Evaluating Mobile Health Tool Use for Capturing Patient-centered Outcomes Measures in HF Patients

An Observational, Multicentre Study to Evaluate the Feasibility of a Novel Mobile Health Monitoring Platform to Capture Patient-centered Outcomes Measures Among Patients With Heart Failure (HF)

Heart Failure (HF) is a highly prevalent disease that also carries high morbidity and mortality. The Food and Drug Administration (FDA) recognizes the importance of developing patient-centric endpoints that are relevant to patients beyond mortality and hospitalizations.

Although functional status can be objectively measured by peak exercise oxygen consumption, it is difficult and impractical to implement in large clinical studies, especially in an ambulatory real-world setting. Recently, new mobile health technologies have emerged as clinical tools and offer an opportunity to overcome these challenges in measuring functional capacity and recording symptoms.

The goal of this observational study is to evaluate the feasibility of monitoring functional capacity among patients with heart failure (HF) using mobile health monitoring platforms.

Everion® and Apple Watch Series 4 and above will be used for this study. The BiovitalsHF® mobile app can capture patients' key cardiopulmonary physiological parameters, functional capacity (using activity patterns, including guided mobile-based 6MWT, audio recording) and assessment of QoL through validated PROs.

Study Overview

• Status: Terminated
• Conditions: Heart Failure

Detailed Description

Heart Failure (HF) is a highly prevalent disease that also carries high morbidity and mortality. Improvements in mortality and healthcare utilization, including hospitalizations of HF still remain the gold standard outcomes for HF drug approval. However, it is difficult to improve mortality as the only endpoint due to the variation in the age groups and comorbidities of the population and ineffectiveness to alter all-cause mortality, particularly in patients with heart failure with preserved ejection fraction (HFpEF). Considering these issues, there is a need for exploration of complimentary endpoints. The Food and Drug Administration (FDA) recognizes the importance of developing patient-centric endpoints that are relevant to patients beyond mortality and hospitalizations. Patients with HF have reduced function capacity and quality of life (QoL) and hence it is imperative to explore interventions that impact endpoints that directly measure how a patient feels or functions on a daily basis. Although functional status can be objectively measured by peak exercise oxygen consumption, it is difficult and impractical to implement in large clinical studies, especially in an ambulatory real-world setting. Other objective measures of functional status include a 6-minute walk test (6MWT) and potentially measures of activity using implanted or wearable sensors. Patient-reported outcomes (PROMs) can also be used to record and quantify symptoms but are cumbersome and impractical since significant resources are required to contact patients and administer questionnaires. It is also particularly difficult to record these and correlate with physiologic signals in real-time.

Recently, new mobile health technologies have emerged as clinical tools and offer an opportunity to overcome these challenges in measuring functional capacity and recording symptoms. These technologies are able to capture and integrate data from disparate sources from individual patients reflecting their functional status and symptomatology. These data can potentially serve as surrogate endpoints for approval of new HF therapies. A novel mobile health platform (BiovitalsHF, developed by Biofourmis) enables continuous acquisition and monitoring of multiple physiologic data (for e.g. electrocardiogram, heart rate, respiration rate, activity intensity, 3-axis accelerometer and sleep) using readily available biosensors (Everion® MD and Apple Watch will be used for this study). The BiovitalsHF smartphone app is capable of capturing patient's physiology, functional capacity (using activity patterns, including guided mobile-based 6MWT) and assessment of QoL through validated PROs.

• Study Type: Observational
• Enrollment (Actual): 67

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 529889
    • Changi General Hospital
  • Singapore, Singapore, 169609
    • National Heart Centre Singapore
  • Singapore, Singapore, 768828
    • Khoo Teck Puat Hospital
• United States
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Approximately 150 eligible subjects will be enrolled into the study. Eligible subjects will include adults with a diagnosis of heart failure (NYHA class I to class III), and screened within 30 days after Clinic Visit or hospitalization for heart failure - either as a primary or secondary diagnosis.

Description

Inclusion Criteria:

Subjects are eligible to be included in the study only if all the following criteria apply:

Subjects has provided informed consent prior to initiation of any study specific activities/procedures.

1. Age more than 21 to less than 85 years at signing of informed consent.
2. Diagnosis of heart failure, defined as requiring pharmacologic treatment for heart failure, with NYHA class I to class III at most recent screening assessment
3. Screening within 30 days after Clinic Visit or hospitalization for heart failure - either as a primary or secondary diagnosis.
4. History of (within the past 6 months) or current use of diuretics.
5. HF patient who is willing to comply with study restrictions including Everion device management (wearing and charging the device), Apple watch Series 4 and above device management (wearing and charging the device) and BiovitalsHF Patient App Management (pairing Everion device and Apple watch Series 4 and above and BiovitalsHF Patient App, and carrying the smartphone for answering questionnaires and data reporting)

Exclusion Criteria

Subjects are excluded from the study if any of the following criteria apply:

Disease Related

1. Acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina) stroke, or transient ischemic attack, major cardiac surgery, percutaneous coronary intervention, or valvuloplasty within the 30 days prior to screening.
2. Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) more than or equal to 180 mm Hg or diastolic BP (DBP)more than or equal to 110 mm Hg.
3. Untreated severe ventricular arrhythmia (e.g., ventricular tachycardia or ventricular fibrillation).
4. Symptomatic bradycardia or second or third-degree heart block without a pacemaker

Other Medical Conditions

1. Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in situ within the last 5 years
2. Hospitalization with any pathology that may meaningfully interfere with functional tolerance, cardiopulmonary capacity or mobility within the 30 days prior to screening.
3. Estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 or receiving dialysis at screening.

Prior/Concomitant Medication

1. Currently receiving treatment or procedure in another investigational device or drug study.

Other Exclusions

1. Likely to receive during the duration of the study, in the opinion of the investigator, planned revascularization, implantation of ICD or CRT, ventricular assist device, continuous or intermittent inotropic therapy, hospice care, or cardiac transplant.
2. Implantable cardioverter defibrillator or initiation of cardiac resynchronization therapy (CRT) (with/without implantable cardioverter defibrillator) within 30 days prior to enrollment.
3. Recipient of any major organ transplant (e.g. lung, liver, heart, bone marrow, kidney).
4. Less than 4 months prior Interventional Clinical Study participation.
5. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (e.g. Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
6. History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
7. Any individuals that are lacking the ability to consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of monitoring functional capacity among patients using mobile health monitoring platform	Measurement of correlation between physiology and accelerometer (activity) data/derivatives with: 6MWT; Patient-reported KCCQ; Lab results	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compliance rate	Compliance rate to measure the feasibility of collecting continuous, biometrics data and ePROs using mobile-health monitoring platform	8 weeks
Drop-out rate	Drop-out rate to measure the feasibility of collecting continuous, biometrics data and ePROs using mobile-health monitoring platform	8 weeks
Mean time worn/day	Mean time worn/day to measure the feasibility of collecting continuous, biometrics data and ePROs using mobile-health monitoring platform	8 weeks
Proportion of time worn that device produces reliable data	Proportion of time worn that device produces reliable data to measure the feasibility of collecting continuous, biometrics data and ePROs using mobile-health monitoring platform	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients on HF GDMT	Percentage of patients on beta blocker, ACE/ARN/ or ARNI and MRA	8 weeks
Percentage of patients on target dose of HF GDMT	Target dose of HF GDMT is according to 2021 Update to the 2017 ACC Expert Consensus Decision Pathway for Optimization of Heart Failure Treatment	8 weeks
Unplanned hospital visits of patients on HF GDMT and target dose of GDMT	30-days hospitalization, Clinic visits and ED visits, and its correlation to patients on HF GDMT and target dose of GDMT	8 weeks
Questionnaire for patient experience	Questionnaire to evaluate the subjects' experience with the mobile device(s) and mobile health monitoring platform	8 weeks
Association of ECG/Vitals/voice-related biomarker to progression of HF disease	Ability to detect changes in ECG/Vitals/voice biomarker, and correlate with functional status and clinical outcomes	8 weeks

Collaborators and Investigators

• Sponsor: Biofourmis Singapore Pte Ltd.
• Collaborators: Mayo Clinic; Food and Drug Administration (FDA)
• Investigators: Study Chair: Maulik Majmudar, M.D., Biofourmis Inc.

Publications and helpful links

General Publications

• Hsieh FY, Bloch DA, Larsen MD. A simple method of sample size calculation for linear and logistic regression. Stat Med. 1998 Jul 30;17(14):1623-34. doi: 10.1002/(sici)1097-0258(19980730)17:143.0.co;2-s.
• Palau P, Nunez E, Dominguez E, Sanchis J, Nunez J. Physical therapy in heart failure with preserved ejection fraction: A systematic review. Eur J Prev Cardiol. 2016 Jan;23(1):4-13. doi: 10.1177/2047487314562740. Epub 2014 Dec 8.
• Campbell RT, Jhund PS, Castagno D, Hawkins NM, Petrie MC, McMurray JJ. What have we learned about patients with heart failure and preserved ejection fraction from DIG-PEF, CHARM-preserved, and I-PRESERVE? J Am Coll Cardiol. 2012 Dec 11;60(23):2349-56. doi: 10.1016/j.jacc.2012.04.064. Epub 2012 Nov 7.
• Butler J, Hamo CE, Udelson JE, Pitt B, Yancy C, Shah SJ, Desvigne-Nickens P, Bernstein HS, Clark RL, Depre C, Dinh W, Hamer A, Kay-Mugford P, Kramer F, Lefkowitz M, Lewis K, Maya J, Maybaum S, Patel MJ, Pollack PS, Roessig L, Rotman S, Salsali A, Sims JJ, Senni M, Rosano G, Dunnmon P, Stockbridge N, Anker SD, Zile MR, Gheorghiade M. Exploring New Endpoints for Patients With Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2016 Nov;9(11):e003358. doi: 10.1161/CIRCHEARTFAILURE.116.003358.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2020
• Primary Completion (Actual): February 6, 2023
• Study Completion (Actual): February 6, 2023

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): October 5, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: wearable; accelerometer; 6MWT; biosensors
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CT003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No