Christopher J. McDermott
DiPALS: Diaphragm pacing in patients with amyotrophic lateral sclerosis – A randomised controlled trial
McDermott, Christopher J.; Bradburn, Mike J.; Maguire, Chin; Cooper, Cindy L.; Baird, Wendy O.; Baxter, Susan K.; Cohen, Judith; Cantrill, Hannah; Dixon, Simon; Ackroyd, Roger; Baudouin, Simon; Bentley, Andrew; Berrisford, Richard; Bianchi, Stephen; Bourke, Stephen C.; Darlison, Roy; Ealing, John; Elliott, Mark; Fitzgerald, Patrick; Galloway, Simon; Hamdalla, Hisham; Hanemann, C. Oliver; Hughes, Philip; Imam, Ibrahim; Karat, Dayalan; Leek, Roger; Maynard, Nick; Orrell, Richard W.; Sarela, Abeezar; Stradling, John; Talbot, Kevin; Taylor, Lyn; Turner, Martin; Simonds, Anita K.; Williams, Tim; Wedzicha, Wisia; Young, Carolyn; Shaw, Pamela J.
Authors
Mike J. Bradburn
Chin Maguire
Cindy L. Cooper
Wendy O. Baird
Susan K. Baxter
Professor Judith Cohen J.Cohen@hull.ac.uk
Director, Hull Health Trials Unit
Hannah Cantrill
Simon Dixon
Roger Ackroyd
Simon Baudouin
Andrew Bentley
Richard Berrisford
Stephen Bianchi
Stephen C. Bourke
Roy Darlison
John Ealing
Mark Elliott
Patrick Fitzgerald
Simon Galloway
Hisham Hamdalla
C. Oliver Hanemann
Philip Hughes
Ibrahim Imam
Dayalan Karat
Roger Leek
Nick Maynard
Richard W. Orrell
Abeezar Sarela
John Stradling
Kevin Talbot
Lyn Taylor
Martin Turner
Anita K. Simonds
Tim Williams
Wisia Wedzicha
Carolyn Young
Pamela J. Shaw
Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2–3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4® diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure.
Objective
The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure.
Design
The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy.
Participants
Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation.
Interventions
Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS.
Main outcome measures
The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost–utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy.
Results
In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01).
Conclusions
Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure.
Future work
It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further.
Citation
McDermott, C. J., Bradburn, M. J., Maguire, C., Cooper, C. L., Baird, W. O., Baxter, S. K., Cohen, J., Cantrill, H., Dixon, S., Ackroyd, R., Baudouin, S., Bentley, A., Berrisford, R., Bianchi, S., Bourke, S. C., Darlison, R., Ealing, J., Elliott, M., Fitzgerald, P., Galloway, S., …Shaw, P. J. (2016). DiPALS: Diaphragm pacing in patients with amyotrophic lateral sclerosis – A randomised controlled trial. Health Technology Assessment, 20(45), 1-218. https://doi.org/10.3310/hta20450
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 4, 2016 |
Publication Date | Jun 1, 2016 |
Deposit Date | Nov 14, 2018 |
Publicly Available Date | Nov 14, 2018 |
Journal | Health Technology Assessment |
Print ISSN | 1366-5278 |
Publisher | NIHR Journals Library |
Peer Reviewed | Peer Reviewed |
Volume | 20 |
Issue | 45 |
Pages | 1-218 |
DOI | https://doi.org/10.3310/hta20450 |
Keywords | Health Policy |
Public URL | https://hull-repository.worktribe.com/output/785063 |
Publisher URL | https://www.journalslibrary.nihr.ac.uk/hta/hta20450/#/full-report |
Additional Information | Contractual start date: 07-2011; Editorial review begun: 07-2015; Accepted for publication: 01-2016 |
Contract Date | Nov 14, 2018 |
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© Queen’s Printer and Controller of HMSO 2016. This work was produced by McDermottet al.under the terms of acommissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes ofprivate research and study and extracts (or indeed, the full report) may be included in professional journals provided thatsuitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications forcommercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trialsand Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK.
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