Impact of online support of physical activity management using a wearable device on renal function in patients with acute coronary syndrome: a randomized controlled trial protocol

Objective

The primary objective of this study is to determine the impact of remote support for PA management using a wearable device on renal function in patients with ACS. The secondary objectives are to determine the impact of this intervention on other factors such as cardiac and physical function as well as QOL, and to determine whether it can be an alternative intervention for patients with ACS who have difficulty participating in outpatient CR.

Clinical implications

This study will provide evidence regarding the effectiveness of remote support for PA management in renal protection after ACS, which may improve survival and recurrence rates, prevent dialysis, and reduce medical and nursing care costs for patients with ACS. The validation results of this study will provide important scientific information for establishing a novel CR strategy that can be adopted by many patients with ACS who have difficulty participating in outpatient CR.

Study design

The study design will be an open-label, two-arm, parallel, randomized control trial (Fig. 1). The study protocol conforms to the 2017 CONSORT NPT Extension and the study intervention is described in accordance with the CONSORT-EHEALTH.

Ethics approval

This study received approval from the Ethics Committee of Fukushima Medical University (Approval No. REC2023-174).

Study eligibility and recruitment

The inclusion criteria for patients in this study are as follows: (i) patients with ACS who underwent percutaneous coronary angioplasty and inpatient CR, (ii) age ≥18 years at the time consent was obtained, (iii) inability to participate in outpatient CR after discharge, (iv) having a smartphone, and (v) agreeing to participate in this study after receiving verbal and written explanations from the researchers. Written consent was obtained from all participating patients in this study. The exclusion criteria are as follows: (i) lack of independence in activities of daily living, (ii) unstable angina, (iii) uncontrolled arrhythmia causing hemodynamic abnormalities, (iv) severe valvular disease, (v) uncontrolled diabetes, (vi) other diseases that contraindicate the use of exercise therapy, (vii) undergoing dialysis, (viii) other acute diseases or indications for surgical treatment, (ix) dementia, and (x) inability to make regular outpatient visits to the study site after discharge.

Researchers in Southern Tohoku General Hospital and Ohta Nishinouchi Hospital, which are the institutions conducting the study, will recruit study participants who have the potential to meet the eligibility criteria. The principal investigator of Fukushima Medical University, which is the institution responsible for the research, will oversee and manage patient enrollment.

Randomization and blinding

Randomization allocation will be performed on the web using the UMIN INDICE cloud (https://www.umin.ac.jp/indice/cloud.html). Allocation will be completed within 2 weeks of initiation of inpatient CR. This study will not be blinded. Adjustment factors for allocation will be age (<60 years vs. ≥60 years), sex (male vs. female), and highest creatine kinase level (<3,000 U/L vs. >3,000 U/L).

Intervention

Online support for PA management will begin at the time of discharge; additionally, patients in the intervention group will manage their own PA based on educational support provided by the physical therapist under the supervision of the primary physician (Fig. 2). The physical therapist administering the intervention must have ≥1 year of experience in physical therapy for patients with CVD, including ACS, or be a registered instructor of CR by the Japanese Association of Cardiac Rehabilitation (https://www.jacr.jp/en/).

Online support for PA management

Patients in the intervention group will receive a wrist-worn wearable device (Fitbit Inspire 3, Fitbit, Inc, San Francisco, CA, USA) after assignment, and a web application (Recaval, SapplyM, Inc., Tokyo, Japan) for PA management will be downloaded to their smartphones. Data regarding PA and pulse rate obtained from the wearable device will be transmitted in real time via the application to the tablet device of the physical therapist in charge of the research facility. The wearable device is designed to locally store data until an internet connection is available. In addition to this biometric monitoring, the web application has chat and report feedback functions that allow two-way communication between patients and medical professionals. Patients will be instructed to wear the wearable device unless they are bathing or charging the device. Moreover, patients will be instructed to enter their daily blood pressure and self-records of subjective symptoms into the application, which will also be monitored daily by the physical therapist. Using this web application, patient information is completely anonymized; each patient is assigned a specific ID. In addition, this web application has a robust access restriction function. Only the interventionists at each research facility are only given access to the patient data of their own institution and have no access to the patient data of other research institutions.

At the beginning of the intervention and at 2-week intervals thereafter, the physical therapist will provide the patient with a summary report of daily vital sign data, including educational comments and praise commending the achievement of PA and activity pulse rate goals, through the app. Regarding the target PA value, which is the basis of the educational support, the patients will be assigned a target of ≥5,000 daily steps, referring to a previously reported cutoff value for the number of steps per day that affects improvement of renal function in patients with ACS (Sato & Kohzuki, 2021; Sato et al., 2021). Further, this target can be achieved without worsening of vital signs or subjective symptoms. For example, if the weekly average daily step count is <5,000 steps/day, a smaller target of 1,000 steps/day is set for the next week and thereafter, which allows the patient to achieve the goal of ≥5,000 steps/day in incremental stages. As a safety management measure, the target values for pulse rate during activity and duration of activity above moderate intensity are set according to each patient’s results of the baseline cardiopulmonary exercise test and Karvonen’s formula (Makita et al., 2022). Table 1 shows the criteria for discontinuation of the intervention.

Additionally, while monitoring daily PA, pulse rate, and self-recorded data regarding blood pressure, body weight, and subjective symptoms, the physical therapist will check the status and provide educational support for PA modification using the chat function of the application as required in case of the following scenarios:

• The pulse rate during activity exceeds the target pulse rate by 20 beats/minute for >10 min

• The pulse rate during PA falls below 50% of the target value for >5 consecutive days

• The patient does not wear an activity monitor for >5 consecutive days

• The patient’s self-recorded data indicate worsening subjective symptoms, including chest pain, shortness of breath, or fatigue

• The patient’s has questions or complaints regarding PA management or disease management

• The physiotherapist or physician in charge considered it necessary.

Furthermore, interviews will be conducted by telephone or via the ZOOM web conferencing service, as necessary.

Usual care

All patients in both groups will receive usual care, including patient education, medications, outpatient visits, and laboratory tests upon discharge, within the relevant scope. However, if patients wish to participate in outpatient CR during the observation period, their wishes will be respected, and they will be allowed to participate in outpatient CR after consultation with their physician. In this case, the patient will not be excluded from the study and will continue to receive “intervention and outpatient CR” in the intervention group and “usual care and outpatient CR” in the control group.

Outcome assessment

Table 2 describes the outcome measures for this trial. Patient characteristics and baseline measurements will be assessed at discharge (∼2 weeks after the onset of ACS) and reassessed after 3 months.

The primary outcome of this study will be the eGFR based on serum cystatin C (eGFRcys). In general clinical practice, the eGFR based on serum creatinine is widely used as an index for assessing renal function. However, PA, including exercise, can alter serum creatinine levels via changes in skeletal muscle mass. Therefore, cystatin C, which is independent of skeletal muscle mass, is preferred when examining the effects of PA on renal function (Séronie-Vivien et al., 2008; Poortmans et al., 2013). The eGFRcys will be estimated using the Japanese Society of Nephrology equation as follows:

eGFRcys (mL/min/1.73 m²) = 104  × Cystatin C^−1.019 × 0.996^Age × 0.929 (if female)–8 (Horio et al., 2013).

This study will perform between-group comparisons of eGFRcys at 3 months adjusted for baseline values. eGFR decline after ACS may be particularly steep during the first 90 days after onset (Hillege et al., 2003). It is important to examine the inhibitory effect on eGFR decline during this period; accordingly, we set a 3-month follow-up period for this study. Most previous studies on the impact of outpatient CR on eGFR have similarly set a 3-month intervention and observation period (Toyama et al., 2010; Takaya et al., 2014; Hama et al., 2018; Sasamoto et al., 2021; Hama et al., 2022). Therefore, the follow-up period can be considered reasonable.

Table 2:

All outcome measures and assessment schedule for this study.

CPET, cardiopulmonary exercise test; EQ-5D-5L, Euro QOL 5-dimensions 5-levels; eGFRcreat, estimated glomerular filtration rate calculated from serum creatinine; eGFRcys, estimated glomerular filtration rate calculated from serum cystatin C; LPA, light-intensity physical activity; MPA, moderate-intensity physical activity; QOL, quality of life; SB, sedentary behavior; VPA, vigorous-intensity physical activity.

	Baseline	3-month
Characteristics: sex, age, alcohol consumption history, smoking history, location of coronary artery stenosis, Killip classification, contrast fee, medical history, comorbidities, echocardiography, length of hospital stay, height	•
Body conditions: weight, body mass index, resting blood pressure, resting pulse rate	•	•
Physical function: CPET and grip strength	•	•
Blood biochemical tests: BNP, urea nitrogen, cystatin C, creatinine, glomerular filtration rate (eGFRcys and eGFRcreat), albumin, triglycerides, HDL-cholesterol, LDL-cholesterol, hemoglobin, blood sugar	•	•
Urinalysis: Urine albumin/creatinine ratio	•	•
Physical activity: step count, SB, LPA, MPA, VPA	•	•
QOL: EQ-5D-5L	•	•
Medication
Adverse events
(Intervention group only) Fitbit data: daily sleep time and heart rate (maximum, minimum, and average)

DOI: 10.7717/peerj.19067/table-2

Secondary outcomes will include the urine albumin/creatinine ratio (ACR), BNP, average step count, peak oxygen uptake (VO2) based on a symptom-limited cardiopulmonary exercise test (CPET), Euro QOL 5-dimensions 5-levels, and incidence of adverse events. In addition, blood biochemical analysis data such as urea nitrogen; albumin; triglycerides; high- and low-density cholesterol; hemoglobin; and blood glucose will be collected. These outcome measures will be assessed concurrently with the primary evaluation. In the symptom-limited CPET, to avoid overloading the cardiovascular system after ACS, the exercise load is terminated when the gas exchange ratio reaches 1.2, which is defined as the peak point, even before reaching the symptom limit (Sato et al., 2023).

PA assessment will be performed immediately after discharge and after 3 months for a 7-day period. The Active Style Pro HJA-750 (Omron Healthcare Company; Kyoto, Japan), which has a 3-axis accelerometer that has been validated and shown to be highly reliable (Oshima et al., 2010; Ohkawara et al., 2011), will be used to evaluate PA and the average number of steps. Sedentary behavior, light-intensity PA, moderate-intensity PA, and vigorous-intensity PA will be defined as PA of ≤1.5 metabolic equivalents (METs), >1.5 and <3.0 METs, ≥3.0 and <6.0 METs, and >6.0 METs, respectively (Bull et al., 2020); moreover, the time spent wearing the device will be collected. To avoid the impact of checking PA on increasing PA levels, the researcher sets the device to prevent displaying the PA data. The patients will be instructed to wear the accelerometer at all times except when sleeping and bathing. If the time the device is worn is <10 h per day, activity data for that day will be excluded. The minimum number of days required for evaluation is defined as “4 days or more”, which is more than half of the 7 days (Fig. 3). Patients will return the accelerometer to the hospital by mail at the end of that 7-day PA measurement period. The principal investigator at each hospital will transfer PA data from the accelerometer to the computer via a reader (HHX-IT4, Omron Healthcare Company; Kyoto, Japan).

Other parameters

To explain the baseline characteristics of the patients, we will investigate information on sex, age, drinking history, smoking history, site of coronary artery stenosis, Killip classification, contrast agent dose, medical history, complications, length of hospital stay, height, and weight from the electronic medical record at the time of registration. Moreover, we will investigate the left ventricular ejection fraction evaluated by echocardiography at the time of discharge.

Statistical analysis

In this study, the analysis will involve an intention to treat analysis. Therefore, patients’ consent will be obtained to use 3-month post-assessment information derived from the observed clinical data in the event of dropout or poor adherence in the intervention arm. Regarding background information of participants, discrete data, including frequencies, proportions, and 95% confidence intervals, will be calculated for each group. For continuous data, the mean, standard deviation, and 95% confidence interval will be calculated for each group.

The primary outcome, eGFRcys, will be examined using analysis of covariance (ANCOVA), with adjustment for baseline values as covariates for the least squares mean of eGFRcys at 3 months. Secondarily, between-group comparisons of the change in eGFRcys will be performed in the same way.

The secondary endpoints of ACR, BNP, average number of steps, peak VO2, and EQ-5D will be analyzed using ANCOVA, with adjustment for baseline values. Between-group comparisons of the incidence of adverse events will be performed using the χ-square test.

All statistical analyses will be performed using SPSS version 29.0 (IBM Corp., Armonk, NY, USA). Statistical significance will be set at an alpha-level of 0.05.

Sample size calculation

To determine the impact of online PA management support on eGFRcys, we will examine between-group differences in eGFRcys. Since there have been no reports of a clinically meaningful minimum difference in eGFRcys among patients with ACS, we arbitrarily assumed that the between-group difference in eGFRcys after 3 months would be five mL/min/1.73 m². If the standard deviation of eGFRcys in both groups is set to be 16.0 in reference to our previous study (Sato et al., 2019), the effect size was 0.3125.

Subsequently, assuming that between-group comparisons of eGFRcys after 3 months would be performed using ANCOVA with baseline values as covariates, G*Power 3.1 was used to calculate the required sample size with an effect size f = 0.3125, alpha = 0.05, and power = 0.8. The results showed that 83 cases were detected. Accordingly, we calculated that the required sample size was 83 cases, and the target number of cases was set at 88 (44 in the intervention group and 44 in the control group), taking into account the possibility of dropouts (5%) in both groups.