Periodic Reporting for period 3 - BETTER-B (BETTER TREATMENTS FOR BREATHLESSNESS IN PALLIATIVE AND END OF LIFE CARE)
Periodo di rendicontazione: 2022-01-01 al 2023-06-30
The BETTER-B project focuses on breathlessness that persists despite optimal treatment of the underlying disease, usually referred to as chronic or refractory. This type of breathlessness is burdensome, neglected and yet one of the most common symptoms of advanced disease, estimated to affect 15 million people in Europe. Breathlessness can have a devastating impact on patients’ lives, and that of their family, friends and caregivers. Further, chronic breathlessness results in high health, social and informal care costs. New treatments for breathlessness are urgently needed as there is currently no widely licensed drug for the management of chronic breathlessness. An existing antidepressant, mirtazapine, has the potential to decrease chronic or refractory breathlessness in patients with advanced respiratory disease, in palliative care and at end of life. However, currently there is not robust evidence for mirtazapine’s use for this purpose. The overall objective of the BETTER-B project is to test whether mirtazapine is an effective and cost-effective medicine for the relief of patient-reported chronic or refractory breathlessness in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung diseases (ILD). Concurrently, the project maps and compare views, usual practice and experiences of palliative and respiratory clinicians across Europe on the main medications to alleviate breathlessness in COPD and ILD. A European wide survey of respiratory and palliative care physicians to explore current management of chronic breathlessness, and to determine the influence of practice guidance on management has been completed. The results have informed understanding of the feasibility of integrating mirtazapine in current clinical management, palliative and/or end of life and/or survivorship care regimes and healthcare systems across Europe. We are actively engaging with those affected by breathlessness across Europe to inform our plans and produce and disseminate European wide easily accessible guidance on the management of breathlessness in supportive, palliative and end of life care.
As part of WP1 survey led by UMK, we conducted a European wide survey of respiratory and palliative care physicians to explore current management of chronic breathlessness, and to determine the influence of practice guidance on management. We obtained ethical approval from the KCL Research Ethics Committee for the survey which included 450 responses and found a varied approach to breathlessness management across specialties, and across and within diseases. This variation in practice is not ethically acceptable and highlights the need for simpler accessible guidelines for breathlessness. Our results were shared at conferences and submitted for journal publication. A main WP1 paper was published open access online in BMC Pulmonary Medicine in Jan 2022. The survey findings have informed work relating to WP6 guidance.
We successfully opened all our originally planned 11 sites to recruitment. In order to mitigate the delays caused by COVID-19, Brexit and IMP sourcing, we opened an additional site in Mater Misericordiae University Hospital in Ireland, making a total of 12 opened sites. After four rounds of submission, we received regulatory approval and opened our Poland site in Sept 2022. UCSC Rome was also opened on 29th April 2022 following delays.
We had initially planned to end recruitment in July 2022. However, due to the COVID-19 pandemic, completion of some work packages have taken longer than expected and we requested and obtained another 6-month no-cost extension from 1/07/2023 to 31/12/2023 to allow for completion of these work packages.
Recruitment ended 31st Dec 2022 with a total of 273 participants (205 patients and 68 caregivers) recruited in Europe. We did not achieve our target sample size of 324 patients due to the COVID-19 pandemic, Brexit-related hurdles and other challenges previously discussed with the European Commission. The Australian team are conducting a parallel study and have recruited an additional 20 patients, which gives us a total of 225 patients (69%) for our analysis. We now have the largest trial of mirtazapine in our patient population.
U-MUEN with support from KCL, partners and the Ethics Advisory Board (EAB) have built an engaged network of patient, public and professional members. We have been guided by the EAB and our Patient and Public Involvement and Engagement (PPIE) members regarding how and in what form we share information on the project website. We have developed and translated factsheets for patients, and their families, to explain what will happen once a person goes into hospital with COVID-19, co-produced with our partners, the European Lung Foundation. We have also developed a guide to support people who suffer from breathlessness, who are managing their breathlessness at home, during the COVID-19 outbreak. Through Twitter, the guide has reached over 70,000 people from across the world.
As part of WP8, KCL have provided centralised project management across the consortium and have submitted all WP deliverables.
We successfully opened all our originally planned 11 sites to recruitment. In order to mitigate the delays caused by COVID-19, Brexit and IMP sourcing, we opened an additional site in Mater Misericordiae University Hospital in Ireland, making a total of 12 opened sites. After four rounds of submission, we received regulatory approval and opened our Poland site in Sept 2022. UCSC Rome was also opened on 29th April 2022 following delays.
We had initially planned to end recruitment in July 2022. However, due to the COVID-19 pandemic, completion of some work packages have taken longer than expected and we requested and obtained another 6-month no-cost extension from 1/07/2023 to 31/12/2023 to allow for completion of these work packages.
Recruitment ended 31st Dec 2022 with a total of 273 participants (205 patients and 68 caregivers) recruited in Europe. We did not achieve our target sample size of 324 patients due to the COVID-19 pandemic, Brexit-related hurdles and other challenges previously discussed with the European Commission. The Australian team are conducting a parallel study and have recruited an additional 20 patients, which gives us a total of 225 patients (69%) for our analysis. We now have the largest trial of mirtazapine in our patient population.
U-MUEN with support from KCL, partners and the Ethics Advisory Board (EAB) have built an engaged network of patient, public and professional members. We have been guided by the EAB and our Patient and Public Involvement and Engagement (PPIE) members regarding how and in what form we share information on the project website. We have developed and translated factsheets for patients, and their families, to explain what will happen once a person goes into hospital with COVID-19, co-produced with our partners, the European Lung Foundation. We have also developed a guide to support people who suffer from breathlessness, who are managing their breathlessness at home, during the COVID-19 outbreak. Through Twitter, the guide has reached over 70,000 people from across the world.
As part of WP8, KCL have provided centralised project management across the consortium and have submitted all WP deliverables.
There is currently a paucity of evidence-based treatments for breathlessness in palliative and end of life care.
Advances BETTER-B will bring about include:
• Timely testing of a new therapeutic option for a common symptom in palliative and end of life care, with robust data on its effectiveness and cost effectiveness;
• If mirtazapine is found to be effective, the potential to be of benefit to patients with many advanced conditions, and their families. It is available in all European countries at low cost. Equally, if mirtazapine is not cost-effective in patients with breathlessness, the findings will save resources as the results will enable decision makers to recommend that mirtazapine should not routinely be used for this patient group;
• Understanding whether mirtazapine is clinically and cost effective, will help to develop further interventions for breathlessness;
• The health economic components of our study will test methods of measuring cost effectiveness in this group, which will aid future studies, improving care;
• The largest randomised trial of mirtazapine on breathlessness in palliative and end of life care in the world to date;
• The potential to merge data with major trials in breathlessness being conducted by members of the consortium. Such a meta-analysis will provide unparalleled understanding of breathlessness and allow better comparisons of potential treatments;
• The development of a European wide collaborative between respiratory and palliative care that will be a platform for future studies
We have assembled a unique collaboration of diverse clinicians, researchers, health professionals and social scientists in five European countries to lead the BETTER-B project. Through our nine work packages, we expect our findings to have the following impacts:
• Reduced symptom burden and suffering or improved well-being of patients in need of palliative, end of life or survivorship care and of their formal and informal caregivers;
• Improved clinical guidance and policy recommendations;
• Improved quality, effectiveness and cost-effectiveness of palliative, end of life or survivorship care services as well as access to care;
• Reduced economic and wider societal burden arising from increased numbers of patients in need of palliative, end of life or survivorship care.
Advances BETTER-B will bring about include:
• Timely testing of a new therapeutic option for a common symptom in palliative and end of life care, with robust data on its effectiveness and cost effectiveness;
• If mirtazapine is found to be effective, the potential to be of benefit to patients with many advanced conditions, and their families. It is available in all European countries at low cost. Equally, if mirtazapine is not cost-effective in patients with breathlessness, the findings will save resources as the results will enable decision makers to recommend that mirtazapine should not routinely be used for this patient group;
• Understanding whether mirtazapine is clinically and cost effective, will help to develop further interventions for breathlessness;
• The health economic components of our study will test methods of measuring cost effectiveness in this group, which will aid future studies, improving care;
• The largest randomised trial of mirtazapine on breathlessness in palliative and end of life care in the world to date;
• The potential to merge data with major trials in breathlessness being conducted by members of the consortium. Such a meta-analysis will provide unparalleled understanding of breathlessness and allow better comparisons of potential treatments;
• The development of a European wide collaborative between respiratory and palliative care that will be a platform for future studies
We have assembled a unique collaboration of diverse clinicians, researchers, health professionals and social scientists in five European countries to lead the BETTER-B project. Through our nine work packages, we expect our findings to have the following impacts:
• Reduced symptom burden and suffering or improved well-being of patients in need of palliative, end of life or survivorship care and of their formal and informal caregivers;
• Improved clinical guidance and policy recommendations;
• Improved quality, effectiveness and cost-effectiveness of palliative, end of life or survivorship care services as well as access to care;
• Reduced economic and wider societal burden arising from increased numbers of patients in need of palliative, end of life or survivorship care.