Levodopa combined with standardized rehabilitation failed to improve motor recovery in stroke patients compared with placebo, with both groups experiencing similar rates of serious adverse events in a randomized trial of 610 participants.
The median Fugl-Meyer Assessment (FMA) score was 68 in the levodopa group and 64 in the placebo group at 3 months, with a mean difference of −0.90 points that was not statistically significant and fell well below the 6-point threshold considered clinically meaningful.
This double-blind, placebo-controlled ESTREL trial, published in JAMA Network, enrolled patients in Switzerland across 13 stroke units and centers and 11 rehabilitation centers between June 2019 and August 2024. Participants had ischemic or hemorrhagic stroke with clinically meaningful hemiparesis, defined as a score of at least three on motor items of the National Institutes of Health Stroke Scale (NIHSS). Patients were randomized 1:1 to receive levodopa/carbidopa 100 mg/25 mg (n = 307) or placebo (n = 303) 3 times daily for 39 days, in addition to standardized task-oriented rehabilitation. The primary outcome was motor recovery at 3 months, measured by the Fugl-Meyer Assessment (FMA) total score, which ranges from 0 to 100 points.
The median age of participants was 73 years, and 41% were female. The median baseline FMA score was 34 points. At 3 months, 28 participants had died, leaving 582 for the primary analysis.
Secondary outcomes also showed no difference between groups. PROMIS-29 scores averaged 66 in the levodopa group and 65 in the placebo group, while PROMIS-10 scores were 28 in both groups. Functional outcomes measured by the modified Rankin Scale, Rivermead Mobility Index, and NIHSS were comparable between the treatment groups. At 5 weeks, FMA scores were 57 in the levodopa group and 56 in the placebo group.
Adverse event rates were balanced, with 126 serious events in the levodopa group and 129 in the placebo group. Infections were most common, reported in 55 levodopa-treated and 44 placebo-treated patients. Prespecified adverse events of interest occurred in 79 patients receiving levodopa and 67 receiving placebo, with confusion and hallucinations most frequently noted.
“Study results oppose the idea of a benefit of levodopa-enhanced motor recovery suggested by a recent meta-analysisand do not support the reported practice of using levodopa to enhance stroke rehabilitation,” wrote lead study author Stefan T. Engelter, MD, of the Department of Rehabilitation and Neurology, University Department of Geriatric Medicine FELIX PLATTER, University of Basel, Basel, Switzerland, and colleagues.
Full disclosures can be found in the published study.
Source: JAMA
