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

Authors

• 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

Recommended Citation

Paganoni, Sabrina; Hendrix, Suzanne; Dickson, Samuel P.; Knowlton, Newman; Berry, James D.; Elliott, Michael A.; Maiser, Samuel; Karam, Chafic; Caress, James B.; Owegi, Margaret Ayo; Quick, Adam; Wymer, James; Goutman, Stephen A.; Heitzman, Daragh; Heiman-Patterson, Terry D.; Jackson, Carlayne; Quinn, Colin; Rothstein, Jeffrey D.; Kasarskis, Edward J.; Katz, Jonathan; Jenkins, Liberty; Ladha, Shafeeq S.; Miller, Timothy M.; Scelsa, Stephen N.; Vu, Tuan H.; Fournier, Christina; Johnson, Kristin M.; Swenson, Andrea; Goyal, Namita; Pattee, Gary L.; Babu, Suma; and Chase, Marianne, "Effect of sodium phenylbutyrate/taurursodiol on tracheostomy/ventilation-free survival and hospitalisation in amyotrophic lateral sclerosis: long-term results from the CENTAUR trial" (2022). Neurology. 1470.
https://scholar.barrowneuro.org/neurology/1470