Remote Exercise Program Delivery Using a Mobile Application for Pulmonary Arterial Hypertension

Study Overview
=================
Brief Summary
-----------------
This study will determine the feasibility of a mobile application-based home exercise rehabilitation program for patients with pulmonary hypertension.

Detailed Description
-----------------
Pulmonary rehabilitation programs that incorporate exercise training are an important component of optimal medical care for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), which improves exercise performance, quality of life, and may even modify disease progression. To date, no studies have utilized mobile health (mHealth) technology to provide exercise program interventions in the pulmonary hypertension population. Leveraging mobile technology, such as smartphones or tablets, to administer a home-based exercise rehabilitation program could improve patient access, satisfaction, and participation, while providing sustained physiologic benefits and incurring major cost savings compared to inpatient or outpatient-based supervised programs. This study hypothesis is that a home-based exercise program delivered by a mobile app will be feasible and safe for PAH/CTEPH patients. The secondary outcomes assessed will explore whether there are changes in exercise capacity, health-related quality of life, and right ventricular function, compared to standard care.

Official Title
-----------------
Remote Exercise Program deliVery Using A Mobile Phone Application for Patients With Pulmonary Arterial Hypertension (REVAMP): a Pilot Randomized Trial

Conditions
-----------------
Pulmonary Hypertension

Intervention / Treatment
-----------------
* Behavioral: Exercise Intervention
* Behavioral: Standard Care


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years old. Either 2 OR 3 Diagnosis of PAH by a right heart catheterization with documented mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg and a pulmonary vascular resistance (PVR) > 3 wood units. Diagnosis of CTEPH with mPAP ≥ 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg and a pulmonary vascular resistance (PVR) > 3 wood units. Evidence of thromboembolic occlusion of the pulmonary arterial system. The patient must be deemed inoperable for, or have persistent pulmonary hypertension after, thromboendarterectomy. Must own a mobile smart phone or tablet and have internet access at home. Stable doses of PAH medications for ≥3 months. Changes to diuretic doses or anticoagulation within 3 months are permitted. Exclusion Criteria: High-risk PAH, defined as REVEAL 2.0 score ≥9 or high-risk according to the 2015 European Society of Cardiology/European Respiratory Society (ESC/ERS) guidelines table. Syncope in previous 3 months. Unstable coronary artery disease. Canadian Cardiovascular Society Class ≥ II angina. Myocardial infarction in the past 3 months. Symptomatic coronary artery disease with ≥50% stenosis on angiogram. Moderate obstructive lung disease defined as forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio < 0.7 and FEV1 < 70% predicted. Active treatment for malignancy other than non-melanoma skin cancer in past 12 months. Life expectancy < 12 months. Actively listed for lung transplantation. Cognitive, sensory, or musculoskeletal limitation that precludes participation in an exercise program, according to the investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mobile application-based home exercise intervention<br>The exercise program will be administered over 12 weeks through the Ethica mobile app. Participants will perform exercise sessions at home guided by instructional video accessed via Ethica, six days per week. The program will include a combination of education, endurance, strength, and respiratory muscle training. The Ethica mobile app will provide a daily alert and a daily exercise video. There will be background monitoring of step counts and actigraphy will be monitored for one week intervals at baseline, at week six, and at week twelve. | Behavioral: Exercise Intervention<br>* The Ethica mobile app will provide a daily alert accompanied by a short educational statement about PAH, disease self-management tips, dietary and nutritional advice, goal setting, and a motivational statement to encourage patients. Participation with each session will be assessed by a mobile app-embedded survey administered at the end of the day. Patients will be presented with weekly alerts to complete validated patient-reported quality of life questionnaires using the EmPHasis-10 and the Living with Pulmonary Hypertension Questionnaire, as well as the PRAISE self-efficacy score for pulmonary rehabilitation. The app will also ask patients to report their WHO/NYHA functional class every week. Using in-app buttons, participants can log adverse events associated with each exercise session.<br>|
| Active Comparator: Standard care<br>No supervised exercise session will be performed. Symptoms and quality of life will be monitored in the same manner as the intervention group, and participants will receive the same educational message alerts through the Ethica app as the exercise intervention group. | Behavioral: Standard Care<br>* Participants will be provided usual care administered at the PH clinic at the University of Calgary and no supervised exercise session will be performed.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of the mobile application-based home exercise program | Feasibility will be defined as all of following: Recruitment of 20 patients in an 10 month period (2 per month), Consent ratio >30% (number who consent/number of eligible patients) Dropout rate < 20% Patient adherence to the exercise program >50%. Adherence will be expressed as average number of sessions completed per week over a 3-month period. A total adherence of >70% will be considered excellent, 50-70% will be considered acceptable | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Safety will be determined by patient-reported adverse events and serious adverse events. | 12 weeks | 
| Change in six-minute walking distance (6MWD) from baseline (relative and absolute). | Measured according to American Thoracic Society guidelines for 6MWD | Baseline, 12 weeks | 
| Change in maximal oxygen consumption (V'O2 peak) | Measured by incremental symptom-limited cardiopulmonary exercise test. | Baseline, 12 weeks | 
| Change in oxygen pulse (O2 pulse) | Measured by incremental symptom-limited cardiopulmonary exercise test. | Baseline, 12 weeks | 
| Change in ventilatory efficiency (V'E/V'CO2 slope and nadir) | Measured by incremental symptom-limited cardiopulmonary exercise test. | Baseline, 12 weeks | 
| Change in echocardiographic markers of right ventricular size and function. | Measured with 2-dimensional and 3-dimensional transthoracic echocardiography | Baseline, 12 weeks | 
| Change in EmPHasis-10 score from baseline. | EmPHasis-10 is a simple 10-item disease-specific quality of life measurement. Scale 0-50. Higher EmPHasis-10 scores reflect worse quality of life. | Weekly for 12 weeks | 
| Change in PRAISE self-efficacy score. | Pulmonary Rehabilitation Adapted Index of Self-Efficacy (PRAISE) score is a validated self-efficacy score designed for the pulmonary rehabilitation population and is composed of 15 items. Each item is scored from 1 to 4 with a total range from 15 to 60. Higher scores indicate higher levels of self-efficacy. | Weekly for 12 weeks | 
| Change in Living with Pulmonary Hypertension score from baseline. | Living with Pulmonary Hypertension is a disease-specific quality of life score that is more widely validated than EmPHasis-10. Living with Pulmonary Hypertension questionnaire comprises 21 items and is responded to on a 6-point Likert scale ranging from 0 'No' to 5 'very much'. The total score ranges from 0 to 105. Higher scores indicate that the patients are more affected by their medical condition (worse quality of life). | Weekly for 12 weeks | 
| Change in N-terminal-pro-brain natriuretic peptide (NT-proBNP) from baseline. | NT-proBNP is a blood biomarker of right ventricular dysfunction. | Weekly for 12 weeks | 
| Proportion of patients improving at ≥1 World Health Organization/New York Heart Association (WHO/NYHA) functional class. | WHO/NYHA functional class is a subjective measure of functional capacity and symptoms. | Weekly for 12 weeks | 
| Patient Satisfaction and Usability Questionnaire. | This is a custom made questionnaire with qualitative open-ended questions and questions on a 5-point Likert scale from 1 (Very Dissatisfied) to 5 (Very Satisfied). Information will be used to refine the app and the exercise program for a subsequent trial. | Weekly for 12 weeks | 
| Change in background step counts and/or actigraphy from baseline. | This will serve to monitor study groups for baseline activity level as well as overall increased activity according to allocation. | Baseline, 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pulmonary Rehabilitation, Mobile-based home exercise program