Abstract
Introduction One-fifth of emergency department presentations by ambulance are due to acute-on-chronic breathlessness. We explored the feasibility of an evaluation-phase, cluster randomised controlled trial (cRCT) of the effectiveness and cost-effectiveness of a paramedic-administered, non-pharmacological breathlessness intervention for people with acute-on-chronic breathlessness at ambulance call-out (BREATHE) regarding breathlessness intensity and conveyance to hospital.
Methods This mixed-methods, feasibility cRCT (ISRCTN80330546) randomised paramedics to usual care or intervention plus usual care. Retrospective patient consent to use call-out data (primary end-point) and prospective patient/carer consent for follow-up was sought. Potential primary outcomes included breathlessness intensity (numerical rating scale) and conveyance. Follow-up included: interviews with patients/carers and questionnaires at 14 days, 1 and 6 months; paramedic focus groups and surveys.
Results Recruitment was during COVID-19, with high demands on paramedics and fewer call-outs by eligible patients. We enrolled 29 paramedics; nine withdrew. Randomisation/trial procedures were acceptable. Paramedics recruited 13 patients, not meeting recruitment target (n=36); eight patients and three carers were followed-up. Data quality was good but insufficient for future sample size estimation. The intervention did not extend call-out time, was delivered with fidelity and was acceptable to patients, carers and paramedics. There were no repeat call-outs within 48 h. All trained paramedics strongly recommended BREATHE as a highly relevant, simple intervention.
Conclusion Patient recruitment to target was not feasible during the pandemic. Training and intervention were acceptable and delivered with fidelity. Results include valuable information on recruitment, consent, attrition and data collection that will inform the design and delivery of a definitive trial.
Abstract
A paramedic-delivered BREATHE intervention for acute-on-chronic breathlessness and study procedures were acceptable but recruitment was low (pandemic related); further work is necessary to answer remaining questions on sample size and best primary outcome https://bit.ly/3AsNQZ5
Introduction
Chronic (persistent) breathlessness – disabling despite treatment of underlying causes [1] – is prevalent in cardiorespiratory disease(s), and acute exacerbations are frightening for patients and carers. It is more common in older adults [2] with widespread impacts for patients, family carers and health systems [1–3]. Acute worsening of chronic breathlessness (acute-on-chronic breathlessness [4]) is mostly triggered by physical and/or emotional exertion but can relate to worsening of the underlying cause(s) [5]. Non-pharmacological interventions can be effective [6] and include breathing retraining, anxiety management, activity pacing [7] and cool facial airflow [8].
Severe episodes of acute-on-chronic breathlessness may be caused by a worsening of the underlying disease and/or when distress aggravates the symptom [4]. Acute-on-chronic breathlessness often triggers emergency use of health services [9]. However, one-third of these emergency department (ED) attendees do not need hospital admission and some might be avoidable with adequate community support [9]. Estimates of breathlessness as a primary reason for adult ED presentations range between 2.7% and 9.0% [10–13]. In one UK study, acute-on-chronic breathlessness was a reason for 20% of attendances conveyed by ambulance [9]. The presence and intensity of breathlessness on ED arrival predicts hospital admission [14] and subsequent presentations [15].
For many, the ED is necessary for best care. For others, the ED is less likely to be the optimal place if community-based care is working effectively [16]. Anxiety can play a significant role in people with recurrent acute-on-chronic breathlessness, and for whom targeted, community-based management plans may reduce the need for ED attendances [17].
The American Thoracic Society (ATS) consensus, whilst recognising the evidence gap in the acute setting, recommends a dual approach to acute breathlessness management [18]. Initial management should be given by first responders, using evidence-based, non-pharmacological breathlessness interventions alongside management of any underlying condition. Patients and carers should receive education and training in self-management techniques [18]. For some, an acute worsening of breathlessness can become a “teachable moment” [19] and carers may also learn techniques by observing paramedics [20]. More people with acute-on-chronic breathlessness might thereby be managed safely in the community or, if hospital admission is needed, have their breathlessness reduced more quickly.
We aimed to explore the feasibility and acceptability of conducting a definitive, cluster randomised, controlled trial (cRCT) for people with acute-on-chronic breathlessness due to medical conditions to evaluate the effectiveness and cost-effectiveness of a paramedic-administered, non-pharmacological breathlessness intervention Breathlessness RElief AT HomE (BREATHE).
Material and methods
Details of the planned methods for this mixed-methods feasibility trial are documented elsewhere [21] and summarised here with protocol amendments due to COVID-19.
Study participants
Paramedic-participants willing to undergo training in study measures, processes and the BREATHE intervention (if allocated) were recruited from Yorkshire ambulance stations. Following consent, randomisation and training, paramedics then delivered usual care or BREATHE intervention plus usual care at appropriate call-outs. Usual care was defined by the Joint Royal College Ambulance Liaison Committee (JRCALC) guidelines [22].
Eligible patients were in their usual home environment receiving an emergency response from participating paramedics because of acute-on-chronic breathlessness. They had self-reported cardiorespiratory disease, chronic breathlessness (breathless most days for ≥3 months) and gave retrospective consent for call-out data use at the end of the call-out. Patients needing immediate life-saving intervention in the paramedic's judgement were ineligible. Eligible carers were adults present at call-out to a patient-participant consenting to follow-up.
Study design
We explored the feasibility of a cRCT to evaluate the effectiveness and cost-effectiveness of a paramedic-administered non-pharmacological breathlessness intervention for people with acute-on-chronic breathlessness who have called an ambulance.
Objectives
We addressed the following uncertainties for a definitive trial:
Paramedic-participants’ and patient-participants’ recruitment and attrition rates
Randomisation and consent process: acceptability, possibility within clinical priority time constraints
Intervention: acceptability, adherence and fidelity, implementation issues (trial procedures and clinical practice), safety, contamination
Feasibility of data collection and best primary outcome
Sample size estimation using variability values for candidate primary outcomes
The trial procedures for patient-participants are outlined in figure 1 and table 1.
BREATHE Study flowchart. #: indicates amendments to published protocol, trial procedures adapted due to delivery during COVID-19 pandemic.
Schedule of events for patient-participants and care-participants
Sample size
As a feasibility study, a formal sample size calculation was not required. We aimed to recruit 60 patient-participants over 6 months, 30 per group, to provide sufficient data to answer our research questions [23].
Recruitment, randomisation and consent
Paramedic-participants were recruited, consented and randomised as previously described [21], with an amendment allowing electronic consent. Paramedics were randomly allocated (paramedic being the unit of randomisation) at an intervention:control ratio of 1:1 by the Hull Health Trials Unit (HHTU) using a purpose built, web-based data capture system with integrated randomisation (REDCap cloud). An independent statistician prepared the randomisation schedule with random permuted blocks of size 2–4. All researchers involved in the analysis of the quantitative data were blinded to allocation.
Patient-participants were recruited and consented at call-out, with an amendment due to pandemic restrictions allowing those who consented at call-out for further contact to be phoned to discuss follow-up, gain verbal consent and arrange Day 14 data collection.
Training
All paramedic-participants received 1-h study training on consent and study procedures, with 30-min intervention training if randomised to BREATHE. The first group was trained in-person, with an amendment due to pandemic restrictions allowing online training, and refreshers provided on request.
Data collection
Paramedics accessed REDCap cloud during call-outs via a Toughbook, their standard-issue tablet, and by researchers to input follow-up questionnaire data. A NoMAD (Normalisation Measure Development) survey was completed in REDCap by intervention paramedics. Qualitative data (online interviews and focus groups) were conducted by a researcher (AHu) using a semi-structured topic guide developed by the research team (see supplementary material), recorded and transcribed verbatim. All study-active paramedics were invited to take part in the focus groups. Patients and carers consenting to further contact were invited to take part in an interview. No participants were asked their reason for declining to take part in focus groups or interviews.
Intervention
BREATHE is described in table 2 (for evidence-based references, see protocol paper) [21] and reported in accordance with the template for intervention, description and replication (TIDieR) checklist [24] (supplementary material). Modifications to the intervention were in response to pandemic-related infection control procedures.
BREATHE intervention and usual care
Outcomes and assessments
Candidate primary outcomes were conveyance to hospital (transport of patient from their home to the hospital by ambulance) or change in breathlessness intensity measured at call-out (numerical rating score (NRS) every 2 min). Follow-up data included the 36-item Short-Form Health Survey (SF-36) and the Chronic Respiratory Questionnaire (CRQ). Participants recruited later in a funded extension (due to COVID-19) were only followed-up to 3 months. An additional paramedics’ focus group and a free text survey were conducted to gain further insight about trial experiences.
Analysis
Quantitative data were described using STATA 17 [25]. Intervention fidelity was assessed by component completion rates. Framework analysis was performed for interview, focus group and survey data informed by Normalisation Process Theory [26], managed with NVivo 12 software. Preliminary qualitative findings were discussed, then refined following open discussion with co-authors. This trial is reported consistent with relevant Consolidated Standards of Reporting Trials (CONSORT) statements [27].
Safety
At call-out paramedics were instructed to record any adverse events. A research paramedic accessed clinical records to check for repeat call-outs within 48 h of the index visit.
Ethics approval
The trial was approved by the Yorkshire and Humber-Sheffield Research Ethics Committee (Reference: 19/YH/0314) and institutional ethics committee and registered (ISRCTN80330546) prior to recruitment.
Results
Paramedic recruitment was open between December 2019 and December 2021. Patient–participant recruitment was open for 12 months between February 2020 and June 2021 (includes 5-month COVID-19 pause); follow-up ceased in July 2021. Figure 2 details the recruitment, consent and data collection for paramedics, patient-participants and carer-participants. Quantitative data were collected at call-out for 13 patient-participants (primary end-point) and at follow-up for eight out of 13. Two paramedics completed the NoMAD survey [27]. Qualitative data were collected by interview for six patient-participants and two carer-participants and by two paramedic focus groups (n=7; n=8), and a free text survey.
CONSORT diagram showing participant recruitment and retention throughout the trial. YAS: Yorkshire Ambulance Service.
Recruitment and retention
Paramedic (cluster) recruitment
29 paramedics were recruited; nine (31%) withdrew. Recruitment per cluster varied between zero and three.
Paramedic characteristics
Paramedic characteristics were as follows: male (52%), white (100%) and mean number of years’ experience 5 (range 1–26) years.
Patient and carer recruitment
13 patient-participants were recruited: all agreed to be contacted by a researcher about follow-up and nine (69%) consented to follow-up (one withdrew before data collection). Three carer-participants were recruited for interview. Paramedics stated they saw far fewer of our target group during the pandemic (table 3). The stop-go criterion for recruitment (≤60% target) was not met. The original recruitment period of 6 months was extended to 12 months with a funded extension of the study. Given the ongoing pandemic challenges at the end of the funded extension, the study oversight committees then agreed it was not feasible to pursue any further extension and the study was closed.
Quotes from participants
Participant characteristics
All patients recruited met the eligibility criteria. Patient-participant characteristics were as follows: male (61.5%), mean±sd age 76.4±10.7 years, from the four most deprived deciles of the Index of Multiple Deprivation (100%), lived alone (61.5%) and white (100%). The most common diagnoses were COPD (n=10 out of 13) and heart disease (n=seven out of 13). Characteristics were similar between arms. Carer-participants were adult female family members.
Acceptability of randomisation and training to paramedics
All 29 paramedics approached consented. Withdrawal was balanced across the trial arms (reasons given in figure 2). Randomisation and training (trial processes; intervention) were acceptable to all responding (qualitative data).
Feasibility and acceptability of consent processes
Qualitative data found in-person and electronic consent processes feasible, quick and acceptable to paramedics, and the two-stage consent process was acceptable and feasible to patients.
Intervention: fidelity and adherence
The intervention was delivered with fidelity and no contamination. During the pandemic, the handheld fan was discussed but not demonstrated, substituted by a damp tissue to face and/or opening a window (table 4).
Intervention fidelity and adherence
Intervention: acceptability
Qualitative and NoMAD survey data show acceptability to patients, carers and paramedics.
Intervention: patients’ and carers’ views
Patient-participants found the intervention provided them with useful techniques and resources. However, the intervention may not be acceptable to all patients; one paramedic stated she had seen a patient who engaged poorly with the intervention wishing for immediate hospital transfer (this patient was excluded because they did not give retrospective consent for data use) (see table 3). The intervention was well received by patient-participants.
Two patients did not read the information booklet or leaflet, one patient and carer read and derived benefit from both and another patient and carer read the leaflet and then dealt with two further episodes without calling an ambulance.
Intervention: paramedics’ views
NoMAD responses indicated paramedics saw potential in BREATHE. Qualitative data indicated that BREATHE was useful and easily incorporated into practice. Paramedics valued the intervention, especially improving airflow, resting positions, breathing exercises and distraction to help with anxiety. Components combined easily and helped engagement with patients (table 3). The leaflet was a useful guide for them and for carers and patients for later use. Carers got involved with breathing exercises and reassurance.
All four intervention-arm paramedics would recommend training paramedics in BREATHE to improve their skills since they see many breathless patients and it is simple to learn and to do. They felt that BREATHE would enhance the part they play in community patient care.
Some had incorporated BREATHE into practice and noted that parts of the intervention were helpful with anxious patients in general. One suggested that a GP referral post call-out would be useful for help with breathlessness management long-term.
Safety
There were no adverse events at call-out and no repeat call-outs within 48 h.
Data quality
Data collection at call-out was complete for all items of routinely collected data, except for the second temperature and pulse measurements.
Call-out
Candidate primary outcome measures
Data completion of the potential primary outcome of conveyance was 100% and for the NRS breathlessness intensity score data completion was above 75% for the control group at 6-min intervals, whereas for the intervention arm it was between 20% and 60% complete. NRS intensity scores decreased in both arms (table 5).
Numerical rating scores summary statistics (numerical rating scale of breathlessness intensity 0–10)
NRS score measurement every 6 min, but not 2 min, was acceptable to patient-participants and paramedic-participants, and they found clinical conveyance decisions acceptable. Paramedic-participants were confident in their conveyance clinical decisions. Patients interviewed found it acceptable to remain at home, where this occurred, preferring this to hospital conveyance unless necessary. This may not be the case for all in routine practice: the two (excluded because of lack of retrospective consent) reported via paramedic qualitative data insisted on conveyance.
A similar proportion in each arm were conveyed to hospital (one out of five intervention, two out of eight usual care). Though the sample size was small, our findings suggest that on-scene time for the intervention arm took no longer than controls (intervention mean: 87 min, control mean: 90 min), the intervention being incorporated into the paramedics’ routine.
Follow-up
Data collection was 100% at 14 days, 75% at 30 days and above 50% at 3 or 6 months (table 6). All health service utilisation questionnaires were fully completed. Of the SF-36 questionnaires, 14 out of 19 (74%) had data to calculate the short-form six-dimension (SF-6D) score. CRQ mastery scores could be calculated from all 19 CRQs. All data were collected by phone, taking 30–40 min. The researchers found patients had difficulty with answering the CRQ questions, which were time-consuming.
Follow-up data completion
Implementation issues
From qualitative data, paramedics valued participation and found the intervention (as relevant) useful and acceptable. They were satisfied with intervention and trial procedure training and support. Suggestions for improvement included providing: a scenario to practice applying eligibility criteria; face-to-face and video with online training material; and regular videocalls with participating paramedics for peer support and updates on trial progression. Accessing the study database by Toughbook was problematic for some: inability to log in, poor internet access and time constraints. This led to at least one patient not being recruited into the study (table 3). Suggestions included paper case report forms (CRFs) at call-out with input to the database later, streamlining the online data entry process and database access via smart phone.
Stop-go criteria for recruitment and adherence
Recruitment stop-go criteria were not met. However, the intervention was delivered with fidelity and no contamination, and met the adherence criterion.
Sample size calculation and proposed primary outcome for a definitive trial
Although data completion was good, only 13 patients were recruited. A sample size calculation for a full trial or clarification of the best primary outcome was not possible.
Discussion
A definitive cRCT to evaluate the effectiveness and cost-effectiveness of a paramedic-administered, non-pharmacological breathlessness intervention for people with acute-on-chronic breathlessness due to medical conditions is feasible in terms of data quality, adherence, fidelity and acceptability of the intervention and acceptability of trial processes, but recruitment was not feasible to target during the pandemic. We have valuable information to inform a definitive trial, but we have insufficient data to determine a sample size, nor to identify the most appropriate primary outcome.
Most recruitment occurred under very difficult conditions (for both patients and for ambulance services) at the height of the various waves of the pandemic, with fewer call-outs to Yorkshire Ambulance Service by this particular patient population and increased demand on the service and individual paramedics.
Informing a definitive trial
It would not be possible to recruit to a definitive cRCT if patient call-out for acute-on-chronic breathlessness continued at COVID-19 pandemic rates. However, we demonstrated the acceptability of many study processes including: study and intervention training; randomisation and consent; intervention acceptability, adherence and safety; and patient-reported data collection, which informs our proposed study design adaptations.
The BREATHE intervention was simple to learn and use and acceptable to recruited participants. A future study should note how the intervention is received by patients excluded from analysis due to lack of consent; those not consenting may be those less likely to find BREATHE acceptable. The intervention needs no modification at call-out, but further primary care contact post call-out to promote sustained breathlessness management may be helpful. There were no non-conveyance safety issues and paramedics were confident in their clinical decisions.
Implications for further research
The research question remains important with ongoing distress for patients with acute-on-chronic breathlessness, and pressure on ambulance services and emergency departments; further research is needed to address this problem. Uncertainties remain about the feasibility of a future study.
We propose the following:
Include an embedded pilot to address remaining uncertainties.
Recruit from multiple NHS ambulance services.
Deliver intervention as currently described at call-out but consider triggered follow-up in primary care.
Allow both face-to-face and remote solutions for intervention training delivery.
Reduce the number of patient-reported outcomes, do not include CRQ.
Refine methods of recording data and consent at call-out.
Capture the experience of all otherwise eligible patients, e.g., Confidentiality Advisory Group approval to use call-out data without consent or use a quality improvement paradigm [28].
Given the small clusters (number of participants/paramedic), a cRCT sample size may be prohibitive. Other study designs will be considered, e.g., quasi-experimental and/or RCT using the paramedic-participant first dyad as the unit of randomisation for effectiveness.
The ADePT process [29] will be used to inform a large-scale trial design.
Strengths and limitations
The study was delivered in the NHS by usual care practitioners and in the intended setting. The use of retrospective consent ensured immediate necessary treatment. Another strength was our use of mixed-methods. Qualitative findings helped identify problems and solutions to inform a future trial.
The study had some limitations. The patient/carer sample comprised white British English speakers, and was unrepresentative of the general population. We did not recruit enough paramedics initially, adding to pandemic recruitment challenges and did not meet patient recruitment targets, nor collect sufficient data to meet all objectives. Due to COVID-19 we were unable to use the fan during call-out, which has more supportive evidence than the cold facial wipe. We kept no record of reasons for declining to take part in any aspect of the study, which may give an incomplete picture of the intervention (as well as study participation) acceptability; Suggested future study designs above would help address this.
Conclusion
Patient recruitment to target was not feasible during the COVID-19 pandemic. Training and intervention were acceptable and delivered with fidelity. Results include valuable information on recruitment, consent, attrition and data collection that will inform adaptations for the design and delivery of a definitive trial.
Supplementary material
Supplementary Material
Please note: supplementary material is not edited by the Editorial Office, and is uploaded as it has been supplied by the author.
TIDieR checklist to describe the BREATHE intervention 00257-2022.SUPPLEMENT
Semi-structured interview (patient and carer if present) 00257-2022.BREATHEInterviewTopicGuideFollow-upPatientandCarer
Semi-structured interview/focus group with paramedics 00257-2022.BREATHEInterviewTopicGuideParamedic
Acknowledgements
We wish to acknowledge the contributions of Jane Shewan, Fiona Bell, Richard Pilbery, Elisha Miller and the participating paramedics from Yorkshire Ambulance Service and Pat Hatfield (PPI representative) for her input as a co-applicant and member of the TMG. Finally, we thank Anne English for her assistance in delivery of the paramedic training sessions. We would like to thank all of the members of the trial steering committee and the stakeholder group and we are grateful for the support of Asthma and Lung UK throughout this study.
Footnotes
Provenance: Submitted article, peer reviewed.
This study is registered at https://www.isrctn.com with identifier number ISRCTN80330546. All of the individual participant data collected during the trial will be shared after deidentification. The study protocol paper has been published. A fully anonymised dataset will be made available to authorised researchers upon request to the corresponding author, when a data sharing agreement is in place.
Author contributions: A. Hutchinson, V. Allgar, S. Hart, A. Hodge, M.J. Johnson, S. Mason, J. Reeve, S. Griffin and F. Swan were co-applicants on the grant application. M. Northgraves, J. Cohen, V. Allgar, D.C. Currow, S. Hart, K. Hird, A. Hodge, M.J. Johnson, S. Mason, F. Swan, J. Reeve, S. Griffin and A. Hutchinson assisted in development of the protocol and implementation of the study. A. Hutchinson, M. Northgraves and M.J. Johnson drafted the manuscript. All authors read and approved the final manuscript.
Conflict of interest: A. Hutchinson reports grants from NIHR during the conduct of the study.
Conflict of interest: V. Allgar reports grants from NIHR during the conduct of the study.
Conflict of interest: J. Cohen reports grants from NIHR during the conduct of the study.
Conflict of interest: D.C. Currow reports the following. Helsinn Pharmaceuticals: advisory board member; Mayne Pharma: paid consultant and received payment for intellectual property.
Conflict of interest: S. Griffin reports grants from NIHR during the conduct of the study.
Conflict of interest: S. Hart reports grants from NIHR during the conduct of the study; and personal fees from Trevi Therapeutics, and personal fees and nonfinancial support from Chiesi and Boehringer Ingelheim, outside the submitted work. He is an associate editor of this journal.
Conflict of interest: K. Hird reports grants from NIHR, during the conduct of the study.
Conflict of interest: A. Hodge reports grants from NIHR during the conduct of the study.
Conflict of interest: S. Mason reports grants from NIHR during the conduct of the study.
Conflict of interest: M. Northgraves reports grants from NIHR during the conduct of the study.
Conflict of interest: J. Reeve reports grants from NIHR outside the submitted work.
Conflict of interest: F. Swan reports grants from NIHR during the conduct of the study.
Conflict of interest: M.J. Johnson reports grants from NIHR during the conduct of the study.
Support statement: This paper presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0817-20009). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. Funding information for this article has been deposited with the Crossref Funder Registry.
- Received May 27, 2022.
- Accepted August 11, 2022.
- Copyright ©The authors 2022
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References
