, sleep deficiency, and (concomitant) medications during perioperative periods might lead to acute exacerbation of symptoms in patients with the restless legs syndrome (RLS). Continuous transdermal delivery of the dopamine agonist rotigotine provides stable plasma levels over 24 h and may provide RLS patients with a feasible treatment option for perioperative situations. To assess the feasibility of use of rotigotine transdermal patch for the perioperative management of moderate to severe RLS, long-term data of an open-label extension of a rotigotine dose-finding study were retrospectively reviewed. Methods The data of all 295 patients who had entered the 5-year study were screened independently by two reviewers for the occurrence of surgical interventions during the study period. The following data were included in this post-hoc analysis: patient age, sex, surgical intervention and outcome, duration of hospital stay, rotigotine maintenance dose at the time of surgery, rotigotine dose adjustment, and continuation/discontinuation of rotigotine treatment. All parameters were analysed descriptively. No pre-specified efficacy assessments (e.g. IRLS scores) were available for the perioperative period. Results During the study period, 61 surgical interventions were reported for 52 patients (median age, 63 years; 67% female); the majority of patients (85%) had one surgical intervention. The mean rotigotine maintenance dose at time of surgery was 3.1 ± 1.1 mg/24 h. For most interventions (95%), rotigotine dosing regimens were maintained during the perioperative period. Administration was temporarily suspended in one patient and permanently discontinued in another two. The majority (96%) of the patients undergoing surgery remained in the study following the perioperative period and 30 of these patients (61%) completed the 5-year study. Conclusions Although the data were obtained from a study which was not designed to assess rotigotine use in the perioperative setting, this post-hoc analysis suggests that treatment with rotigotine transdermal patch can be maintained during the perioperative period in the majority of patients and may allow for uninterrupted alleviation of RLS symptoms. Trial Registration The 5-year rotigotine extension study is registered with ClinicalTrials.gov, identifier NCT00498186.</p

Treatment of moderate to severe restless legs syndrome: 2-year safety and efficacy of rotigotine transdermal patch

<p>Abstract</p> <p>Background</p> <p>Rotigotine is a unique dopamine agonist with activity across D1 through D5 receptors as well as select adrenergic and serotonergic sites. This study reports the 2-year follow-up safety and efficacy data of an ongoing open-label multicenter extension study (NCT00498186) of transdermal rotigotine in patients with moderate to severe restless legs syndrome (RLS).</p> <p>Methods</p> <p>Patients received a once-daily patch application of an individually optimized dose of rotigotine between 0.5 mg/24 h to 4 mg/24 h. Safety assessments included adverse events (AEs) and efficacy was measured by the International RLS Study Group Severity Rating Scale (IRLS), RLS-6 scales and Clinical Global Impression (CGI). Quality of life (QoL) was measured by QoL-RLS.</p> <p>Results</p> <p>Of 310 patients who completed a 6-week placebo-controlled trial (SP709), 295 (mean age 58 ± 10 years, 66% females) were included in the open-label trial SP710. 64.7% (190/295 patients) completed the 2-year follow-up; 29 patients discontinued during the second year. Mean daily rotigotine dose after 2 years was 2.93 ± 1.14 mg/24 h with a 2.9% dose increase from year 1. Rotigotine was generally well tolerated. The rate of typical dopaminergic side effects, nausea and fatigue, was low (0.9% and 2.3%, respectively) during the second year; application site reactions were frequent but lower than in year 1 (16.4% vs. 34.5%). The IRLS total score improved from baseline of SP709 (27.8 ± 5.9) by 17.2 ± 9.2 in year 2 completers. Similar improvements were observed in RLS-6 scales, CGI scores and QoL-RLS. The responder rate in the CGI change item 2 ("much" and "very much" improved) was 95% after year 2.</p> <p>Conclusions</p> <p>Transdermal rotigotine is an efficacious and well-tolerated long-term treatment option for patients with moderate to severe RLS with a high retention rate during 2 years of therapy.</p> <p>Trial registration</p> <p>NCT00498186</p

Efficacy of rotigotine for treatment of moderate-to-severe restless legs syndrome:a randomised, double-blind, placebo-controlled trial

The air-sea gas transfer velocity k is frequently estimated as an empirical function of wind speed. However, it is widely recognized that k depends on processes other than wind speed alone. The small-eddy model, which describes periodic events of small eddies disturbing the sea surface with water from below, suggests a direct relation between k and the dissipation rate of turbulent kinetic energy E at the air-sea interface. This relation has been proven both in laboratories and in the field in various freshwater and coastal environments, but to date has not been verified in open ocean conditions. Here, concurrent North Atlantic field observations of E and eddy covariance measurements of DMS and CO2 air-sea gas flux are presented. Using E measurements, we compare the small-eddy model at various depths to previously published observations. Extrapolating the measured E profiles to the thickness of the viscous sublayer allows us to formulate a function of k that depends solely on the water side friction velocity uw, which can be inferred from direct eddy covariance measurements of the air-side friction velocity ua. These field observations are generally consistent with the theoretical small-eddy model. Utilizing a variable Schmidt number exponent in the model, rather than a constant value of 1/2 yields improved agreement between model and observations