SINFONIA study protocol: a phase II/III randomised controlled trial examining benefits of guided online group singing in people with chronic obstructive pulmonary disease and interstitial lung disease and their carers

Study design and setting

A parallel, double-arm, randomised, blinded-analysis, mixed-methods phase II/III trial of guided, online group singing will be conducted over 24 months. Adults with COPD or ILD and their adult carers (optional) will be eligible to participate. Methods reported in this paper are reflective of protocol version 1.2, 30th September 2021. Participants will be recruited from tertiary respiratory care clinics based at the Alfred Hospital, Austin Health, Royal Melbourne Hospital, and St Vincent’s Hospital in Melbourne, Australia. People who are not cared for by these health services may also be referred to the study by their primary care provider (e.g., general practitioner) or by self-referral. An advertising poster with eligibility criteria and contact details will be circulated amongst specialist and community pulmonary care services to enable referral. All referred patients will be reviewed by an investigator at a study site to confirm eligbility. Ethics approval for the study was obtained from the St Vincent’ Hospital Melbourne Human Research and Ethics Committee (LRR 237/21).

Participants

Adults with confirmed COPD or ILD, on stable treatment for at least four weeks at time of recruitment, with a modified Medical Research Council (mMRC) dyspnoea score of two or greater, who are capable and willing to give consent, are eligible to participate. Diagnosis of COPD or ILD must be confirmed by lung function testing within the past two years or computed tomography (CT) chest scan within the past five years. Stable treatment is defined as no new or altered doses of cardiorespiratory medications (including antibiotics and oral steroids) as assessed by the study site clinician, and no hospital admissions for exacerbation of their underlying disease within the past four weeks. Participants who are actively enrolled in a PR program are excluded from participation; however past completion is permitted. No other exclusion criteria exist. A nominated carer (aged 18 years or over) per participant may optionally be enrolled. Referral of participants who are not patients of the study site clinics is permitted. Informed written consent will be obtained by an appropriately trained member of the study team.

Intervention and data collection

Participants and their carers (optional) will be enrolled for a period of 12-weeks (Fig. 1). After signing consent, participants will be randomised 1:1 to intervention or control arms with the randomisation sequence developed by the trial statistician using permuted block design (Stata statistical package [39]), and stratified by disease type (ILD vs COPD). Allocation sequence will not be visible to personnel involved in study recruitment. Participants randomised to the intervention arm will attend one 90-minute, guided, online, group singing session per week for 12 weeks. Enrollment will be on a rolling basis with a maximum of 12 patient participants and 12 carers, with up to two groups running concurrently.

Fig. 1figure 1

The online program will be delivered via a teleconferencing platform such as Zoom. Online, group singing sessions will be conducted by a senior music therapist with expertise in singing and delivering an individualised, enjoyable singing repertoire suitable for patients with ALD (Table 1). Singing activities will focus on breathing control and will include a warm-up. Participants will be encouraged to suggest songs. During the 90 minute class, some time will be dedicated to socialisation and group connection. The exact content and structure of the online group singing sessions will be refined during phase II.

Table 1 SINFONIA music therapy session plan

In addition to attending weekly, guided, online, group singing sessions, participants will be given music CDs, with repertoire and exercises from the guided group singing sessions, to utilise regularly at home. Control arm participants will receive standard care for 12 weeks, with the option to enroll in 12 weeks of guided, online, group singing at the completion of the study period (no data will be collected during this optional period). Participants and their carers will be contacted at 4-week intervals to collect study assessments. The intervention may be discontinued at any time at the participants request or if the site principal investigator deems a participant too unwell to continue. Data will be collected and stored on a REDcap server which is at least as secure as the source. Data will be accessible only by authorised members of the study team and will be stored in accordance with relevant local policies and guidelines to ensure confidentiality.

Aims and outcomes

Phase II of the trial aims to determine the feasibility and acceptability of guided, online group singing and will collect preliminary data on effectiveness. The primary outcome of feasibility and acceptability will be assessed by the number of participants (and optional carers) that can be recruited, enrolled, and who complete the study within a six-month period (Table 2). Completion will be defined as attendance at a minimum of eight out of 12 sessions over a 12-week period for the intervention arm and completion of the 12-week assessment for the control arm.

Table 2 Phase II and III primary and secondary outcomes

Phase III aims to determine whether guided, online group singing has an effect on quality of life with the primary outcome being between arm difference in quality of life (36-item Short Form Survey (SF-36)) measured at 12 weeks (Table 2) [40]. Secondary outcomes measured using between arm differences at the 12-week timepoint include effects on: anxiety and depression (Hospital Anxiety and Depression Scale (HADS)) [41], breathlessness (Dyspnoea-12) [42], breathlessness mastery (Chronic Respiratory Disease Questionnaire—Self Administered Standardised mastery subdomain (CRQ-SAS)) [43, 44], exercise tolerance (6 Minute Walk Test (6MWT)) [45], loneliness (University of California Los Angeles Loneliness Scale version 3 Short Form (UCLA-3)) [46], healthcare utilisation (self-report), carer quality of life (SF-36, optional), patient and carer perceptions of group singing (thematic analysis of semi-structured interviews) [47], and social dynamics and interactions (ethnographic observation) [48]. We hypothesise that 12 weeks of online, guided group singing will improve health-related quality of life relative to baseline compared to usual care.

Online, group singing sessions will be attended and/or recorded and reviewed by a member of the study team to conduct ethnographic analyses on the interactions between patients, carers, and singing instructors. Additionally, a purposive sample of up to 15 participants from ILD, COPD, and carer groups will be recruited for semi-structured interviews before, during, and after the intervention period to investigate perceptions of the guided, online, group singing intervention. A related ethics approval has been obtained to allow interviews with eligible participants who elect not to continue with the main study (St Vincents Hospital Melbourne HREC, LRR 111.21).

Sample size

No formal power calculation was performed for phase II. Participant numbers will be assessed at 6-months to determine feasibility of phase III. For phase III, given a minimally clinically relevant difference in SF-36 of 10 points (SD 16) [31, 35] and assuming 80% power and 5% significance level, at least 42 participants per arm are required. To account for 40% attrition rate, at least 140 participants will be recruited. Due to the rolling nature of the singing groups, the clustering effect is assumed to be minimal, therefore no adjustment for clustering has been performed.

Treatment allocation

Treatment allocation will be in 1:1 ratio. A randomisation sequence will be developed by the trial statistician who is not involved in recruitment using permuted block design using Stata software [39], stratified by disease type (COPD vs ILD). No trial investigators or personnel will have access to the allocation sequence.

Safety and adverse event reporting

At each study follow up timepoint, the participants are encouraged to mention any problems since the last visit. For all randomised participants all adverse events, irrespective of causality, will be assessed and recorded as per Improving Palliative, Aged and Chronic Care through Clinical Research and Translation Trials Coordination Centre Standard Operating Procedure 5.17 Adverse Event Reporting [49]. The time period includes the time from randomisation, monthly during the intervention period and at the follow-up review. For patients who meet the eligibility criteria and then do not proceed to randomisation, any adverse events detected during that window of time, should also be reported. If an adverse event is the reason that a person does not proceed to randomisation, this should be recorded. All adverse events will be reported in summary to the reviewing HREC and site RGO and will be followed-up until: resolution; condition stabilises; event can be explained; participant is lost to follow-up; or death.

Statistical analyses

Phase II feasibility and acceptability outcomes will be analysed descriptively. Outcomes from phase II will inform the delivery of phase III. Phase III primary and secondary outcomes will be analysed on intention-to-treat basis using mixed effect linear regression. Participants will be entered as random coefficients, while time, treatment arm and an interaction between them will be entered as fixed terms. Residuals will be visually inspected and if the model is of poor fit, the outcome will be transformed using natural logarithms. The primary outcome will be expressed as the difference in SF-36 at 12 weeks with 95% confidence intervals. If the model remains of poor fit despite the outcome transformation, then mixed effect ordinal logistic model will be used and results will be expressed as odds ratios with 95% confidence intervals. Additional per protocol analysis will be performed using a subgroup of participants who have completed the last visit and have completed at least 8 sessions over 12 weeks.

Multiple exploratory subgroup analyses will be performed, including: sex (female vs male), age group (60 years, 60–70 years, or > 70 years), disease severity (mild-moderate vs severe), disease type (COPD vs ILD), prior psychological disease (present vs absent), breathlessness (mMRC of 2 vs 3 vs 4), and previous pulmonary rehabilitation (yes vs no). Subgroup analysis will be performed by including an interaction term between subgroup and treatment arm in the initial model. Additional analysis will involve the associations between change in the outcome and compliance to intervention and presence of carer in group sessions. These will be performed using linear regression. Outcomes are collected at multiple time-points throughout the study to allow for better missing data imputation, which will be performed within the mixed effects model (using maximum likelihood estimation).

Semi-structured interviewing will continue until sufficient information power is reached [50]. Given the narrow scope of the qualitative analyses, it is anticipated that sufficient information will be attained with a maximum of 15 COPD patients, 15 ILD patients and 15 carers. Each interview will be transcribed verbatim and thematically analysed for perceived patient and carer preferences, barriers, and opportunities based on the approach described by Braun and Clarke [47]. A purposive selection of session recordings will be analysed for patient experiences, actions, behaviours, and responses based on the approach described by Goodson and Vassar [48]. These qualitative outcomes will supplement the quantitative primary and secondary outcomes from phase III.

Reporting results

This protocol paper has been prepared in accordance with Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines [51, 52]. All results will be reported according to the Consolidated Standards of Reporting Trials (CONSORT) statement for reporting randomised trials [53]. A participant flow diagram will include baseline characteristics, distribution of participants between arms, and number of participants with missing data. Baseline characteristics will be presented by arm using median (with interquartile range) for non-parametric data, or mean (with standard deviation) for normally distributed continuous variables; and as frequencies (percentages) for categorical variables. There will be no adjustment for multiple secondary outcomes, however, the results of secondary outcomes will be interpreted in light of multiple comparisons and focus will be given to their clinical significance.

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