Efficacy of pramipexole in restless legs syndrome: A six‐week, multicenter, randomized, double‐blind study (effect‐RLS study)

Abstract

We evaluated the efficacy of pramipexole versus placebo in restless legs syndrome (RLS) for 6 weeks. Overall, 345 patients were randomly assigned in a 1:2 ratio to receive either placebo (n = 115) or pramipexole (n = 230) with a starting dose of 0.125 mg/day. The dose was individually optimized according to the Patient Global Impression (PGI) assessment, up to a maximum of 0.75 mg/day. The primary endpoint consisted of two assessments: the change from baseline in the International RLS Study Group Rating Scale (IRLS) and the proportion of patients with Clinical Global Impressions-Improvement (CGI-I) assessments of "much/very much improved" (CGI-I responders) at week 6. Secondary endpoints included PGI and IRLS responder rates. Patient demographics and baseline characteristics were comparable between treatment groups. At baseline, mean IRLS scores were 24.9 (placebo) and 24.7 (pramipexole), representing severely affected patients. After 6 weeks, adjusted mean reductions (+/-SE) in IRLS score were 5.7 (+/-0.9) for placebo (median dose 0.47 mg/day) and 12.3 (+/-0.6) for pramipexole (median dose 0.35 mg/day; P < 0.0001). CGI-I responder rates were 32.5% (placebo) and 62.9% (pramipexole) (P < 0.0001). For all secondary endpoints, pramipexole showed superior results. Pramipexole was well tolerated throughout the study.

Practice guideline summary: Treatment of restless legs syndrome in adults

“…Pramipexole. It is highly likely that pramipexole improves RLS symptoms as measured by the IRLS (3 Class I 16-18 and 6 Class II studies [19][20][21][22][23][24] over varying timeframes). It is likely that pramipexole improves PLMS (3 Class II studies 20,22,25 ) and subjective sleep measures (1 Class I 17 and 3 Class II studies, 19,21,23 with an additional Class II study lacking the precision to exclude an important effect 24 ).…”

Sleep improvement for restless legs syndrome patients. Part IV: meta-analysis comparison of effect sizes of vibratory stimulation sham pads and placebo pills

“…Details of the placebo analysis of 12 RLS drug trials [17][18][19][20][21][22][23][24][25][26][27][28] and the two VS trials 4,29 have been previously published. Controls for the drug trials were pharmacologically inert pills identical in appearance to study drugs.…”

Effect of Nonergot Dopamine Agonists on Symptoms of Restless Legs Syndrome

“…[17][18][19][20][21][22][23][24][25][26][27][28][29][30] We excluded 30 trials from analysis, including those that had an open-label design, 31-33 a cross-over design, [34][35][36][37][38] or were withdrawal studies (meaning that the effect of continuing treatment vs withdrawing treatment after a doubleblind treatment period was assessed). 39,40 In the included trials, patients received ropinirole in 7 trials (n = 1,698 subjects), 17,[19][20][21][28][29][30] pramipexole in 4 trials (n = 825 subjects), [22][23][24]27 rotigotine in 2 trials (n = 404 subjects), 18,26 and sumanirole in 1 trial (n = 270 subjects). 25 Thirteen trials provided CGI-I scale responder rates, [17][18][19][20][21][22][23][24][25][26][27][28]...…”