STRIVE pilot trial: a protocol for a multicentre pragmatic internal pilot randomised controlled trial of Structured TRaining to Improve fitness in a Virtual Environment (STRIVE) before surgery

Abstract

Introduction

Home-based, virtually-supported care models may represent the most efficient and scalable approach to delivering prehabilitation services. However, virtual approaches to prehabilitation are understudied. This manuscript describes the protocol for an internal pilot randomised controlled trial of a virtually-delivered, multimodal prehabilitation intervention.

Methods and analysis

We will conduct a pragmatic, individual patient, internal pilot randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals. Participants will be partially blinded; clinicians and outcome assessors will be fully blinded. The intervention consists of 3–12 weeks of a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. The primary feasibility outcomes and their progression targets are (1) monthly recruitment of>6 participants at each centre, (2) intervention adherence of>75%, (3) retention of>90% of participants at the patient-reported primary outcome point of 30-days after surgery and (4) elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial. A sample size of 144 participants will be adequate to estimate recruitment, adherence and retention rates with acceptable precision. All participants will be followed to either death or up to 1 year. As an internal pilot, if no substantive changes to the trial or intervention design are required, pilot participant outcome data will migrate, unanalysed by allocation, to the future full-scale trial.

Ethics and dissemination

Ethical approval has been granted by Clinical Trials Ontario (Project ID: 4479) and our ethics review board (Protocol Approval #20230399–01T). Results will be disseminated through presentations at scientific conferences, peer-reviewed publications, partner organisations and engagement of social and traditional media.

Trial registration number

ClinicalTrials.gov identifier NCT06042491. Protocol, V.1.2, dated 6 June 2024.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• Estimating the feasibility of a protocol to evaluate a home-based, multimodal, virtually supported prehabilitation programme using patient-centred outcomes.

• Will inform the full-scale trial’s ability to guide future implementation of prehabilitation in clinical practice.

• Assessment of barriers and facilitators will help address logistical challenges to improve the full-scale trial.

• Complex intervention, possible risk of intervention contamination.

Introduction

Globally, more than 300 million people have surgery each year, mostly on a planned (also called elective) basis.¹ People presenting for surgery face a substantial risk of postoperative adverse events. 15–30% of patients suffer a serious medical or surgical complication after surgery2,4 and one in five develop a new patient-reported disability associated with a loss of independence in day-to-day life.^{5 6} As more people present for surgery, the average risk profile of surgical populations is rising.7,9 An increasing number of surgical patients are older and live with comorbidity.^{7 10} This means that strategies to improve patient outcomes and reduce resource utilisation are urgently needed.

Patients, the public, clinicians and policymakers have identified prehabilitation as a top 10 priority for perioperative research.^{11 12} As surgery induces physiological stress similar to that caused by sustained moderate-to-vigorous physical activity,¹³ there is strong face validity underlying the hypothesis that optimising preoperative nutrition and physical function could reduce postoperative adverse events. However, because almost all prehabilitation trials to date are single centre and have moderate to high risk of bias, evidence of prehabilitation’s efficacy in improving outcomes, while consistent and promising, is low-certainty.¹⁴

Systematic reviews highlight that rigorous, multicentre prehabilitation trials are required and provide insights into what types of prehabilitation interventions are most likely to be effective. In a recent network and component network meta-analysis of 186 randomised trials involving more than 15 000 patients, isolated exercise and nutritional prehabilitation interventions as well as multicomponent interventions including exercise had the highest probability of efficacy and demonstrated clinically meaningful improvements in complication rates (OR<0.8), length of stay (≥1-day reduction) and functional recovery (>20-metre improvement on the 6-minute walk test).¹⁵ This suggests that in addition to multicentre trials oriented to demonstrate the effectiveness of prehabilitation, research informing the effective clinical implementation of prehabilitation is also required.

A multicentre pragmatic trial of prehabilitation which simulates the real-world application of prehabilitation in usual care settings addresses two key knowledge gaps in the translation of prehabilitation evidence into clinical care. Such a trial could concurrently estimate whether participation in an evidence-based multimodal prehabilitation intervention leads to clinically meaningful improvements in outcomes while informing the feasible implementation of prehabilitation in usual care settings. Pragmatic trials, however, have unique considerations that should be tested prior to large-scale evaluation. Chan and colleagues have recommended 10 key elements to consider prior to large-scale evaluation in a pragmatic trial.¹⁶ In particular, whether adequate recruitment, adherence and outcome follow-up can be achieved in the setting of pragmatic prehabilitation evaluation remains uncertain.

Given the need to pragmatically evaluate prehabilitation’s effectiveness in usual care settings while collecting key information to inform future widespread implementation, we will conduct an internal pilot, pragmatic, multicentre randomised controlled trial comparing home-based, virtually supported, multimodal prehabilitation to standard care in adults having inpatient, elective thoracic, abdominal, pelvic and vascular surgery to help determine the feasibility of a full-scale pragmatic trial powered to demonstrate a clinically meaningful difference in patient-reported disability scores 30 days after surgery.

Methods and analysis

Study design and setting

The Structured TRaining to Improve fitness in a Virtual Environment (STRIVE) pilot trial is an internal pilot individual patient randomised controlled trial of home-based, virtually supported, multimodal prehabilitation compared with standard perioperative care in adults undergoing elective, inpatient elective thoracic, abdominal, pelvic and vascular surgery at five Canadian hospitals (The Ottawa Hospital—Civic Campus, The Ottawa Hospital—General Campus, Sunnybrook Hospital, St Michael’s Hospital and Royal Columbian Hospital). The Ottawa Hospital Research Institute will serve as the coordinating centre. This protocol is reported in keeping with the Standard Protocol Items: Recommendations for Intervention Trials guidelines.¹⁷ Research ethics board (REB) approval has been granted from Clinical Trials Ontario (CTO, Project ID: 4479), The Ottawa Health Sciences Network—REB (Protocol # 20230399–01T) and will be granted from all participating centres prior to the commencement of recruitment. Eligibility criteria are outlined in box 1. This study has a start date of 30 January 2024 and an end date of 30 September 2025.

Box 1. Inclusion and exclusion criteria for the STRIVE pilot trial.

Inclusion criteria

• Age>18 years.

• Scheduled or on the pathway for inpatient elective abdominal, thoracic, pelvic, head-and-neck or vascular surgery.

• Expected surgery date between 3 and 12 weeks from enrolment.

• Valid provincial health insurance number.

• Access to internet-enabled device.

• Email address.

Exclusion criteria

• Inability to read and communicate in English.

• Cognitive impairment that prevents independent informed consent.

• No telephone/cell phone.

• Cardiac, neurological or orthopaedic procedure.

• Surgery without curative intent (palliative surgery).

• Patient not interested in participating in the context of their Telephone Assessment of Physical Activity (TAPA) score.*

*The TAPA is a brief telephone questionnaire to assess physical activity in older adults that includes two components: (1) aerobic and (2) strength and flexibility.⁶⁸ While there is no exclusion based on the score, the score will allow patients the opportunity to make the decision to participate or not based on their score if they score>5 as the STRIVE intervention might be less ‘rigorous’ than the activity they are already doing.

• Any of the following cardiovascular conditions:

  • Severe valvular heart disease that limits a patient’s ability to ambulate on level ground or is associated with syncope or dyspnoea.

  • Severe cardiac dysrhythmias that limits a patient’s ability to ambulate on level ground or is associated with syncope or dyspnoea.

  • Recent myocardial infarction (within the 6 weeks prior to enrolment based on the Heart and Stroke Foundation’s HeartWalk Programme).

Items from the WHO Trial Registration Data Set are reported in table 1.

Table 1. All items from the WHO trial registration data set.

Data category	Information
Primary registry and trial identifying number	ClinicalTrials.gov NCT06042491
Date of registration in primary registry	18 September 2023
Secondary identifying numbers	Not applicable
Source(s) of monetary or material support	The Canadian Institutes of Health Research, The Ottawa Hospital Medical Organization University of Ottawa Department of Anesthesiology and Pain Medicine
Primary sponsor	The Ottawa Hospital Research Institute
Secondary sponsor	Investigator-led, Dr Daniel I McIsaac
Contact for public queries	DIM, dmcisaac@toh.ca
Contact for scientific queries	DIM, dmcisaac@toh.ca
Public title	Helping people to prehabilitate at home before surgery with virtual support in a real-life setting
Scientific title	The STRIVE Pilot Trial: a Pragmatic Internal Pilot Multicenter Randomized Trial of Structured TRaining to Improve Fitness in a Virtual Environment (STRIVE) Before Surgery
Countries of recruitment	Canada
Health condition(s) or problem(s) studied	Major surgery, adults
Intervention(s)	Virtually-supported prehabilitation
Key inclusion and exclusion criteria	Ages eligible for study: ≥18 yearsSexes eligible for study: bothAccepts health volunteers: no
	Inclusion criteria: adult patient (≥18 years), inpatient elective surgery date between 3 and 12 weeks from enrolment, internet-enabled device and email address
	Exclusion criteria: unable to communicate in English, unreachable by telephone, major cardiac risk factors, cardiac, neurological or orthopaedic procedures, scheduled to undergo surgery in fewer than 3 weeks from randomisation
Study type	Interventional
	Allocation: randomised intervention model. Parallel assignment masking: double blind (investigator and outcome assessors)
	Primary purpose: prevention
Date of first enrolment	30 January 2024
Target sample size	144
Recruitment status	Recruiting
Primary outcome(s)	Feasibility

Patient and public involvement

The STRIVE pilot trial was designed using integrated knowledge translation methodology through partnership with patients, clinicians, researchers and health system leaders from elicitation of the research question and continuing throughout the research process.¹⁸ Partnership includes patient representation on the trial’s executive committee (GK).¹⁹ Participant experience with the intervention will be measured quantitatively and qualitatively. Study results will be disseminated to participants and partners through traditional and social media as well as using newsletters and team meetings.

Intervention

Our intervention is a home-based, multimodal (exercise, nutrition and psychosocial support) prehabilitation programme supported through an online platform. Because surgical wait times are inconsistent, the programme is performed for a variable duration of 3–12 weeks.²⁰ The exercise component is based on programming with demonstrated efficacy in improving postoperative physical recovery.^{21 22} The nutrition component is informed by best-practice recommendations for preoperative nutrition.23,25 To date, more than 500 patients have been allocated to versions of this programme in mostly explanatory randomised trials²⁶ with consistent benefit demonstrated in adherent participants and in some intention to treat analyses.^{21 22 27 28} The programme has been further refined and enhanced for the STRIVE pilot trial based on qualitative participant feedback, direct patient–partner input^{29 30} and insights from recent knowledge synthesis.¹⁵ Patients report that similar programmes are easy to follow, enjoyable, suited to individual needs and that lack of exercise experience is not a barrier to participation.²⁹

Each intervention participant will be provided a unique login to the online prehabilitation platform which is accessible via computer, tablet or smartphone. Participants will be provided personalised teaching on the safe performance of prescribed exercises via a phone or video call with a prehab coach and prerecorded videos available on the online platform. Programme materials (pedometer, resistance bands, protein supplementation) will be couriered to the participant. Each participant will then be contacted weekly by a dedicated coach. Participants can contact their coach at any time with questions or concerns. Through the online platform, they will access their personalised exercise programme, group exercise sessions, breathing exercises and nutrition guide. Participants will be provided with a paper logbook to document the completion of prescribed exercises, step counts and intake of protein supplements.

Exercise

The exercise component includes: (1) strength training; (2) aerobic exercise; (3) flexibility; and (4) respiratory training using individual, self-directed sessions and instructor-led group sessions, performed>3 times per week. The form of each exercise is personalised based on the individual’s level of function and in consideration of physical limitations.

Strength training

One set of 10 repetitions of each exercise: (1) push-ups (modified to the individual’s level of function as incline push-ups or knee push-ups); (2) row (elastic resistance band); (3) chest press (elastic resistance band); (4) deltoid lift (elastic resistance band); (5) bicep curls (elastic resistance band); (6) triceps extensions (elastic resistance band); (7) quadriceps; (8) hamstrings; (9) calf raises; (10) abdominal.

Aerobic exercise

Participants are asked to walk or jog for 20 min at moderate intensity. After the first week, the individual’s average daily step count is used to recommend a 10% increase in daily step count each week. A 10% increase in steps per week is considered to be a safe, meaningful and achievable method to personalise activity goals.³¹ For participants who cannot walk or jog (eg, those with musculoskeletal injuries), aerobics can be completed using alternate approaches (eg, swimming, cycling).

Flexibility

Quadriceps, chest, hamstrings, biceps, calves and triceps stretches; each stretch held for 20–30 seconds × two repetitions.

Respiratory training

During their prehab programme, participants will be encouraged to watch inspiratory muscle training videos that direct participants in performing diaphragmatic breathing and coughing/huffing.³² They will also be provided with an instruction booklet to take to hospital with them. Participants will be encouraged to do the breathing exercises daily during the final 2 weeks leading up to surgery. Participants will be asked and reminded to do the breathing exercises hourly on waking from anaesthetic (during waking hours) until the first ambulation. If the participant becomes non-ambulatory, they will be asked to continue the breathing exercises every hour until they are ambulatory again or until discharge.

Group sessions

Optional group sessions will be offered at two times daily via Zoom for Healthcare to facilitate alignment with participants’ schedules. These live sessions, led by a trained kinesiologist, will focus on exercise and breathing sessions.

Nutrition

The nutrition component includes: (1) protein supplementation; and (2) nutritional advice to support healthy eating. Preoperative guidelines recommend malnutrition screening and protein intake of>1.5 g/kg/day.23,2533 To help meet appropriate targets, the nutrition intervention is personalised using The Scored Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF), a validated tool.³⁴ Participants will be sent a whey protein supplement (or plant-based in the case of dairy allergies) according to their PG-SGA SF score: (0–3)=well nourished: 25 g/day (one scoop) when exercising (minimum of three times a week); (4–8) moderately malnourished or suspected malnutrition: 25 g/day (one scoop), 7 days a week, regardless of exercise; (or>9) severely malnourished: 50 g/day (two scoops), 7 days a week, regardless of exercise. The supplement allows participants to achieve or exceed their daily protein target. To support adherence and diversity in participant preferences, the online platform will provide several recipes with ideas for including protein in their diet. The online platform will also host cooking tips and recipes for healthy snacks and meals.

Psychosocial support

The psychosocial support component aims to optimise adherence which is a key mediator of efficacy for exercise and nutrition interventions.³⁵ Our approach is based on behavioural activation³⁶ which is a time-limited, evidence-based approach to increase engagement in healthy behaviours that can be virtually and remotely provided by lay coaches.³⁷ Therefore, all study coaches will receive training in and adhere to principles of behavioural activation in interacting with participants.

Control condition

To support participant blinding, improve enrolment and reflect usual care, widely available physical activity (WHO Recommendations for Physical Activity) and healthy eating (Canada’s Food Guide) documents will be provided as handouts to control participants (without active or online support). The partially blinded control condition is informed by discussion with patient and knowledge user partners. Surgeons partners report routinely advising patients to be more active and improve nutrition before surgery, although support is not provided. Patient partners report that they would be less likely to enrol in a trial if they do not receive any prehabilitation materials intervention. This approach should also reduce performance bias as lack of blinding is a key source of bias in prehabilitation trials.^{14 15}

Preoperative, in-hospital and postoperative care

All other aspects of perioperative management will be at the discretion of treating clinicians. There will be no standardisation of intraoperative anaesthesia or surgical care and participation in perioperative care processes such as enhanced recovery after surgery programmes will be dictated by local practice.

Outcomes

All participants will be followed up to 1 year after surgery or death, whichever occurs first. Clinical outcomes reflect the principles of pragmatic trial design as they are patient-important and other than the primary, validly ascertained from routinely collected data.³⁸ Feasibility outcomes reflect key considerations for the successful completion of this pragmatic trial.¹⁶

Primary feasibility outcomes and progression targets

(A) Monthly recruitment of>6 participants per centre will allow the larger trial to meet estimated recruitment requirements in 12 months. (B) Intervention adherence>75% is likely required to meaningfully benefit from prehabilitation: (1) a value consistent with per protocol adherence definitions in explanatory trials,^{15 27 28} (2) represents a threshold above which participants have achieved greater than minimally important improvements in functional outcomes and^{21 27 28} (3) is consistent with patients’ perceptions of adequate adherence. We will calculate adherence as the proportion of intervention participants completing>75% of prescribed exercise and nutrition tasks in the 3 weeks before surgery. (C) Retention of>90% of participants at the patient-reported primary outcome point of 30 days after surgery represents retention better than that typically seen in explanatory trials and should minimise attrition bias in the full-scale trial’s primary outcome data. (D) Elicitation of patient, clinician and researcher-identified barriers to our pragmatic trial using the Theoretical Domains Framework.^{39 40}

Primary effectiveness outcome (full trial)

Patient-reported disability 30 days after surgery using the WHO Disability Assessment Schedule V.2.0 (WHODAS), a patient-reported disability scale that assesses limitations in six major life domains (ie, cognition, mobility, self-care, social interaction, life activities, participation in society).^{41 42} The WHODAS is valid in surgical populations⁵ (and other acute and chronic conditions),43,49 is identified by surgical patients as a high-priority outcome^{6 50} and is a core patient-centred outcome in perioperative medicine.⁵¹ Each questionnaire item is scored on a Likert scale ranging from 0 to 4. The sum of the responses is the WHODAS disability score (range: 0–48) which is expressed as a percentage of the maximum possible score. People that die prior to follow-up are assigned a score of 100% (completely disabled). A 5% change in disability represents a minimally important difference in surgical patients.⁵² Surgical patients report good to excellent clinical acceptability⁵ and in extensive psychometric evaluation it had high test–retest reliability, internal consistency, concurrent validity and conformity to Rasch scaling properties.⁴¹ The WHODAS V.2.0 is thus a feasible, valid and reliable patient-reported instrument to measure disability.

Secondary routinely collected outcomes

We will collect secondary outcomes via phone or registry linkage (for patients enrolled at centres that can achieve linkage to routinely collected health data). Patient-centred: Health-related quality of life using the EuroQoL 5-domain, 5 level tool (EQ-5D-5L)⁵³; a count of days at home in the 30 days after surgery which is a validated patient-centred⁵⁴ outcome that can be ascertained from routinely collected data.^{55 56} Survival: All-cause deaths and survival time in the 30 days and year after surgery will be captured from vital statistics. Length of stay: Days from surgical admission to discharge. Postoperative complications: A validated set of in-hospital patient safety indicators will be captured from the index hospitalisation record.^{57 58} Intensive care unit (ICU) admission: ICU admission and length of stay are accurately captured by administrative data.⁵⁹ Non-home discharge: Discharge from the index hospitalisation via transfer to a non-home location or death. Readmission: Time to first and count of any acute hospitalisation in the 30 days after surgery. Emergency department visits: Time to first and count of any emergency department visits within 30-days after surgery. Health system costs: A validated patient-level costing algorithm will be used to capture all health system costs accrued within 30 days and 1 year after surgery.⁶⁰

Safety outcomes

Hospital admissions and emergency department visits between randomisation and surgical admission in each arm will allow assessment of intervention-attributable serious adverse events.

The study flow and timeline of outcome assessments are shown in figure 1.

Figure 1. Study flow. CFS, Clinical Frailty Scale; EQ-5D, health related quality of life measure; Patient TDF, Theoretical Domains Framework; PG-SGA, Scored Patient-Generated Subjective Global Assessment (Short Form); TAPA, Telephone Assessment of Physical Activity; WHODAS, WHO Disability Assessment Schedule measuring disability free survival.

Sample size

Our target sample size for the pilot trial is 144 patients. This sample size is adequate for each of the three feasibility outcomes: (1) Recruitment of 144 participants over 6 months at our five sites will demonstrate our ability to recruit, on average, 6 participants per site per month. With this recruitment rate, the expected full trial sample size (700–900 participants, dependent on sample level common SD for the WHODAS outcome⁶¹ will be achievable within 12–18 months at the 11 sites planned for the larger trial; (2) Proportion of participants adherent to the intervention can be estimated with a 95% CI with a lower limit of 0.768 (assuming lowest demonstrated adherence similar to our virtual platform to date: 85%;^{62 63} and (3) Proportion retained at follow-up can be estimated with a 95% CI with a lower limit of 0.851 (assuming a rate>90% based on previous work.)^{27 64}

Recruitment

Our pragmatic approach to recruitment will be a key feature evaluated in this pilot trial. At each site, we will use a multipronged (surgeon referral, patient self-referral and candidate identification from surgical clinic lists) approach to recruitment as we would expect to use in future usual care settings. At the surgery clinic-level, directed education and staff-facing materials about prehabilitation and the STRIVE pilot trial will be provided to surgeons and clinic staff. This will include who to refer, how to refer and when to refer. This approach mimics routine care where clinicians would be expected to refer patients for prehabilitation (as they would for medical optimisation such as an anaesthesiology or medicine consultation). Public-facing materials (posters, pamphlets) will be posted in clinics and included in surgical information packets provided to patients consenting to surgery. This will empower patients to self-refer following a surgical consultation and decision to proceed with surgery. Where centres have established mechanisms to actively identify potential prehabilitation candidates, the research team will contact patients to recruit them in accordance with patient contact rules established by research ethics boards at each site. An altered approach to consent (verbal via telephone) will support pragmatic design.^{65 66}

Assignment of the intervention

The random allocation sequence will be independently computer-generated using the method of maximally tolerated imbalance⁶⁷ stratified by centre. Study personnel will access the randomisation sequence via a central web-based application to ensure allocation concealment.

Blinding

Clinicians will be blinded to allocation as will patient-reported outcome assessors and abstractors who collect routine healthcare data. Participants will be partially blinded as described in the section on control conditions through the provision of general information activity and healthy eating guides (without coaching or any active support), inclusive of informing all participants that they are being enrolled in a trial to test prehabilitation strategies.

Data collection and management

A standardised Electronic Data Capture (EDC) system specifically developed for this study will be used for data collection. Data collection will be completed by research personnel or the site investigator over the telephone. Postdischarge data will be collected via telephone by authorised research staff at the central coordinating centre and subsequently entered into the EDC. Appropriate security measures will be taken to authorise study site personnel to use unique usernames and passwords prior to entering any data in the EDC. The study data will be housed on a secure in-house server in a privacy legislation compliant manner throughout the duration of the study and up to 10 years after study completion.

Intervention group participants will track their prehabilitation adherence via the online programme and by using a paper log that is couriered to them. Additional adherence data will be collected by prehabilitation coaches during weekly coaching calls.

In the uncommon event that a randomised participant does not go on to have their planned surgery within 12 weeks of enrolment, we will define post-enrolment date 84 as the surgery date to inform outcome ascertainment timing. The STRIVE Trial Investigative Team and the Ottawa Methods Centre will have access to the trial data set.

Data analysis

Descriptive statistics will be used to report participants’ baseline characteristics, by study arm (mean and SD for continuous variables or median and IQR for skewed distributions and frequency and proportion for categorical variables).

Overall and for each centre, we will calculate the mean number of participants enrolled monthly along with SD and 95% CIs for the mean and the SD. For the proportion of participants who were adherent to the intervention and the proportion of participants with complete primary outcome data at 30 days, we will estimate proportions with 95% binomial CIs.

Patient-reported, clinical or routinely collected outcome data will not be analysed by allocation as the STRIVE pilot trial is being conducted within the framework of an internal pilot design. Outcome data collected in the pilot will move into the full-scale trial, if feasibility is demonstrated and no substantive changes to the study protocol or intervention design are required. Migration of outcome data will require endorsement by the study’s independent data safety monitoring board (DSMB). A sample-level (ie, the sample of all randomised patients in both arms) common SD and 95% CI for the WHODAS scale will be estimated to inform expected common variance in the larger trial which will inform the final sample size for the full trial.⁶¹

Ethics and dissemination

Each participant will be read the informed consent form by a trained research assistant over the telephone in addition to being given the opportunity to read it via email and given time to consider and ask questions about the information in the informed consent form (online supplemental material 1). The trained research assistant must obtain verbal informed consent from the participant before any study procedures occur. Any modifications to the protocol which may impact on the conduct of the study, potential benefit of the patient or may affect patient safety, including changes of study objectives, study design, patient population, sample sizes, study procedures or significant administrative aspects will require a formal amendment to the protocol. Such amendments will be reviewed and approved by The Ottawa Health Sciences-Network Research Ethics Board.

Dissemination plans include local, national and international presentations at scientific conferences as well as submission to peer-reviewed scientific journals. Press releases will engage lay media and social media will be further leveraged to disseminate results. Development of brief overviews and visual abstracts will occur and will be shared with study partners, patients and knowledge users.

Confidentiality

Participants’ data will be anonymised using a study identification number and stored using a protected file separated from the research data. This file will be stored on a secured hospital server where only the researchers in this study will have access to the research data.

Monitoring

An independent DSMB has been established and will meet once 50% of participants have been recruited. All adverse events that occur after enrolment during or within 30 min of participation in the intervention (exercise, protein supplementation or breathing exercises) will be documented. All protocol deviations will be documented. Serious adverse events that the principal investigator deems related to the study protocol will be reported to the REB as soon as possible. Local protocols mandate that reporting occur within 7 days if the study-related serious adverse event is unexpected and involves greater risk. Adverse events related to the participants’ underlying condition(s) and related treatment will not be collected as part of this study.

The coordinating centre will conduct monitoring sessions to review regulatory and study files including monitoring of primary outcome data that will be merged with the larger trial.