FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3199546106> ?p ?o ?g. }

• W3199546106 endingPage "831" @default.
• W3199546106 startingPage "821" @default.
• W3199546106 abstract "There is an urgent unmet need for new therapies in amyotrophic lateral sclerosis. In a clinical study with healthy volunteers, levosimendan, a calcium sensitiser, was shown to improve neuromechanical efficiency and contractile function of the human diaphragm. We aimed to evaluate the safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis, with a focus on respiratory function.The REFALS study is a randomised, double-blind, placebo-controlled phase 3 trial at 99 amyotrophic lateral sclerosis specialist centres in 14 countries worldwide. People with amyotrophic lateral sclerosis were eligible for participation if they were at least 18 years of age and had a sitting slow vital capacity (SVC) of 60-90% predicted. Participants were randomly assigned (2:1) by interactive web-response system to receive either levosimendan or placebo. The capsules for oral administration were identical in appearance to maintain blinding of participants and investigators. The primary endpoint was the change from baseline in supine SVC at 12 weeks, assessed as the percentage of predicted normal sitting SVC. The key secondary endpoint was the combined assessment of function and survival (CAFS) up to 48 weeks. Analyses were done in the intention-to-treat population, comprising all participants who were randomly assigned. This trial is registered at ClinicalTrials.gov (NCT03505021) and has been completed. An extension study (REFALS-ES; NCT03948178) has also been completed, but will be reported separately.Between June 21, 2018, and June 28, 2019, 871 people were screened for the study, of whom 496 were randomly assigned either levosimendan (n=329) or placebo (n=167). Participants were followed up between June 27, 2018 and June 26, 2020, for a median duration of 50·1 (IQR 37·5-51·1) weeks. The median duration of treatment was 47·9 (IQR 26·4-48·1) weeks. Change from baseline in supine SVC at 12 weeks was -6·73% with levosimendan and -6·99% with placebo, with no significant difference between the treatments (estimated treatment difference 0·26%, 95% CI -2·03 to 2·55, p=0·83). Similarly, at week 48, CAFS did not differ between treatment groups (least squares mean change from baseline 10·69, 95% CI -15·74 to 37·12; nominal p value=0·43). The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%]). 33 (10%) participants allocated levosimendan and 20 (12%) assigned placebo died during the trial, mainly due to respiratory failure or progression of amyotrophic lateral sclerosis.Levosimendan was not superior to placebo in maintaining respiratory function in a broad population with amyotrophic lateral sclerosis. Although levosimendan was generally well tolerated, increased heart rate and headache occurred more frequently with levosimendan than with placebo. The possibility of a clinically relevant subgroup of responsive individuals requires further evaluation.Orion Corporation." @default.
• W3199546106 created "2021-09-27" @default.
• W3199546106 creator A5000794291 @default.
• W3199546106 creator A5001304246 @default.
• W3199546106 creator A5001954609 @default.
• W3199546106 creator A5002714845 @default.
• W3199546106 creator A5003172727 @default.
• W3199546106 creator A5005633849 @default.
• W3199546106 creator A5008361526 @default.
• W3199546106 creator A5008484351 @default.
• W3199546106 creator A5009548490 @default.
• W3199546106 creator A5010342160 @default.
• W3199546106 creator A5011065516 @default.
• W3199546106 creator A5013892887 @default.
• W3199546106 creator A5014788047 @default.
• W3199546106 creator A5015861848 @default.
• W3199546106 creator A5016261929 @default.
• W3199546106 creator A5018020880 @default.
• W3199546106 creator A5020349857 @default.
• W3199546106 creator A5020442716 @default.
• W3199546106 creator A5020879974 @default.
• W3199546106 creator A5021958762 @default.
• W3199546106 creator A5022326820 @default.
• W3199546106 creator A5023448259 @default.
• W3199546106 creator A5023627853 @default.
• W3199546106 creator A5024570101 @default.
• W3199546106 creator A5025380289 @default.
• W3199546106 creator A5026477817 @default.
• W3199546106 creator A5027886510 @default.
• W3199546106 creator A5028073978 @default.
• W3199546106 creator A5029639314 @default.
• W3199546106 creator A5030609927 @default.
• W3199546106 creator A5030730290 @default.
• W3199546106 creator A5031853409 @default.
• W3199546106 creator A5031921927 @default.
• W3199546106 creator A5032499419 @default.
• W3199546106 creator A5032907512 @default.
• W3199546106 creator A5033276432 @default.
• W3199546106 creator A5035602637 @default.
• W3199546106 creator A5037236039 @default.
• W3199546106 creator A5039827008 @default.
• W3199546106 creator A5040679500 @default.
• W3199546106 creator A5040797978 @default.
• W3199546106 creator A5043129865 @default.
• W3199546106 creator A5044584675 @default.
• W3199546106 creator A5046276536 @default.
• W3199546106 creator A5046488842 @default.
• W3199546106 creator A5047905281 @default.
• W3199546106 creator A5048588036 @default.
• W3199546106 creator A5049803861 @default.
• W3199546106 creator A5051182549 @default.
• W3199546106 creator A5051877073 @default.
• W3199546106 creator A5052581382 @default.
• W3199546106 creator A5052630833 @default.
• W3199546106 creator A5052739733 @default.
• W3199546106 creator A5052763751 @default.
• W3199546106 creator A5053264151 @default.
• W3199546106 creator A5053813711 @default.
• W3199546106 creator A5055043449 @default.
• W3199546106 creator A5055212192 @default.
• W3199546106 creator A5056240044 @default.
• W3199546106 creator A5056671297 @default.
• W3199546106 creator A5056969742 @default.
• W3199546106 creator A5057016612 @default.
• W3199546106 creator A5057195222 @default.
• W3199546106 creator A5057215950 @default.
• W3199546106 creator A5057546392 @default.
• W3199546106 creator A5058244935 @default.
• W3199546106 creator A5059455936 @default.
• W3199546106 creator A5059968968 @default.
• W3199546106 creator A5061008360 @default.
• W3199546106 creator A5061347020 @default.
• W3199546106 creator A5061360903 @default.
• W3199546106 creator A5062379807 @default.
• W3199546106 creator A5063229609 @default.
• W3199546106 creator A5063719862 @default.
• W3199546106 creator A5065494227 @default.
• W3199546106 creator A5067017137 @default.
• W3199546106 creator A5068656707 @default.
• W3199546106 creator A5068904843 @default.
• W3199546106 creator A5070475275 @default.
• W3199546106 creator A5071062652 @default.
• W3199546106 creator A5071868715 @default.
• W3199546106 creator A5072517614 @default.
• W3199546106 creator A5074064047 @default.
• W3199546106 creator A5074360463 @default.
• W3199546106 creator A5075024436 @default.
• W3199546106 creator A5075435812 @default.
• W3199546106 creator A5076109679 @default.
• W3199546106 creator A5076278333 @default.
• W3199546106 creator A5077048801 @default.
• W3199546106 creator A5080276406 @default.
• W3199546106 creator A5080435150 @default.
• W3199546106 creator A5082524383 @default.
• W3199546106 creator A5082795436 @default.
• W3199546106 creator A5083309896 @default.
• W3199546106 creator A5084044892 @default.
• W3199546106 creator A5084777911 @default.

• next