Annaelle Zietz, Josefin E Kaufmann, Karin Wiesner, Sandro Kevin Fischer, Martina Wiegert, Wilma Dj Verhagen-Kamerbeek, Yannik Rottenberger, Anne Schwarz, Nils Peters, Henrik Gensicke, Friedrich Medlin, Jens Carsten Möller, Bartosz Bujan, Leo H Bonati, Marcel Arnold, Sabine Schaedelin, René M Müri, Lars G Hemkens, Patrik Michel, Philippe A Lyrer, Jeremia P Held, Gary A Ford, Andreas R Luft, Christopher Traenka, Stefan T Engelter
{"title":"Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial.","authors":"Annaelle Zietz, Josefin E Kaufmann, Karin Wiesner, Sandro Kevin Fischer, Martina Wiegert, Wilma Dj Verhagen-Kamerbeek, Yannik Rottenberger, Anne Schwarz, Nils Peters, Henrik Gensicke, Friedrich Medlin, Jens Carsten Möller, Bartosz Bujan, Leo H Bonati, Marcel Arnold, Sabine Schaedelin, René M Müri, Lars G Hemkens, Patrik Michel, Philippe A Lyrer, Jeremia P Held, Gary A Ford, Andreas R Luft, Christopher Traenka, Stefan T Engelter","doi":"10.1177/23969873241255867","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery.</p><p><strong>Aim and hypothesis: </strong>To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo.</p><p><strong>Design: </strong>ESTREL (<u>E</u>nhancement of <u>S</u>troke <u>RE</u>habilitation with <u>Levodopa</u>) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial.</p><p><strong>Participants: </strong>610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living.</p><p><strong>Intervention: </strong>Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset.</p><p><strong>Comparison: </strong>Matching placebo plus standardized rehabilitation.</p><p><strong>Outcomes: </strong>The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events.</p><p><strong>Conclusion: </strong>The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.</p>","PeriodicalId":46821,"journal":{"name":"European Stroke Journal","volume":null,"pages":null},"PeriodicalIF":5.8000,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Stroke Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/23969873241255867","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale: Novel therapeutic approaches are needed in stroke recovery. Whether pharmacological therapies are beneficial for enhancing stroke recovery is unclear. Dopamine is a neurotransmitter involved in motor learning, reward, and brain plasticity. Its prodrug levodopa is a promising agent for stroke recovery.
Aim and hypothesis: To investigate the hypothesis that levodopa, in addition to standardized rehabilitation therapy based on active task training, results in an enhancement of functional recovery in acute ischemic or hemorrhagic stroke patients compared to placebo.
Design: ESTREL (Enhancement of Stroke REhabilitation with Levodopa) is a randomized (ratio 1:1), multicenter, placebo-controlled, double-blind, parallel-group superiority trial.
Participants: 610 participants (according to sample size calculation) with a clinically meaningful hemiparesis will be enrolled ⩽7 days after stroke onset. Key eligibility criteria include (i) in-hospital-rehabilitation required, (ii) capability to participate in rehabilitation, (iii) previous independence in daily living.
Intervention: Levodopa 100 mg/carbidopa 25 mg three times daily, administered for 5 weeks in addition to standardized rehabilitation. The study intervention will be initiated within 7 days after stroke onset.
Comparison: Matching placebo plus standardized rehabilitation.
Outcomes: The primary outcome is the between-group difference of the Fugl-Meyer-Motor Assessment (FMMA) total score measured 3 months after randomization. Secondary outcomes include patient-reported health and wellbeing (PROMIS 10 and 29), patient-reported assessment of improvement, Rivermead Mobility Index, modified Rankin Scale, National Institutes of Health Stroke Scale (NIHSS), and as measures of harm: mortality, recurrent stroke, and serious adverse events.
Conclusion: The ESTREL trial will provide evidence of whether the use of Levodopa in addition to standardized rehabilitation in stroke patients leads to better functional recovery compared to rehabilitation alone.
期刊介绍：
Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.
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