ESTREL-Fatigue-association of levodopa with post-stroke fatigue.
Boos L., Kaufmann JE., Sauter MI., Lyrer P., Zietz A., Trüssel S., Engelter SV., Luft AR., Polymeris A., Altersberger VL., Wiesner K., Held JPO., Rottenberger Y., Schwarz A., Medlin F., Accolla EA., Foucras S., Kägi G., De Marchis GM., Politz S., Greulich M., Tarnutzer AA., Sturzenegger R., Katan M., Fischer U., Nedeltchev K., Schär J., Deglon KVDK., Rapin P-A., Salerno A., Seiffge D., Auer E., Lippert J., Bonati LH., Schuster-Amft C., Gäumann S., Chabwine JN., Humm AM., Möller JC., Schweinfurther R., Bujan B., Jedrysiak P., Sandor PS., Gonzenbach R., Veit M., Lutz D., Lienert C., Peters N., Strambo D., Müri RM., Schädelin S., Hemkens LG., Ford GA., Kuppuswamy A., Lerdal A., Simpson DB., English C., Blackwell S., Gensicke H., Traenka C., Engelter ST.
INTRODUCTION: Post-stroke fatigue (PSF) is common and impacts stroke rehabilitation. Dopaminergic treatment may have beneficial effects on PSF. This study investigated whether levodopa, compared with placebo, was associated with a lower frequency or severity of PSF during in-hospital rehabilitation. PATIENTS AND METHODS: Enhancement of Stroke Rehabilitation with Levodopa (ESTREL)-Fatigue was an exploratory analysis of secondary outcome data obtained in the multicentre, randomised, placebo-controlled ESTREL trial. Participants with acute stroke received levodopa 100 mg/carbidopa 25 mg or placebo 3 times daily for 39 days to enhance motor recovery. Participants who (i) reported fatigue at 5 weeks and who (ii) took at least 80% of the study medication were included in ESTREL-Fatigue. No adjustments for confounding were made. The primary endpoint was the presence of PSF at 5 weeks, defined as a T-score of ≥ 55 on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short-form-4a. As secondary endpoints, T-score cutoffs of ≥ 60 (moderate fatigue) and ≥ 70 (severe fatigue) were used. Binary logistic regression was used to compare PSF at 5 weeks between treatment groups. Results are presented as odds ratios (ORs) with 95% CI. RESULTS: A total of 456 of 505 (90.3%) participants were included (levodopa/placebo 235/221, median age 73 years, 41% female). Post-stroke fatigue at 5 weeks was present in 63/235 (26.8%) levodopa-treated participants and in 65/221 (29.4%) placebo-treated participants (OR: 0.88; 95% CI, 0.58-1.32; risk ratio 0.91; risk difference - 2.6%). For cutoffs of ≥ 60 and ≥ 70, ORs were 0.78 (95% CI, 0.43-1.41) and 0.8 (95% CI, 0.25-2.44), respectively. A sensitivity analysis as per intention-to-treat with all 610 randomised ESTREL participants also showed no significant difference in fatigue presence between levodopa and placebo groups (OR: 0.95; 95% CI, 0.65-1.39) and a sensitivity analysis using a mixed-effects logistic regression showed no evidence of centre-related clustering. CONCLUSION: In ESTREL-Fatigue, levodopa, compared to placebo, was not associated with less PSF during in-hospital rehabilitation.