Study design

A two-parallel, evaluator-blind, single-centre, randomised controlled trial was designed to assess the effectiveness of a home-based mobile guided exercise-based cardiac rehabilitation among patients undergoing TAVR. It follows the recommendations of the Standard Protocol Items: Recommendations for Interventional Trials statement.16 The trial is executed at the homes of the participants after TAVR. The REHAB-TAVR trial is registered with Clinicaltrials.gov (NCT05989594). The study is scheduled to commence on 3 January 2024, with a planned conclusion on 31 December 2024.

Study population

The REHAB-TAVR Trial has a target enrolment of 90 patients undergoing TAVR admitted. Patients aged between 60 and 89 years, who are scheduled for discharge following TAVR, are eligible for inclusion. Box 1 shows the inclusion and exclusion criteria.

Recruitment, randomisation and blinding

Recruitment of participants

All participants will be recruited on the day before discharge from the hospital. Health professionals (doctors, nurses and physiotherapists who are the team members of TAVR) at the hospital will screen and refer to a research assistant the interested clients who meet the inclusion criteria. The research assistant will obtain informed consent from caregivers and patients prior to randomisation and trial inclusion. Participants (n=90) will be randomised after baseline assessment in the two-arm study. Outcomes will be measured at four-time points: baseline pretest (T0), 1 month after discharge (T1), 3 months after discharge (T2) and 6 months after discharge (see figure 1).

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Figure 1

Patients flow. TAVR, transcatheter aortic valve replacement.

Intervention

During hospitalisation, both the REHAB-TAVR group and the Routine-TAVR group will undergo exercise-based cardiac rehabilitation, which comprises three phases: preoperative rehabilitation, cardiac care unit rehabilitation and general ward rehabilitation. Each phase will encompass rehabilitation assessment, exercise training, safety management and health education. However, there are specific differences between the two groups in terms of discharge preparations and the management model of exercise-based cardiac rehabilitation after discharge.

REHAB-TAVR group

For the REHAB-TAVR group, discharge preparation will involve an exercise endurance test, exercise prescription guidance, motivational interviews, instruction on telerehabilitation and the provision of family and peer support(table 2). Following discharge, patients will be required to adhere to their personalised exercise prescription and attend scheduled onsite follow-ups 1 month and 3 months after discharge. The management model employed for this group is called home-based mobile guided exercise-based cardiac rehabilitation. The management approach includes weekly telephone follow-ups during the first month, followed by telephone follow-ups every 2 weeks within 2–3 months after discharge, all conducted by nurses. To monitor their progress, patients will engage in aerobic training, balance training and resistance training, wearing a wearable watch that records heart rate, step counts, sleep status and other physical data. These data will be accessible to patients, families and medical staff through an app (figure 2). The app includes five modules: data monitoring and reminder, exercise log, question inquiry, health education and interactive comments. Notably, the app will automatically send reminders to patients and their family members if the patient’s heart rate exceeds the set normal range. Additionally, patients are required to fill out an exercise log on the app, reporting their exercise status and feelings regularly. Throughout this process, the REHAB-TAVR group will receive extensive support, including family and peer support, mailing letters, institutional referrals and security management. These measures are aimed at enhancing the rehabilitation experience and promoting better patient outcomes.

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Table 2

Description of the REHAB-TAVR intervention

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Figure 2

The APP for the homed-based exercise of patients undergoing transcatheter aortic valve replacement.

Retention and adherence

To address retention concerns even before enrollment, our approach is multifaceted. We begin by thoroughly explaining the study’s requirements to potential participants, proactively identifying and addressing potential barriers, particularly for those randomised into the intervention arm. Prior to randomisation, we conduct an adherence screening to confirm each participant’s commitment. We also seek the support and involvement of family members, caregivers and personal physicians. Those unable to fully commit during this screening phase will not proceed to randomisation. On randomisation, participants will receive a well-defined schedule of all study visits, including timely reminders. In cases of missed visits, we will initiate same-day phone calls to ensure minimal disruptions. We actively engage family members and caregivers, and when applicable, we share test results and intervention progress with them. We also provide some transportation cost subsidies to facilitate participation. We anticipate potential interruptions to the study intervention, such as due to illness or hospitalisation. To allow participants a reasonable opportunity to complete the study intervention and to ensure that the physical performance outcome measures align with the intended intervention, we have incorporated limited extensions (2 weeks) into the study protocol for participants in both study arms. Our primary method for evaluating adherence is the Exercise Adherence Rating Scale (EARS) developed by Newman-Beinart et al in 2017.17 Through this scale, we will conduct a comprehensive assessment of exercise adherence behaviour, delve into the reasons behind adherence or non-adherence, and gather specific details regarding the exercise recommendations.

Outcome measures

Data collection and management

The collection of baseline data was performed in collaboration with a research assistant who is a registered nurse. Subsequent data collection for all outcomes will be carried out by student B. To streamline this process, we have implemented an electronic data capture (EDC) system that is accessible online for comprehensive data collection and management. The utilisation of the EDC system ensures the confidentiality of data throughout the study. On obtaining written consent from each patient, they will be assigned a unique identity code. The research assistant will diligently review all data entries before validation, addressing any missing data through supplementary inquiries. For data cleaning procedures, statisticians will be blinded to group allocation, ensuring impartiality in the analysis. At the conclusion of the study, all data will be anonymised. The final trial dataset will be made available to the data monitoring committee at our hospital for further analysis. Before initiating the data collection phase, the research team provided standardised training to both the research assistants and students A and B individually. This rigorous training process serves to uphold the accuracy and consistency of data collection throughout the duration of the study.

Sample size

Using 6MWD as the primary outcome measure and adopting a two-sided significance level (α) of 0.05 with a desired power (1–β) of 0.8, we calculated the sample size using the formula designed for estimating the required sample size in a statistical test for mean differences between two groups. As per findings from 29, the disparities in 6MWD between the intervention and control groups at both 3 months post intervention and baseline were as follows: intervention group (52.1±43.9 m), control group (−4.3±38.8 m). Accounting for a 20% attrition rate, the initial sample size calculation yielded 11 participants per group. However, in pursuit of heightened statistical power, our study aims to recruit 45 patients in each group. This adjustment resulted in a power (1–β) calculation exceeding 0.95, indicating that this sample size will provide increased sensitivity and specificity, thus achieving a higher level of statistical power. Consequently, this study intends to enrol 45 patients in each group, totaling 90 patients after TAVR.

Statistical analysis

We will assess the intervention’s impact on a variety of outcome measures, encompassing quantitative, qualitative and ordinal data. Our statistical approach will be tailored to each outcome’s nature and distribution, with potential methods such as analysis of covariance (ANCOVA), repeated measures or mixed models, t-tests, Kruskall-Wallis Mann-Whitney tests, or χ² tests being considered as appropriate.

Specifically, we will use ANCOVA to analyse the intervention’s effect on the change in 6MWD at the 3-month post-randomization mark. In this analysis, the randomised treatment group will serve as the between-subject grouping variable, while baseline 6MWD, age and gender will be included as covariates. We will estimate the intervention’s impact using least-square means, and statistical tests will be conducted at a 5% significance level (two sided). Our secondary objective involves evaluating the intervention’s influence on changes in 6MWD at the 6-month post-randomization interval, as well as on SPPB scores at both the 3-month and 6-month post-randomisation points, in addition to EARS scores at the 1-month, 3-month and 6-month post-randomisation time frames. We will employ repeated measures mixed models for between-group comparisons when analysing these secondary outcomes. All statistical analyses will be performed using SPSS Statistics for Mac (V.26.0, IBM), with the significance level set at p<0.05.

We will conduct an intention-to-treat analysis, encompassing all participants randomised into groups after baseline data collection, regardless of their adherence to or receipt of the allocated intervention. This approach assumes that the majority of participants in both arms will complete the appropriate number of intervention sessions. Additionally, we will conduct a per-protocol analysis for participants who successfully complete the study without major protocol violations (eg, those who attend more than 80% of the training sessions). The per-protocol analysis will be performed as a secondary analysis if a sufficient number of participants in both arms either do not receive the intervention protocol or are lost to outcome assessment. Data from these participants, who adhere to the treatment protocols, will be included in the per-protocol analysis. To handle missing data, we will employ the multiple imputation technique, assuming that the missing data occur at random.

Economic analysis

To assess the economic implications of the REHAB-TAVR intervention, we will adopt a two-pronged approach. First, we will use the well-established and validated TEAM-HF Cost-Effectiveness Model30 to generate comprehensive cost estimates associated with the implementation of the REHAB-TAVR programme. Additional input will be gathered from interventionists and support staff to refine our cost estimations for delivering the rehabilitation intervention. Second, we will collect patient-level data throughout the 6-month follow-up period, encompassing information on medical resource utilisation, patient time allocated to rehabilitation-related activities and quality of life (measured using the EQ-5D-5L instrument) (refer to table 1). These data will serve as the basis for estimating various cost components, including direct medical costs, non-direct medical costs, indirect costs (related to patient time) and quality-adjusted survival. Ultimately, we will compare the mean costs and quality-adjusted survival observed over the 6-month follow-up period between patients randomised to receive the rehabilitation intervention and those receiving routine care. This economic evaluation of the REHAB-TAVR intervention promises to furnish healthcare managers with invaluable insights, enabling them to make well-informed decisions in the realm of healthcare management.

Adverse events

Given that the participants in this study consist of older adults who are particularly susceptible to adverse events (AEs), including falls or age-related health conditions, a robust monitoring system has been established. Any AE, whether reported by the patient, their family members, caregivers or the physiotherapist, will be promptly communicated to the research assistant.

AEs that will be reported include:

• falls necessitating medical attention;

• aggravation of pre-existing illnesses;

• escalation in the frequency or severity of pre-existing episodic events or conditions;

• the detection or diagnosis of a condition after the intervention, even if it may have been present before the study began;

• sustained and deteriorating diseases or symptoms that were evident at baseline but worsened following the study’s initiation.

On receiving notification of an AE, the research assistant will promptly notify the principal investigator. The principal investigator, in collaboration with the research team and medical professionals, will engage in discussions regarding the management and classification of the AE. The classification of AEs will be conducted in accordance with the Common Terminology Criteria for Adverse Events V.5.0. The specific classification methodology is outlined as follows:

• Grade 1 mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated.

• Grade 2 moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL).

• Grade 3 severe or medically significant but not immediately life threatening; hospitalisation or prolongation of hospitalisation indicated; disabling; limiting self-care ADL.

• Grade 4 life-threatening consequences; urgent intervention indicated.

• Grade 5 death related to AE.

Eventually, the research assistant will diligently document the event’s details using the ‘Database for AE/Serious AE’ form. This comprehensive approach ensures the thorough recording and monitoring of AEs throughout the study.

Audits and inspections

The source data/documents will be accessible to auditors/inspectors from the Ethics Committee and Clinical Research Center in our hospital. The principal investigator will answer the questions during the inspections. All involved parties will keep the participant data strictly confidential.

Patient and public involvement statement

In formulating this study, we engaged with patients from a diverse array of backgrounds to assess their comprehension and interpretation of the data collection instruments, thereby aiding in the selection of research materials. Throughout the execution of this study, all data were derived directly from patients. Patients and families were also integrated into the design of the APP, with their user experiences collected to further enhance the APP’s interface design and f functional modules.

Ethics and dissemination

The REHAB-TAVR trial is being conducted in accordance with the Declaration of Helsinki. Before recruitment, ethical approval for this study including the study protocol and all study-related materials was obtained from the Ethics Committee at Zhongshan Hospital, Fudan University (ethics approval number: B2022-062R). Any protocol amendments concerning alterations in eligibility criteria, outcomes or analysis procedures will be promptly communicated to the research team, ethical committees and the ClinicalTrials.gov Protocol Registration and Results System (PRS). Notifications to the research team and ethical committees will be conveyed through email, while updates to the protocol will be documented in the ClinicalTrials.gov PRS web template. Moreover, any changes impacting participants will be conveyed by the medical staff at Zhongshan Hospital, and Fudan University during each assessment.

Consent or assent

Participation in this study is entirely voluntary. During the recruitment process, each participant received comprehensive explanations from a proficient research assistant regarding the study’s objectives, detailed procedures and the handling of personal data. Ample time was provided for participants to ask questions and seek clarification. Written informed consent (online supplemental material 1) was obtained from every participant, and they retain the right to withdraw their consent at any time, which includes the disposal of biological samples and the deletion of collected data, without any adverse impact on their healthcare or other aspects of their well-being. Participants will also receive full disclosure of the assessment results.

Confidentiality

Data confidentiality is of utmost importance, and data collection will adhere to the Ethics Committee’s guidelines at Zhongshan Hospital, Fudan University. Certainly, digital data devoid of patient identity information will be securely stored in password-protected files. Access to source data/documents will be restricted to authorised study team members and auditors/inspectors from the Ethics Committee and Clinical Research Center in our hospital to ensure complete confidentiality. Informed consent forms and other participant-related documents will be securely retained throughout the study and subsequently placed in locked boxes in the principal investigators' office.

Access to data

After the anonymisation of the trial dataset, the data and data collection forms of the study will be made available to any scientist who wishes to use them for non-commercial purposes, respecting participant confidentiality after an application to the principal investigator.

Dissemination policy

Our research findings will be shared through presentations at pertinent conferences and meetings, as well as through publication in peer-reviewed journals. Additionally, we are committed to disseminating our results, manuals, toolkits and other resources to the funding institutions supporting this study, such as the Clinical Research Center at Zhongshan Hospital, Fudan University, the Shanghai Municipal Health Commission and the Ministry of Science and Technology of the People’s Republic of China.