Description

Chronic obstructive pulmonary disease is a disabling respiratory condition and a leading cause of mortality worldwide. Suggested treatments are mainly symptomatic and aim to stabilize the progression of the disease. However, a major consequence of COPD is reduced exercise tolerance, which can lead patients to avoid physical activity, further inducing progressive muscle deconditioning and disabling dyspnea.

Pulmonary rehabilitation is recommended by leading international respiratory societies as a core component of the treatment for people with chronic obstructive pulmonary disease. The effectiveness of pulmonary rehabilitation is well established, with numerous studies showing that it improves dyspnea, exercise capacity, quality of life, as well as it reduces mortality and hospital length of stay following exacerbations.

Paradoxically, as few as 5 to 10% of eligible patients undergo pulmonary rehabilitation. Some known barriers to uptake include transportation difficulties and the limited availability of PR centers.

Telerehabilitation may offer an alternative to traditional center-based programs. Results from studies evaluating the clinical benefits of telerehabilitation suggest that it is non-inferior to traditional center-based pulmonary rehabilitation. However, the clinical outcomes reported for the control groups (center-based programs) in these studies were lower than those reported in the reference meta-analysis by McCarthy et al. (2015), which established the benefits of pulmonary rehabilitation, making interpretation of the results difficult. For these reasons, it remains important to continue investigating and comparing these two different modalities.

This study primarily aims to evaluate the relative effect of a 24-session home-based telerehabilitation program compared to a center-based program in patients with chronic obstructive pulmonary disease. The primary outcome is the change in endurance exercise capacity. Secondary outcomes include changes in maximal exercise capacity, functional capacity, quadriceps maximal isometric strength, functional dyspnea, physical activity, sleep quality, self-efficacy, patient autonomy, quality of life, psychological and health status, and cognitive function. Additional outcomes include adherence, environmental impact, a health economic analysis, and a 1-year follow-up to assess hospitalizations, exacerbations, and mortality as well as others outcomes.

Study design :

This is a prospective, multicenter, randomized controlled non-inferiority trial with concealed allocation and a single-blind design (blinded evaluator). Participants will be randomly assigned to one of two groups:

Center-based pulmonary rehabilitation group (24 sessions in total over 8 weeks) : participants will attend 26 center-based visits, over eight weeks, comprising:

• One initiation center-based visit(approximately 3 hours), including an initial assessment by a blinded assessor, self management diagnostic, endurance training on a cycle ergometer, strength training, balance exercises and a leaflet containing educational information and exercise recommendations to guide the patient toward full autonomy.
• Twenty-four center-based PR sessions (approximately 1 hour 45 minutes each), including a 15-minute warm-up period, endurance training on a cycle ergometer, muscle strengthening exercises, balance exercises, as well as therapeutic patient education sessions tailored to the patient's needs based on the initial assessment. Training is adjusted according to patient tolerance and healthcare professional recommendations as follow :
• Endurance training on the cycle ergometer (15 to 45 minutes per session).
• Strength training and balance exercises (30 minutes per session).
• Physical activity coaching.
• Self management at the center (before or after exercise session).
• One final center-based visit (approximately 3 hours), including a final assessment by a blinded assessor, a program review, and educational reinforcement.

Home based telerehabilitation group (24 sessions in total over 8 weeks) : participants will attend 2 visits at the center and perform 24 sessions at home, over eight weeks, comprising:

• One initiation center-based visit (approximately 3 hours), including an initial assessment by a blinded assessor, self management diagnostic, endurance training on a cycle ergometer, strength training, balance exercises and a leaflet containing educational information and exercise recommendations to guide the patient toward full autonomy as well as patient education on how to use the telerehabilition system.
• Twenty-four PR sessions (approximately 1 hour 45 minutes each), including a 15-minute warm-up period, endurance training on a cycle ergometer, muscle strengthening exercises, balance exercises, as well as therapeutic patient education sessions tailored to the patient's needs based on the initial assessment. Training is adjusted according to patient tolerance and healthcare professional recommendations. Participants will receive a cycle ergometer, pulse oximeter, activity tracker, and a tablet application (TELEREHAPP) for guidance throughout the program, remote monitoring, and communication. Home-based sessions include:
• Endurance training on the cycle ergometer (15 to 45 minutes per session).
• Strength training and balance exercises (30 minutes per session).
• Physical activity coaching, including a daily step goal.
• Regular remote monitoring and support via the tablet application, with weekly check-ins from healthcare professionals.
• Self management through videoconferencing.
• One final center-based session (approximately 3 hours), including a final assessment by a blinded assessor, a program review, and educational reinforcement.

Sample size calculation for non-inferiority study:

Assuming a mean difference of 0 seconds between the two groups in the constant work rate endurance test, a non-inferiority margin of 105 seconds, a conservative standard deviation of 150 seconds, an alpha risk of 0.05, and a beta risk of 0.05, a total of 45 patients per group will be needed, totaling 90 patients.

Statistical analysis:

Categorical data will be presented as counts (percentages). Continuous descriptive data will be expressed as means (standard deviation) or medians (interquartile range), depending on their distribution. The normality of distributions will be assessed using the Kolmogorov-Smirnov test.

The analysis will be performed on an intention-to-treat basis using the last observation carried forward method. A per-protocol sensitivity analysis will also be conducted.

The relative effect of the interventions on the primary outcome and other outcomes with repeated measures will be analyzed using a mixed linear model with group (telerehabilitation or center-based rehabilitation), time of measurement (start and end of the program, 1-year follow-up), and their interaction as fixed effects factors, and participant as a random effect factor. Based on available data from the literature, analyses will be adjusted for age, use of long-term oxygen therapy, baseline 6-minute walk distance (except for analyses already including the 6MWD), functional dyspnea (except for analyses already including dyspnea), Forced Expiratory Volume in 1 Second, number of hospitalizations in the past 12 months, anxiety and depression scores (except for analyses already including these outcomes), as well as health status (except for the analysis already including this outcome).

The relative effect of the interventions on outcomes assessed only at the end of the program (e.g. environmental analysis) will be analyzed using a linear mixed model with group (telerehabilitation or center-based rehabilitation) as a fixed effect factor and participant as a random effect factor. The analysis concerning VO₂ peak will be adjusted for the same covariates as the primary outcome.

The difference in effect between groups will be expressed as a mean difference (95% CI) and interpreted according to the minimal clinically important difference specific to each outcome measure, when available in the literature.

The relative effect of the interventions on health events (exacerbations, hospitalizations, death) and program adherence will be assessed using the relative risk at 1 year (95% CI) and adjusted using the same covariates as for the primary outcome analysis. The hazard ratio for time to first exacerbation or death will also be estimated.

Health economic analysis:

Differences in costs and outcomes will be estimated using the seemingly unrelated regression method. These differences will be adjusted using the same covariates as those used in the clinical analyses of the primary outcome, in addition to the randomization arm and baseline utility score for quality-adjusted life years.

A non-parametric bootstrap will be used to represent uncertainty related to estimates for cost-effectiveness.

Analyses will be performed using GraphPad 8 and R software.