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Oral Levosimendan in amyotrophic lateral sclerosis: a phase II multicentre, randomised, double-blind, placebo-controlled trial

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Version 2 2023-06-12, 09:10
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posted on 2023-06-12, 09:10 authored by Ammar Al-Chalabi, Pamela Shaw, Nigel LeighNigel Leigh, Leonard van den Berg, Orla Hardiman, Albert Ludolph, Valtteri V Aho, Toni Sarapohja, Mikko Kuoppamäki
Objective To evaluate the efficacy and safety of oral levosimendan in amyotrophic lateral sclerosis (ALS) patients. This phase 2, randomised, double-blind, placebo-controlled, crossover, 3-period study with 6 months open-label follow-up enrolled adults with ALS and sitting slow vital capacity (SVC) 60-90% of predicted from 11 sites in four countries. Methods Patients received levosimendan 1 mg daily, 1 mg bd or placebo during three 14-day crossover periods, and levosimendan 1-2 mg daily during open-label follow-up. Primary endpoint was sitting SVC; secondary endpoints included supine SVC, ALS Functional Rating Scale (ALSFRS-R), tolerability and safety. Results 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 -3.62% on placebo, +0.77% on levosimendan 1 mg daily (p=0.018) and +2.38% on 1 mg bd (p=0.001). Headache occurred in 16.7% of patients during levosimendan 1 mg daily (p=0.030), 28.6% during 1 mg bd (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. Conclusions 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. A phase 3 study to evaluate the longer-term effects of oral levosimendan in ALS is ongoing.

History

Publication status

  • Published

File Version

  • Published version

Journal

Journal of Neurology, Neurosurgery and Psychiatry

ISSN

0022-3050

Publisher

BMJ Publishing Group

Issue

10

Volume

90

Page range

1165-1170

Department affiliated with

  • BSMS Neuroscience Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-07-05

First Open Access (FOA) Date

2019-07-24

First Compliant Deposit (FCD) Date

2019-07-05

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