REACTION-VAD Trial: Remote Exercise Training Via Telemedicine in Patients With Long-Term Ventricular Assist Devices

Introduction Although cardiac rehabilitation is recommended in patients with a durable Left Ventricular Assist Device (LVAD), approximately 50% of candidates cannot attend in-person programs due to geographical dificulties.

Study Rationale and Design The RE-ACTION-VAD Trial is the first multicenter randomized controlled trial designed to evaluate the efficacy and safety of a remote conditioning exercise program in patients with recent implantation of a durable Left Ventricular Assist Device (LVAD).

A total of 78 patients will be enrolled and randomized in a 1:1 ratio to:

1. Remote conditioning group: patients will undergo a three-month home-based program including aerobic, resistance, and respiratory training. Follow-up will be conducted through Telemedicine (mobile application and a smart watch); or 2. Usual care group: patients will receive written general exercise recommendations.

The primary objective is to assess whether there is an improvement in the distance covered on the 6-minute walk test at 6-month follow-up. Secondary objectives include evaluation of safety, and improvements in cardiopulmonary exercise parameters, quality of life questionnaires, frailty scales, and psychological questionnaires.

Intervention Logistics

The 12-week program is divided into an initial educational phase and a remote phase:

1. Educational Phase (Week 1): Three in-person sessions to train patients on exercise execution, load management, and the use of respiratory devices. 2. Remote Phase (Weeks 2-12): Individualized home routines including aerobic training, strength training, and respiratory.

Quality Assurance and Monitoring Plan

To ensure the integrity and standardization of the intervention across the 10 participating centers, the following quality measures are implemented:

* Site Monitoring: The study has contracted a Contract Research Organization (CRO), to perform clinical trial monitoring and auditing over a three-year period. * Standardization of Procedures: Researchers from all centers are required to complete a rotation at the Hospital Ramón y Cajal Rehabilitation Unit to unify exercise protocols. Monthly supervision meetings are held to evaluate compliance and resolve clinical doubts.

Safety monitoring board: independent adverse event assessment blinded to the intervention group.

• Technical Validation: The mobile platform utilized for monitoring holds the requisite certifications, ensuring technical reliability and data security.

Data Management and Registry Procedures

* Data Entry and Validation: Data is captured using an electronic data capture system. The system includes predefined rules for data ranges and consistency to minimize entry errors. * Source Data Verification (SDV): Investigators may cross-reference data from the electronic data capture system with hospital medical records to ensure accuracy, completeness, and representativeness. * Data Dictionary: A comprehensive data dictionary is maintained within the study's electronic data management system, encompassing variables such as anthropometric measures, cardiopulmonary exercise test (CPET) parameters (VO₂ peak, VE/VCO₂, RER), 6-minute walk test (6MWT) distance, biomarkers (NT-proBNP, CA125), and validated quality-of-life scales (KCCQ, MLHFQ). * Audit Trails: the electronic data capture system provides automated audit logs to track all data manipulations and user activity, ensuring full traceability.

Sample Size Assessment The study is powered to detect a clinically relevant difference of 35 meters in the 6MWT. Based on a standard deviation of 50 meters, an alpha of 0.05, and a power of 80%, 33 patients per group (66 total) are required. To account for an expected 15% dropout rate, the total sample size is set at 78 participants.

Statistical Analysis Plan (SAP) All analyses will follow the Intention-to-Treat (ITT) principle.

* Continuous Variables: Will be compared using the Student's T-test for independent samples or the Mann-Whitney U-test for non-parametric data. * Categorical Variables: Will be analyzed using Chi-square or Fisher's Exact test. * Missing Data Plan: While the ITT principle handles participants as randomized, the study also includes monthly supervision to incentivize compliance and minimize missing data. * Significance: A p-value \< 0.05 will be considered statistically significant.

Ethics and Confidentiality The protocol was approved by the Hospital Universitario Puerta de Hierro Ethics Committee (PI 143/25). Data is codified, and the link between codes and patient identity is stored in a password-protected offline file. Upon completion, anonymized data will be deposited in the Zenodo repository.

• Program Safety [Срок оценки: 6 months]
• Cardiopulmonary Exercise Test (CPET): peak oxygen consumption (VO₂peak) [Срок оценки: 3 months]
• Cardiopulmonary Exercise Test (CPET): VE/VO₂ slope [Срок оценки: 3 months]
• Cardiopulmonary Exercise Test (CPET): oxygen consumption at the first and second ventilatory thresholds [Срок оценки: 3 months]
• Cardiopulmonary Exercise Test (CPET): ventilatory equivalents [Срок оценки: 3 months]
• Cardiopulmonary Exercise Test (CPET): Oxygen Uptake Efficiency Score (OUES) [Срок оценки: 3 months]
• Cardiopulmonary Exercise Test (CPET): Respiratory Exchange Ratio [Срок оценки: 3 months]
• Cardiopulmonary Exercise Test (CPET): oscillatory patterns [Срок оценки: 3 months]
• Quality of life (QoL): Kansas City Cardiomyopathy Questionnaire (KCCQ). [Срок оценки: 3 months]
• Quality of life (QoL): Minnesota Living with Heart Failure Questionnaire (MLHFQ). [Срок оценки: 3 months]
• Frailty screening (FRAIL scale) [Срок оценки: 3 months]
• Fried physical frailty phenotype [Срок оценки: 3 months]