Engelter Stefan T, Kaufmann Josefin E, Zietz Annaelle, Luft Andreas R, Polymeris Alexandros, Altersberger Valerian L, Wiesner Karin, Wiegert Martina, Held Jeremia P O, Rottenberger Yannik, Schwarz Anne, Medlin Friedrich, Accolla Ettore A, Foucras Sandrine, Kägi Georg, De Marchis Gian Marco, Politz Svetlana, Greulich Matthias, Tarnutzer Alexander A, Sturzenegger Rolf, Katan Mira, Fischer Urs, Nedeltchev Krassen, Schär Janine, Van Den Keybus Deglon Katrien, Rapin Pierre-André, Salerno Alexander, Seiffge David J, Auer Elias, Lippert Julian, Bonati Leo H, Schuster-Amft Corina, Gäumann Szabina, Chabwine Joelle N, Humm Andrea, Möller J Carsten, Schweinfurther Raoul, Bujan Bartosz, Jedrysiak Piotr, Sandor Peter S, Gonzenbach Roman, Mylius Veit, Lutz Dietmar, Lienert Carmen, Peters Nils, Michel Patrik, Müri René M, Schädelin Sabine, Hemkens Lars G, Ford Gary A, Lyrer Philippe A, Gensicke Henrik, Traenka Christopher
Department of Rehabilitation and Neurology, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland.
Department of Neurology and Stroke Center, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
JAMA. 2025 Sep 22. doi: 10.1001/jama.2025.15185.
Levodopa enhances dopaminergic signaling and may stimulate neuroplasticity, which could potentially enhance motor recovery after stroke. Levodopa is used in stroke rehabilitation despite mixed evidence for its effectiveness.
To determine whether levodopa compared with placebo, administered in addition to standardized rehabilitation based on active task-oriented training, is associated with enhanced motor recovery in patients with acute stroke.
DESIGN, SETTING, AND PARTICIPANTS: A double-blind, placebo-controlled randomized clinical trial at 13 stroke units and centers and 11 collaborating rehabilitation centers in Switzerland. Between June 14, 2019 (first patient, first visit), and August 27, 2024 (last patient, last visit), 610 patients with acute ischemic or hemorrhagic stroke with clinically meaningful hemiparesis (ie, a total score of ≥3 points on the following National Institutes of Health Stroke Scale items: motor arm, motor leg, or limb ataxia) were randomized 1:1 to receive levodopa or placebo. Statistical analyses were conducted from November 2024 to August 2025.
Patients received levodopa/carbidopa (100 mg/25 mg; n = 307) or placebo (n = 303) 3 times daily for 39 days, alongside standardized rehabilitation therapy based on active task-oriented training.
The primary outcome was the adjusted mean between-group difference in the Fugl-Meyer Assessment (FMA) total score (range, 0-100 points; fewer points indicate worse motor function; 6-point difference considered patient-relevant) at 3 months.
Among the 610 participants (median [IQR] age, 73 [64-82] years; 252 [41.3%] female; median baseline FMA total score, 34 [14-54]), 28 participants died by 3 months, leaving 582 (95.4%) participants eligible for the primary analysis. At 3 months, the median (IQR) FMA total score was 68 (42-85) points in the levodopa group and 64 (44-83) points in the placebo group. The mean difference in the FMA total score between the levodopa and placebo groups was -0.90 points (95% CI, -3.78 to 1.98; P = .54). There were 126 serious adverse events in the levodopa group and 129 in the placebo group; the most common was infection (levodopa, n = 55; placebo, n = 44).
In this randomized clinical trial, among patients receiving inpatient rehabilitation for acute stroke, levodopa added to standardized rehabilitation did not significantly improve motor function at 3 months compared with placebo plus standardized rehabilitation. These results do not support the use of levodopa as an adjunct to rehabilitation therapy for enhancing motor recovery after acute stroke.
ClinicalTrials.gov Identifier: NCT03735901.
左旋多巴可增强多巴胺能信号传导，并可能刺激神经可塑性，这有可能促进中风后的运动恢复。尽管其有效性的证据不一，但左旋多巴仍用于中风康复治疗。
确定在基于主动任务导向训练的标准化康复治疗基础上，与安慰剂相比，给予左旋多巴是否能使急性中风患者的运动恢复得到增强。
设计、地点和参与者：在瑞士的13个中风单元和中心以及11个合作康复中心进行的一项双盲、安慰剂对照随机临床试验。在2019年6月14日（首例患者首次就诊）至2024年8月27日（末例患者末次就诊）期间，610例急性缺血性或出血性中风且伴有具有临床意义的偏瘫患者（即美国国立卫生研究院卒中量表以下项目总分≥3分：上肢运动、下肢运动或肢体共济失调）被随机分为1:1两组，分别接受左旋多巴或安慰剂治疗。统计分析于2024年11月至2025年8月进行。
患者每天服用3次左旋多巴/卡比多巴（100毫克/25毫克；n = 307）或安慰剂（n = 303），持续39天，同时接受基于主动任务导向训练的标准化康复治疗。
主要结局是3个月时Fugl - Meyer评估（FMA）总分（范围为0 - 100分；分数越低表明运动功能越差；6分的差异被认为与患者相关）的调整组间平均差异。
在610名参与者中（年龄中位数[四分位间距]为73[64 - 82]岁；252名[41.3%]为女性；基线FMA总分中位数为34[14 - 54]），28名参与者在3个月内死亡，剩余582名（95.4%）参与者符合主要分析条件。3个月时，左旋多巴组FMA总分中位数（四分位间距）为68（42 - 85）分，安慰剂组为64（44 - 83）分。左旋多巴组和安慰剂组FMA总分的平均差异为 - 0.90分（95%置信区间， - 3.78至1.98；P = 0.54）。左旋多巴组有126例严重不良事件，安慰剂组有129例；最常见的是感染（左旋多巴组，n = 55；安慰剂组，n = 44）。
在这项随机临床试验中，对于接受急性中风住院康复治疗的患者，与安慰剂加标准化康复治疗相比，左旋多巴加标准化康复治疗在3个月时并未显著改善运动功能。这些结果不支持将左旋多巴用作康复治疗的辅助手段以增强急性中风后的运动恢复。
ClinicalTrials.gov标识符：NCT03735901。
