ENO Breathe vs Usual Care in COVID-19 Recovery
Condition: COVID-19 Recovery
MeSH terms: COVID-19
Study type: Interventional

Summary: 
      A randomised clinical trial to assess the impact of an online singing, breathing and
      wellbeing programme (ENO Breathe) developed specifically for people recovering from COVID-19.
    

Detailed description: 
      BACKGROUND:

      ENO Breathe is a breathing and wellbeing programme developed specifically for people
      recovering from COVID-19, who are still suffering from breathlessness and associated anxiety.
      Delivered by ENO in collaboration with Imperial College Healthcare teams entirely online, the
      programme focuses on breathing re-training through singing. Initial evaluation of the project
      suggested health improvements related to participation, however, a properly conducted
      efficacy study is needed.

      DESIGN: An assessor blind, parallel group, randomised controlled trial, to assess the effects
      of ENO Breathe compared to usual care on health status. The study will also evaluate the
      impact on respiratory symptoms, anxiety, depression, and breathlessness perception to
      investigate the mechanisms involved.

      RESEARCH QUESION AND OUTCOME MEASURES:

      The primary outcome will be change in health status, assessed using the RAND-36 tool (RAND
      SF-36), comparing ENO Breathe and Usual Care arms.

      Additional endpoints will be: the COPD assessment test score (CAT), 0-100 Visual Analogue
      Scales (VAS) for breathlessness (at rest, walking around the house, climbing stairs, and
      running), Dyspnoea-12, anxiety (GAD-7), and depression (PHQ-9).

      Assessments: The outcomes outlined above will be recorded at baseline prior to randomisation,
      and then repeated after 6 weeks.

      POPULATION: Adult patients recovering from COVID-19 will be recruited from specialist
      COVID-19 clinics, where participants will have been fully assessed and investigated by
      referring healthcare professionals. Participants in the active arm will attend once weekly
      ENO online workshop sessions for 6 weeks, and have access to bespoke online digital
      resources, designed to support participants between sessions. The comparison arm will receive
      usual care. Randomization will be 1:1.

      SAMPLE SIZE Sample size: Based on pilot data in people with COPD, where the standard
      deviation (SD) for change in SF-36 was 15 points, to identify a clinically relevant 10 point
      difference in SF-36 responses at a 0.05 level of significance with a 90% power would require
      48 patients in each treatment arm. Allowing for 20% dropout, we will therefore recruit 120
      patients.

      Primary analysis will be on an intention to treat basis. Change in parameters will be
      assessed comparing ENO Breathe and Usual Care, using Generalised Linear Models to estimate
      treatment effects. In order to better understand changes in the RAND-36 "anchor measure", the
      investigator will relate this to changes in measures of anxiety, depression, breathlessness,
      and other respiratory symptoms.

      An additional responder analysis will compare the proportion in each treatment arm achieving
      a clinically important (10%) improvement in RAND-36 scores.

      Update 21 JUNE 2021

      To calculate the sample size, pilot data from a singing-based intervention in COPD,
      (considered the most relevant data available at study inception) was used, as outlined above,
      where the researchers aimed to recruit 120 patients. Data subsequently became available from
      ENO Breathe participants that rook part in the program prior to the research study, in which
      the SD was 8 for change in SF-36 scores. We have also decided using an MCID of 5 for the
      SF-36 is more appropriate, as this is not specific to a particular medical condition. As
      such, a total sample of 108 participants is required, using 1 to 1 study arm allocation.
      Allowing for 30% dropout, which is more appropriate, 158 participants will be recruited.
      Additionally, as a higher than expected number of participants were considered, study
      withdrawals due to be unable to attend the session times they were allocated, or despite
      meeting inclusion criteria, 1-to-1 meeting with the session leaders highlighted issues
      related excessive fatigue precipitated by exertion, so were not deemed appropriate at that
      point in time. As such, the researchers will also conduct a modified intention to treat
      analysis including all participants who were randomised and were deemed appropriate to
      participate following their 1-to-1. This consideration had not been included in the original
      exclusion criteria, due to limited awareness of its relevance at that time. These changes
      have been made, and here documented, before any baseline data has been sent to the analysis
      team, and before any follow up data has been collected.
    

Intervention name(s): ENO Breathe group
Intervention type(s): Other
Intervention description(s): Six weekly group online workshop sessions, led by an ENO vocal specialist. Workshops will encourage participants to take part in exercises and activities especially designed to support breathing control, providing tools for self-management of breath and anxiety. They will also have access to bespoke online digital resources, designed to support participants between sessions. These will include exercises, song sheets and audio and video materials, especially recorded by the ENO for participants on the programme.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary purpose: Treatment