{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T02:14:12Z","timestamp":1777083252095,"version":"3.51.4"},"reference-count":20,"publisher":"BMJ","issue":"10","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Neurol Neurosurg Psychiatry"],"accepted":{"date-parts":[[2019,6,10]]},"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To evaluate the efficacy and safety of oral levosimendan in patients with amyotrophic lateral sclerosis (ALS). This phase II, randomised, double-blind, placebo-controlled, crossover, three-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60%\u201390 % of predicted from 11 sites in four countries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients received levosimendan 1\u2009mg daily, 1\u2009mg two times a day or placebo during three 14-day crossover periods and levosimendan 1\u20132\u2009mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale-Revised (ALSFRS-R), tolerability and safety.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 66 patients randomised, 59 contributed to the double-blind results and 50 entered open-label follow-up. Sitting SVC was not significantly different between the treatments. In post hoc analysis using period-wise baselines, supine SVC favoured levosimendan over placebo, estimated mean differences from baseline being \u22123.62% on placebo, +0.77% on levosimendan 1\u2009mg daily (p=0.018) and +2.38% on 1\u2009mg two times a day (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1\u2009mg daily (p=0.030), 28.6% during 1\u2009mg two times a day (p=0.002) and 3.3% during placebo. The respective frequencies for increased heart rate were 5.1% (p=0.337), 18.5% (p=0.018) and 1.7%. No significant differences between the treatments were seen for other adverse events.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Levosimendan did not achieve the primary endpoint of improving sitting SVC in ALS. Headache and increased heart rate were increased on levosimendan, although it was otherwise well tolerated. 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