REHAB Fontan Failure: A Trial of Cardiac Rehabilitation

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the impact of cardiac rehabilitation on Fontan failure patients' exertional tolerance, frailty, and quality of life. Among patients with Fontan failure, will cardiac rehabilitation increase average daily steps compared to usual care? Among patients with Fontan failure, will cardiac rehabilitation improve exertional tolerance (as measured by cardiopulmonary exercise testing), frailty, and self-reported quality of life metrics compared to usual care?

Detailed Description
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REHAB Fontan Failure is a a multi-center, non-blinded, randomized clinical trial evaluating the effect of cardiac rehabilitation compared to usual care on exercise tolerance among adults with Fontan failure. Eligible study subjects will be identified from clinical chart review and study informational fliers will be sent to Adult Congenital Heart Disease (ACHD) cardiologists at all centers. Fontan failure patients being evaluated for outpatient care at ACHD centers and meeting eligibility criteria will be enrolled and randomly assigned to either cardiac rehabilitation or usual clinical care.

Official Title
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RCT of the Effects of Cardiac reHABilitation (REHAB) Among Patients With Fontan Failure

Conditions
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Heart Failure Congenital, Single-ventricle

Intervention / Treatment
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* Behavioral: Cardiac rehabilitation
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fontan failure, defined as history of a Fontan procedure and at least one of the following: systemic ventricular EF <50% (by echocardiography, cardiac magnetic resonance imaging, or computer tomography), protein losing enteropathy, plastic bronchitis, chronic loop diuretics prescribed by ACHD Cardiologist, and/or peak VO2 < 50% predicted (by FRIEND equation) Age >= 18 years old Exclusion Criteria: Inotrope-dependence Symptomatic, uncontrolled arrhythmias Pregnancy Contraindication to cardiac rehab or already enrolled in cardiac rehabilitation Inability to comply with the protocol Recent (<3 months) planned Fontan pathway percutaneous or surgical intervention Resting hypoxemia with baseline oxygen saturation <80%

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: At enrollment, participants will be randomized in a 1:1 ratio to cardiac rehabilitation or usual care using randomly permuted blocks of 2, 4, and 6. The randomization will be stratified by study site and time from Fontan palliation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiac rehabilitation<br>For patient randomized to cardiac rehabilitation, the ACHD clinician will place the referral after they and the patient have seen the group assignment. All participants will be referred to Heart Fit for Life community-based cardiac rehabilitation program in Palo Alto, CA. Cardiac rehabilitation will be offered as an in-person, hybrid, or completely virtual program for Stanford participants and will be entirely virtual for Vanderbilt participants. Participants will attend 3 sessions per week for 12 weeks. Participants will receive weekly email reminders via the electronic medical record to encourage participation. The study protocol pertains only to referral to cardiac rehabilitation. All other aspects of the cardiac care will be at the discretion of clinicians. All study participants will receive a Fitbit for daily activity tracking. | Behavioral: Cardiac rehabilitation<br>* Cardiac rehabilitation is a multifaceted, comprehensive therapeutic intervention of personalized, supervised exercise training that is beneficial and well-studied among patients with non-ACHD heart failure and has consistently been shown to improve QOL. Unfortunately, cardiac rehabilitation has been underutilized with an overall participation <50% of eligible patients despite international guidelines advocating for more consistent deployment of cardiac rehabilitation. A major a barrier to cardiac rehabilitation is access, as CMS-mandates a physician be within 3 minutes of the rehabilitation facility to assure insurance reimbursement. This mandate limits isolated, outpatient cardiac rehabilitation programs, especially in rural communities.<br>|
| Active Comparator: Usual care<br>For patients randomized to the usual care (no cardiac rehabilitation group), cardiac rehabilitation will not be initiated between randomization and for up to 16 weeks following randomization. The study protocol controls only referral to cardiac rehabilitation. All other aspects of the cardiac care, such as titration of guideline directed medical therapy will be at the discretion of clinicians. All study participants will receive a Fitbit for daily activity tracking. | Other: Usual care<br>* For participants randomized to the usual care (no cardiac rehabilitation group), cardiac rehabilitation will not be initiated between randomization and for up to 16 weeks following randomization. The study protocol controls only referral to cardiac rehabilitation. All other aspects of the cardiac care, such as titration of guideline directed medical therapy will be at the discretion of clinicians.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average daily step count | Average daily step count during the intervention period measured by Fitbit 3 activity tracker | 120 days (+/- 45 days) post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 5-meter timed walk as a measure of slowness |  | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in exercise time as a measure of exhaustion | Exercise time on cardiopulmonary exercise testing | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in respiratory exchange ratio (RER) as a measure of exhaustion | RER on cardiopulmonary exercise testing (exhaustion) | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in mini-nutritional assessment short form (MNA-SF) score | Nutrition score as measured by MNA-SF; range 0-14; malnourished 0-7, 8-11 at-risk, and 12-14 normal nutritional status | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in body fat percentage | Body fat percentage is a measure of body composition | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in grip strength |  | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in patient reported physical activity questionnaire score |  | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) scale score | KCCQ-12 is a 12 question questionnaire, participants completed questionnaire about how heart failure affected their life over the past 2 weeks. The scale has 4 domains: symptom frequency, physical limitation, social limitations and quality of life for a total possible transformed score of 0 to 100 where 100 denotes the highest health status. A positive change from baseline indicates improvement. | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change Patient Health Questionnaire-2 (PHQ-2) score | Mood assessment (Range 0-6, higher score indicates higher risk of depression, >=3 suggestive of depression) | Baseline and 120 days (+/- 45 days) post-randomization | 
| Average daily active minutes | Total average daily active minutes from Fitbit | Baseline and 120 days (+/- 45 days) post-randomization | 
| Average daily active minutes of moderate-high intensity activity | Average daily active minutes of moderate-high intensity activity from Fitbit | Baseline and 120 days (+/- 45 days) post-randomization | 
| Average daily sedentary minutes | Average daily sedentary minutes from Fitbit | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in peak respiratory oxygen uptake (VO2) | Peak VO2 on follow-up cardiopulmonary exercise testing, adjusted for baseline | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in oxygen (O2) pulse | O2 pulse on follow-up cardiopulmonary exercise testing, adjusted for baseline | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in minute ventilation/carbon dioxide production (VE/VCO2) | VE/VCO2 on follow-up cardiopulmonary exercise testing, adjusted for baseline | Baseline and 120 days (+/- 45 days) post-randomization | 
| Change in anaerobic threshold | Anaerobic threshold on follow-up cardiopulmonary exercise testing, adjusted for baseline | Baseline and 120 days (+/- 45 days) post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fontan, Single ventricle, Cardiac rehabilitation