Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial-Reference-Cited by-同舟云学术

Enhancement of STroke REhabilitation with Levodopa (ESTREL): Rationale and design of a randomized placebo-controlled, double blind superiority trial

Published:2024-06-09 Issue: Volume: Page:
ISSN:2396-9873
Container-title:European Stroke Journal
language:en
Short-container-title:European Stroke Journal

Author:

Zietz Annaelle¹²^ORCID,Kaufmann Josefin E¹²^ORCID,Wiesner Karin¹²,Fischer Sandro Kevin¹²,Wiegert Martina¹²,Verhagen-Kamerbeek Wilma DJ¹²,Rottenberger Yannik³,Schwarz Anne³^ORCID,Peters Nils¹²⁴,Gensicke Henrik¹²,Medlin Friedrich⁵,Möller Jens Carsten⁶,Bujan Bartosz⁷,Bonati Leo H²⁸,Arnold Marcel⁹,Schaedelin Sabine¹⁰,Müri René M.⁹,Hemkens Lars G¹⁰¹¹¹²¹³,Michel Patrik¹⁴,Lyrer Philippe A²,Held Jeremia P³¹⁵,Ford Gary A¹⁶,Luft Andreas R³¹⁷,Traenka Christopher¹²,Engelter Stefan T¹²

Affiliation:

1. Neurology and Neurorehabilitation, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland

2. Department of Neurology and Stroke Center, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland

3. Department of Neurology, University and University Hospital of Zurich, Zurich, Switzerland

4. Stroke Center, Klinik Hirslanden, Zürich, Switzerland

5. Stroke Unit, Cantonal Hospital Fribourg, Fribourg, Switzerland

6. Center for Neurological Rehabilitation, Zihlschlacht, Switzerland

7. Neurorehabilitation, Klinik Lengg Zürich, Zurich, Switzerland

8. Research Department, Rheinfelden Rehabilitation Clinic, Switzerland

9. Department of Neurology, University Hospital Inselspital, Bern, Switzerland

10. Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland

11. Pragmatic Evidence Lab, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland

12. Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA

13. Meta-Research Innovation Center Berlin (METRIC-B), Berlin Institute of Health, Berlin, Germany

14. Stroke Center, Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland

15. Rehabilitation Triemli Zurich, Valens Clinics, Zurich, Switzerland

16. Oxford University Hospitals NHS Foundation Trust, University of Oxford, Oxford, UK

17. Cereneo, Center for Neurology and Rehabilitation, Vitznau, Switzerland

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.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

Science Funds Rehabilitation of the University Geriatric Medicine FELIX PLATTER, University of Basel, Switzerland

Schweizerische Herzstiftung

Publisher

SAGE Publications

Link

https://journals.sagepub.com/doi/pdf/10.1177/23969873241255867

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