TOPLINE:

Levodopa added to standard inpatient rehabilitation therapy was not associated with greater improvement in motor recovery at 3 months compared with matching placebo in patients with acute or hemorrhagic stroke, new results from the ESTREL trial showed.

METHODOLOGY:

• The double-blind, placebo-controlled ESTREL trial was conducted in 13 stroke units/centers and 11 rehab centers in Switzerland between 2019 and 2024.
• More than 600 participants (median age, 73 years; 59% men) with acute ischemic or hemorrhagic stroke and clinically meaningful hemiparesis were randomly assigned about 1:1 to receive levodopa/carbidopa (100 mg/25 mg) or a matching placebo up to three times per day for 39 days, along with standardized task-oriented rehabilitation.
• The primary outcome was the adjusted mean difference in Fugl-Meyer Assessment (FMA) total score at 3 months between groups, with lower scores indicating worse motor function.
• Other measures included the Patient-Reported Outcomes Measurement Information System, modified Rankin Scale, National Institutes of Health Stroke Scale, Rivermead Mobility Index scores, patient-reported outcomes, and safety.

TAKEAWAY:

• At 3 months, FMA total scores were not significantly different between the levodopa and placebo groups (mean group difference, -0.9).
• No significant differences were observed between groups for any secondary outcomes, including FMA upper extremity and lower extremity scores.
• Serious adverse events (AEs) were similar between groups, with 126 in the levodopa group and 129 in the placebo group.
• Infection was the most common AE (n = 55 vs 44, respectively). Among prespecified AEs, confusion was most frequent in the levodopa group, and hallucinations were most frequent in the placebo group.

IN PRACTICE:

The investigators wrote that, despite its potential to enhance neuroplasticity, the findings “do not support the use of levodopa as an adjunct to rehabilitation therapy for enhancing motor recovery after acute stroke.”

SOURCE:

The study was led by Stefan T. Engelter, MD, University of Basel, Basel, Switzerland. It was published online on September 22 in JAMA.

LIMITATIONS:

The trial was conducted exclusively in Switzerland, which may have limited the generalizability of the findings. FMA interrater reliability was not systematically evaluated, and levodopa serum levels were not measured, leaving pharmacokinetic variability unassessed. The study did not account for genetic modifiers of treatment response. Additionally, therapy homogeneity across centers was not assessed, and potential effects on nonmotor poststroke conditions such as fatigue or depression were not evaluated.

DISCLOSURES:

The study was funded by the Swiss National Science Foundation. Several investigators reported having financial or other ties with various sources. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.