Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial

Sabrina Paganoni, Harvard Medical School, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA spaganoni@mgh.harvard.edu.
Suzanne Hendrix, Pentara Corporation, Millcreek, Utah, USA.
Samuel P. Dickson, Pentara Corporation, Millcreek, Utah, USA.
Newman Knowlton, Pentara Corporation, Millcreek, Utah, USA.
James D. Berry, Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.
Michael A. Elliott, Swedish Neuroscience Institute, Seattle, Washington, USA.
Samuel Maiser, Department of Neurology, Hennepin Healthcare, Minneapolis, Minnesota, USA.
Chafic Karam, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
James B. Caress, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
Margaret Ayo Owegi, Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts, USA.
Adam Quick, Department of Neurology, Ohio State University, Columbus, Ohio, USA.
James Wymer, Department of Neurology, College of Medicine, University of Florida, Gainesville, Florida, USA.
Stephen A. Goutman, Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
Daragh Heitzman, ALS Clinic, Texas Neurology, Dallas, Texas, USA.
Terry D. Heiman-Patterson, Department of Neurology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania, USA.
Carlayne Jackson, Department of Neurology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
Colin Quinn, Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Jeffrey D. Rothstein, Department of Neurology, Johns Hopkins University Brain Science Institute, Baltimore, Maryland, USA.
Edward J. Kasarskis, Department of Neurology, University of Kentucky, Lexington, Kentucky, USA.
Jonathan Katz, California Pacific Medical Center Research Institute and Forbes Norris MDA/ALS Research and Treatment Center, San Francisco, California, USA.
Liberty Jenkins, California Pacific Medical Center Research Institute and Forbes Norris MDA/ALS Research and Treatment Center, San Francisco, California, USA.
Shafeeq S. Ladha, Department of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA.
Timothy M. Miller, Hope Center for Neurological Disorders, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA.
Stephen N. Scelsa, Department of Neurology, Mount Sinai Beth Israel, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Tuan H. Vu, Department of Neurology, University of South Florida Morsani College of Medicine, Tampa, Florida, USA.
Christina Fournier, Department of Neurology, Emory University, Atlanta, Georgia, USA.
Kristin M. Johnson, Department of Neurology, Ochsner Health System, New Orleans, Louisiana, USA.
Andrea Swenson, Department of Neurology, University of Iowa Health Care, Iowa City, Iowa, USA.
Namita Goyal, Department of Neurology, University of California Irvine School of Medicine, Irvine, California, USA.
Gary L. Pattee, Neurology Associates, Lincoln, Nebraska, USA.
Suma Babu, Harvard Medical School, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.
Marianne Chase, Harvard Medical School, Sean M. Healey and AMG Center for ALS & the Neurological Clinical Research Institute, Massachusetts General Hospital, Boston, Massachusetts, USA.

Document Type

Article

Abstract

BACKGROUND: Coformulated sodium phenylbutyrate/taurursodiol (PB/TURSO) was shown to prolong survival and slow functional decline in amyotrophic lateral sclerosis (ALS). OBJECTIVE: Determine whether PB/TURSO prolonged tracheostomy/ventilation-free survival and/or reduced first hospitalisation in participants with ALS in the CENTAUR trial. METHODS: Adults with El Escorial Definite ALS ≤18 months from symptom onset were randomised to PB/ TURSO or placebo for 6 months. Those completing randomised treatment could enrol in an open-label extension (OLE) phase and receive PB/TURSO for ≤30 months. Times to the following individual or combined key events were compared in the originally randomised treatment groups over a period spanning trial start through July 2020 (longest postrandomisation follow-up, 35 months): death, tracheostomy, permanent assisted ventilation (PAV) and first hospitalisation. RESULTS: Risk of any key event was 47% lower in those originally randomised to PB/TURSO (n=87) versus placebo (n=48, 71% of whom received delayed-start PB/TURSO in the OLE phase) (HR=0.53; 95% CI 0.35 to 0.81; p=0.003). Risks of death or tracheostomy/PAV (HR=0.51; 95% CI 0.32 to 0.84; p=0.007) and first hospitalisation (HR=0.56; 95% CI 0.34 to 0.95; p=0.03) were also decreased in those originally randomised to PB/TURSO. CONCLUSIONS: Early PB/TURSO prolonged tracheostomy/PAV-free survival and delayed first hospitalisation in ALS. TRIAL REGISTRATION NUMBER: NCT03127514; NCT03488524.

Publication Date

5-16-2022

Publication Title

Journal of neurology, neurosurgery, and psychiatry

E-ISSN

1468-330X

Volume

93

Issue

8

First Page

871

Last Page

5

PubMed ID

35577511

Digital Object Identifier (DOI)

10.1136/jnnp-2022-329024

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