DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial
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 qual...
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| Format: | Article |
| Language: | English |
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NIHR Journals Library
2016-06-01
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| Series: | Health Technology Assessment |
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| Online Access: | https://doi.org/10.3310/hta20450 |
| _version_ | 1828348394106519552 |
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| author | Christopher J McDermott Mike J Bradburn Chin Maguire Cindy L Cooper Wendy O Baird Susan K Baxter Judith Cohen 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 |
| author_facet | Christopher J McDermott Mike J Bradburn Chin Maguire Cindy L Cooper Wendy O Baird Susan K Baxter Judith Cohen 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 |
| author_sort | Christopher J McDermott |
| collection | DOAJ |
| description | 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. Trial registration: Current Controlled Trials ISRCTN53817913. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland. |
| first_indexed | 2024-04-14T00:53:36Z |
| format | Article |
| id | doaj.art-69ae3de3a3a84bfcbaa9492b27d7ef41 |
| institution | Directory Open Access Journal |
| issn | 1366-5278 2046-4924 |
| language | English |
| last_indexed | 2024-04-14T00:53:36Z |
| publishDate | 2016-06-01 |
| publisher | NIHR Journals Library |
| record_format | Article |
| series | Health Technology Assessment |
| spelling | doaj.art-69ae3de3a3a84bfcbaa9492b27d7ef412022-12-22T02:21:41ZengNIHR Journals LibraryHealth Technology Assessment1366-52782046-49242016-06-01204510.3310/hta2045009/55/33DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trialChristopher J McDermott0Mike J Bradburn1Chin Maguire2Cindy L Cooper3Wendy O Baird4Susan K Baxter5Judith Cohen6Hannah Cantrill7Simon Dixon8Roger Ackroyd9Simon Baudouin10Andrew Bentley11Richard Berrisford12Stephen Bianchi13Stephen C Bourke14Roy Darlison15John Ealing16Mark Elliott17Patrick Fitzgerald18Simon Galloway19Hisham Hamdalla20C Oliver Hanemann21Philip Hughes22Ibrahim Imam23Dayalan Karat24Roger Leek25Nick Maynard26Richard W Orrell27Abeezar Sarela28John Stradling29Kevin Talbot30Lyn Taylor31Martin Turner32Anita K Simonds33Tim Williams34Wisia Wedzicha35Carolyn Young36Pamela J Shaw37Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UKSheffield Clinical Trials Research Unit, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSheffield Clinical Trials Research Unit, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSheffield Clinical Trials Research Unit, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSchool of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSchool of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSheffield Clinical Trials Research Unit, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSheffield Clinical Trials Research Unit, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKHealth Economics and Decision Science, School of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKSheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield, UKRoyal Victoria Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust and the University of Newcastle, Newcastle upon Tyne, UKUniversity Hospital of South Manchester NHS Foundation Trust, Manchester, UKPlymouth Hospitals NHS Trust, Derriford Hospital, Plymouth, UKSheffield Teaching Hospitals NHS Foundation Trust, Royal Hallamshire Hospital, Sheffield, UKNorth Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust and Newcastle University, North Shields, UKIndependent patient and public involvement representative, UKSalford Royal Hospitals NHS Foundation Trust, Salford, UKLeeds Teaching Hospitals NHS Trust, St James’ University Hospital, Leeds, UKSchool of Health and Related Research (ScHARR), University of Sheffield, Sheffield, UKUniversity Hospital of South Manchester NHS Foundation Trust, Manchester, UKSalford Royal Hospitals NHS Foundation Trust, Salford, UKPlymouth University, Plymouth, UKPlymouth Hospitals NHS Trust Peninsula Medical and Dental Schools, Plymouth, UKSouth Devon Healthcare NHS Foundation Trust, Devon, UKNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UKMotor Neurone Disease Association, Birmingham, UKOxford University Hospitals NHS Trust, Oxford, UKThe National Heart and Lung Institute, Imperial College London, London, UKLeeds Teaching Hospitals NHS Trust, St James’ University Hospital, Leeds, UKOxford University Hospitals NHS Trust, Oxford, UKOxford University Hospitals NHS Trust, Oxford, UKPAREXEL International Corporation, Sheffield, UKOxford University Hospitals NHS Trust, Oxford, UKNational Institute for Health Research Respiratory Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust, London, UKNewcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UKThe National Heart and Lung Institute, Imperial College London, London, UKWalton Centre for Neurology & Neurosurgery NHS Foundation Trust, Liverpool, UKSheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UKBackground: 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. Trial registration: Current Controlled Trials ISRCTN53817913. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland.https://doi.org/10.3310/hta20450diaphragm pacingamyotrophic lateral sclerosisrandomised controlled trialrespiratory failureoverall survival |
| spellingShingle | Christopher J McDermott Mike J Bradburn Chin Maguire Cindy L Cooper Wendy O Baird Susan K Baxter Judith Cohen 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 DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial Health Technology Assessment diaphragm pacing amyotrophic lateral sclerosis randomised controlled trial respiratory failure overall survival |
| title | DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial |
| title_full | DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial |
| title_fullStr | DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial |
| title_full_unstemmed | DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial |
| title_short | DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis – a randomised controlled trial |
| title_sort | dipals diaphragm pacing in patients with amyotrophic lateral sclerosis a randomised controlled trial |
| topic | diaphragm pacing amyotrophic lateral sclerosis randomised controlled trial respiratory failure overall survival |
| url | https://doi.org/10.3310/hta20450 |
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