Long-term survival of participants in the CENTAUR trial of sodium phenylbutyrate-taurursodiol in amyotrophic lateral sclerosis.
CENTAUR
amyotrophic lateral sclerosis
motor neuron disease
sodium phenylbutyrate-taurursodiol
survival analysis
Journal
Muscle & nerve
ISSN: 1097-4598
Titre abrégé: Muscle Nerve
Pays: United States
ID NLM: 7803146
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
04
09
2020
revised:
07
10
2020
accepted:
09
10
2020
pubmed:
17
10
2020
medline:
20
2
2021
entrez:
16
10
2020
Statut:
ppublish
Résumé
An orally administered, fixed-dose coformulation of sodium phenylbutyrate-taurursodiol (PB-TURSO) significantly slowed functional decline in a randomized, placebo-controlled, phase 2 trial in ALS (CENTAUR). Herein we report results of a long-term survival analysis of participants in CENTAUR. In CENTAUR, adults with ALS were randomized 2:1 to PB-TURSO or placebo. Participants completing the 6-month (24-week) randomized phase were eligible to receive PB-TURSO in the open-label extension. An all-cause mortality analysis (35-month maximum follow-up post-randomization) incorporated all randomized participants. Participants and site investigators were blinded to treatment assignments through the duration of follow-up of this analysis. Vital status was obtained for 135 of 137 participants originally randomized in CENTAUR. Median overall survival was 25.0 months among participants originally randomized to PB-TURSO and 18.5 months among those originally randomized to placebo (hazard ratio, 0.56; 95% confidence interval, 0.34-0.92; P = .023). Initiation of PB-TURSO treatment at baseline resulted in a 6.5-month longer median survival as compared with placebo. Combined with results from CENTAUR, these results suggest that PB-TURSO has both functional and survival benefits in ALS.
Identifiants
pubmed: 33063909
doi: 10.1002/mus.27091
pmc: PMC7820979
doi:
Substances chimiques
Neuroprotective Agents
0
Phenylbutyrates
0
Taurochenodeoxycholic Acid
516-35-8
ursodoxicoltaurine
60EUX8MN5X
4-phenylbutyric acid
7WY7YBI87E
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
31-39Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR001414
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001420
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.
Références
Am J Manag Care. 2020 Aug;26(9 Suppl):S198-S205
pubmed: 32840333
Amyotroph Lateral Scler Frontotemporal Degener. 2020 Nov;21(7-8):509-518
pubmed: 32573277
Amyotroph Lateral Scler Frontotemporal Degener. 2018 May;19(3-4):206-211
pubmed: 29260911
Neuropsychopharmacology. 2009 Jun;34(7):1721-32
pubmed: 19145227
Mol Omics. 2018 Feb 1;14(1):53-63
pubmed: 29570205
Am Rev Respir Dis. 1983 Jun;127(6):725-34
pubmed: 6859656
N Engl J Med. 1994 Mar 3;330(9):585-91
pubmed: 8302340
PLoS One. 2013;8(2):e56047
pubmed: 23424643
Amyotroph Lateral Scler. 2009 Apr;10(2):99-106
pubmed: 18688762
N Engl J Med. 2020 Sep 3;383(10):919-930
pubmed: 32877582
Neurobiol Dis. 2016 Jun;90:35-42
pubmed: 26282323
Cells. 2019 Nov 20;8(12):
pubmed: 31757001
Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):610-7
pubmed: 25286015
Cell Death Dis. 2018 Feb 28;9(3):333
pubmed: 29491369
J Neurochem. 2005 Jun;93(5):1087-98
pubmed: 15934930
BMC Public Health. 2012 Aug 07;12:621
pubmed: 22871071
Curr Control Trials Cardiovasc Med. 2002 Jan 8;3(1):4
pubmed: 11985778
Clin Investig (Lond). 2014;4(7):605-618
pubmed: 28203356
Expert Opin Investig Drugs. 2001 Jul;10(7):1243-53
pubmed: 11772248
Eur J Neurol. 2016 Jan;23(1):45-52
pubmed: 25664595
N Engl J Med. 2017 Jul 13;377(2):162-172
pubmed: 28700839
Neurobiol Aging. 2015 Jan;36(1):228-40
pubmed: 25443293
Muscle Nerve. 2021 Jan;63(1):31-39
pubmed: 33063909
Aging Cell. 2011 Jun;10(3):418-28
pubmed: 21272191
Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9
pubmed: 11464847
Ann Clin Transl Neurol. 2016 Sep 07;3(11):866-875
pubmed: 27844032
Neurology. 2013 Oct 8;81(15):1350-5
pubmed: 24005339
Cell Death Dis. 2018 Feb 28;9(3):327
pubmed: 29491392
J Biol Chem. 2011 Dec 30;286(52):45083-92
pubmed: 22069317
J Neurol Neurosurg Psychiatry. 2016 Jun;87(6):628-32
pubmed: 26152368
PLoS One. 2014 Nov 07;9(11):e110086
pubmed: 25379658
Lancet. 1996 May 25;347(9013):1425-31
pubmed: 8676624
Evid Based Spine Care J. 2011 Feb;2(1):7-10
pubmed: 22956930
BMC Cancer. 2017 Sep 2;17(1):611
pubmed: 28865422
Lancet Neurol. 2017 Jul;16(7):505-512
pubmed: 28522181
Transl Neurodegener. 2017 Sep 26;6:25
pubmed: 29021896