REALIsM-HF Pilot Study

Not Applicable

Completed

• Conditions: Heart Failure
• Interventions: Device: AVIVO Mobile Patient Management (MPM) System; Device: VitalPatch biosensor; Device: DynaPort Move Monitor

• Registration Number: NCT03507439
• Lead Sponsor: Bayer

Brief Summary

The study aims to explore two marketed devices providing a multimarker monitoring including physical activity under real-life conditions in patients with heart failure with preserved ejection fraction (HFpEF) and with heart failure and reduced ejection fraction (HFrEF). It aims to identify potential novel endpoints for future heart failure trials by exploring clinically relevant changes over time and correlations/associations with conventional endpoints such as the six minute walking distance (6MWD), biomarkers and clinical events. Furthermore, it aims to address the challenges and feasibility of implementing device based measurements under real-life conditions.

Detailed Description

Device 1 AVIVO Mobile Patient Management System (Medtronic USA), substituted by VitalPatch biosensor (VitalConnect USA) during the course of the study Device 2 DynaPort Move Monitor (McRoberts, NL)

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study Start: 2018-04-06
• Study First Submitted: 2018-04-20
• Study First Submitted QC: 2018-04-20
• Study First Posted: 2018-04-25
• Primary Completion: 2020-12-30
• Study Completion: 2021-03-12
• Results First Submitted: 2022-03-14
• Status Verified: 2022-07
• Results First Submitted QC: 2022-07-29
• Last Update Submitted: 2022-07-29
• Results First Posted: 2023-07-03
• Last Update Posted: 2023-07-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 27

Inclusion Criteria

• Written informed consent signed before any study-specific procedure
• Men or women aged 45 years and older
• Established diagnosis of chronic heart failure NYHA class II-IV
• Worsening heart failure requiring hospitalization for the initiation of intensification of heart failure therapy with at least one of the following: a) BNP ≥ 100 pg/mL or NT-proBNP ≥ 400 pg/mL (sinus rhythm) OR BNP ≥ 300 pg/mL or NT-proBNP ≥ 1200 pg/mL (atrial fibrillation); OR b) Radiographic evidence of pulmonary congestion (interstitial edema, pulmonary venous hypertension, vascular congestion, pleural effusion); OR c) Catheterization documented elevated filling pressures at rest (left ventricular end-diastolic pressure ≥15 mmHg or pulmonary capillary wedge pressure ≥ 20 mmHg) or with exercise (pulmonary capillary wedge pressure ≥ 25 mmHg) OR Ambulatory patients with a history of heart failure on individually optimized treatment with HF medications unless contraindicated or not tolerated, for at least 12 weeks and at least one of the following: a) Hospitalization for heart failure within the past 12 months; OR b) BNP ≥ 100 pg/mL or NT-proBNP ≥ 400 pg/mL (sinus rhythm) or BNP ≥ 300 pg/mL or NT-proBNP ≥ 1200 pg/mL (atrial fibrillation)
• For HFrEF only: EF ≤35% assessed by any imaging modality (e.g. echocardiography, cardiac magnetic resonance, cine levocardiography) within 12 months prior to study inclusion
• For HFpEF only: EF ≥45% assessed by any imaging modality (e.g. echocardiography, cardiac magnetic resonance, cine levocardiography) within 12 months prior to study inclusion
• Willingness to wear the DynaPort Move Monitor accelerometer belt and VitalPatch Biosensor during the trial
• Body size allows wearing of the accelerometer belt as confirmed by ability to comfortably fasten the test belt provided for the screening process

Exclusion Criteria

• Inability to comply with planned study procedures or to comply with study protocol requirements; this includes completing required data collection, and attending required follow up study visits
• Hemoglobin < 8.0 g/dl
• Acute coronary syndrome or percutaneous coronary intervention within 3 months prior to informed consent
• Listing for heart transplantation and / or anticipated implantation of a ventricular assist device
• Inability to exercise: wheelchair / scooter / walker dependent; dependent on supplemental oxygen
• Known clinically significant persistent coronary ischemia (based on medical history, a preexisting or a recent clinical stress test)
• HF is not the primary factor limiting activity within the last three months as indicated by the patient affirming #1, #2 or #3 of the following questionnaire: My ability to be active is most limited by: #1 - Joint, foot, leg, hip or back pain; #2 - Unsteadiness or dizziness impairing daily mobility; #3 - Lifestyle, weather, or I just don't like to be active
• Occurrence of any of the following within 3 months prior to informed consent: Myocardial infarction, Hospitalization for unstable angina, Stroke or transient ischemic attack, Coronary artery bypass graft (CABG), Percutaneous coronary intervention (PCI), Implantation of a cardiac resynchronization therapy device (CRTD), Major surgery (that could interfere with patients' ability to exercise)
• PCI, CABG or implantation of a CRTD planned between randomization and Visit 4
• Subject who cannot tolerate placement of external patch monitor on chest in the proposed location (ECG lead II orientation)
• Subject with known allergies or hypersensitivities to adhesives or hydrogels
• Severe uncorrected valvular heart disease
• Known clinically relevant ventricular arrhythmias (sustained ventricular tachycardia, ventricular flutter or fibrillation)
• Severe pulmonary disease with any of the following: Requirement of continuous (home) oxygen or History of chronic obstructive pulmonary disease ≥ GOLD III
• Previous (within 30 days or 5 half-lives of the investigational drug, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s) or device(s)
• Any condition or therapy, which would make the patient unsuitable for the study, or life expectancy less than 12 months (e.g. active malignancy)
• Heavy alcohol consumption or the use of illicit drugs that, in the opinion of the investigator, may interfere with the patient's safety and / or compliance
• Patients who regularly (> 1x per week) swim, do water aerobics or go to the sauna, unwilling to omit this activity while needing to wear the study specific medical devices
• Active myocarditis
• Primary hypertrophic cardiomyopathy
• Constrictive pericarditis or pericardial tamponade
• Close affiliation with the investigational site, e.g. a close relative of the investigator, dependent person (e.g. employee or student of the investigational site)
• Previous participate in the study

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HFrEF	DynaPort Move Monitor	Participants with established diagnosis of heart failure with reduced ejection fraction (HFrEF; EF ≤ 35%) wore the AVIVO MPM System or VitalPatch biosensor for 5 monitoring periods with patches applied on Day 0, 9, 16, 77 and 84; and the DynaPort Move Monitor belt for 2 monitoring periods with belts applied on Day 9 and Day 77.
HFrEF	VitalPatch biosensor	Participants with established diagnosis of heart failure with reduced ejection fraction (HFrEF; EF ≤ 35%) wore the AVIVO MPM System or VitalPatch biosensor for 5 monitoring periods with patches applied on Day 0, 9, 16, 77 and 84; and the DynaPort Move Monitor belt for 2 monitoring periods with belts applied on Day 9 and Day 77.
HFpEF	VitalPatch biosensor	Participants with established diagnosis of heart failure with preserved ejection fraction (HFpEF; EF ≥ 45%) wore the AVIVO MPM System or VitalPatch biosensor for 5 monitoring periods with patches applied on Day 0, 9, 16, 77 and 84; and the DynaPort Move Monitor belt for 2 monitoring periods with belts applied on Day 9 and Day 77.
HFrEF	AVIVO Mobile Patient Management (MPM) System	Participants with established diagnosis of heart failure with reduced ejection fraction (HFrEF; EF ≤ 35%) wore the AVIVO MPM System or VitalPatch biosensor for 5 monitoring periods with patches applied on Day 0, 9, 16, 77 and 84; and the DynaPort Move Monitor belt for 2 monitoring periods with belts applied on Day 9 and Day 77.
HFpEF	AVIVO Mobile Patient Management (MPM) System	Participants with established diagnosis of heart failure with preserved ejection fraction (HFpEF; EF ≥ 45%) wore the AVIVO MPM System or VitalPatch biosensor for 5 monitoring periods with patches applied on Day 0, 9, 16, 77 and 84; and the DynaPort Move Monitor belt for 2 monitoring periods with belts applied on Day 9 and Day 77.
HFpEF	DynaPort Move Monitor	Participants with established diagnosis of heart failure with preserved ejection fraction (HFpEF; EF ≥ 45%) wore the AVIVO MPM System or VitalPatch biosensor for 5 monitoring periods with patches applied on Day 0, 9, 16, 77 and 84; and the DynaPort Move Monitor belt for 2 monitoring periods with belts applied on Day 9 and Day 77.

Primary Outcome Measures

Name	Time	Method
Daily Steps Count	At Day 9 and Day 77	Daily steps count was measured with DynaPort Move Monitor device and evaluated to reflect the amount of daily physical activity.
Duration of Daily Physical Activity	At Day 9 and Day 77	Duration of daily physical activity was measured with DynaPort Move Monitor device.
Daily Physical Activity Level	At Day 9 and Day 77	Movement intensity of an activity, which was the average body acceleration (g) during this activity, was measured with DynaPort Move Monitor device and evaluated as daily physical activity level (PAL). Higher values indicate higher physical activity level and intensity.
Duration of Daily Physical Activity Measured With VitalPatch Biosensor	Up to Day 84	Duration of daily physical activity was collected and measured with VitalPatch biosensor.
Total Daily Energy Expenditure	At Day 9 and Day 77	Total daily energy expenditure was measured with DynaPort Move Monitor device and evaluated to reflect the amount of daily physical activity.
Time Duration Per Activity Status	At Day 9 and Day 77	Time duration per activity status was measured with DynaPort Move Monitor device and evaluated to reflect the intensity of daily physical activity. Physical Activity intensities use absolute aerobic intensity in terms of Metabolic Equivalent of Task (MET), which is a physiological concept expressing the energy cost of a physical activity as a multiple of Basal Metabolic Rate (BMR). By convention, 1 MET is considered as the resting metabolic rate obtained during quiet sitting. According to the American College of Sports Medicine (ACSM) thresholds for adults: Light-intensity activities are defined as 1.1 MET to 2.9 METs; Moderate-intensity activities are defined as 3.0 to 5.9 METs; Vigorous-intensity activities are defined as 6.0 METs or more.
Amount of Daily Physical Activity Measured With VitalPatch Biosensor	Up to Day 84	Amount of daily physical activity was collected and measured with VitalPatch biosensor.
Intensity of Daily Physical Activity Measured With VitalPatch Biosensor	Up to Day 84	Intensity of daily physical activity was collected and measured with VitalPatch biosensor.

Secondary Outcome Measures

Name	Time	Method
Sleep Movements	Up to Day 84	Sleep movements was measured with DynaPort Move Monitor device.
Sleep Patterns	Up to Day 84	Sleep patterns was measured with DynaPort Move Monitor device.
Growth Differentiation Factor 15 (GDF 15)	At Day 9 and Day 84	Blood sample for biomarkers including GDF 15 were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls.
Left Ventricular Ejection Fraction	At Day 84	Left ventricular ejection fraction was measured by echocardiography.
Left Atrial End Systolic Volume Index	At Day 84	Left atrial end systolic volume index was measured by echocardiography.
Tricuspid Annular Plane Systolic Excursion	At Day 84	Tricuspid annular plane systolic excursion was measured by echocardiography.
6-minute Walking Distance (6MWD)	At Day 84	6-minute walking distance (6MWD) is a exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. An increase in the distance walked indicates improvement in basic mobility.
Galectin-3	At Day 9 and Day 84	Blood sample for biomarkers including Galectin-3 were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls.
Quality of Life as Measured With the Kansas City Cardiomyopathy Questionnaire Score	At Day 9 and Day 84	The Kansas City Cardiomyopathy Questionnaire (KCCQ) is the leading health-related quality-of-life measure for patients with heart failure (HF). It is a 23-item questionnaire that independently measures the impact of patients' HF, or its treatment, on 7 distinct domains: symptom frequency, symptom burden, physical limitation, quality of life, social limitations, self-efficacy and symptoms stability. Physical Limitation ranges 0-100. Total Symptom Score (range 0-100) combines the Symptom Frequency and the Symptom Burden scores; Clinical Summary Score (range 0-100) combines the Total Symptom and Physical Limitation scores to replicate the NYHA classification; Overall Summary Score (range 0-100) includes the Total Symptom, Physical Limitation, Social Limitations, and Quality of Life scores. Higher scores indicate more favorable states.
Sit-to-stand Behaviour	Up to Day 84	Sit-to-stand behaviour was measured with DynaPort Move Monitor device.
Quality of Life as Measured With the PRO - Activity Scores	At Day 9 and Day 77	REALIsM-HF exploratory daily questionnaire was developed to include patient-reported outcome (PRO) items that can be administered as a daily diary in the study. Overall activity score ranges from 0 to 240 and general physical activity score ranges from 0 to 4. Higher scores indicate more favorable states.
Human Interleukin-1 Receptor 4 / ST2 (sST2)	At Day 9 and Day 84	Blood sample for biomarkers including sST2 were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls. Values above upper limit of quantification (ULOQ) were substituted by ULOQ for the calculation of statistics (ULOQ = 80.0)
Human Insulin-like Growth Factor Binding (IGFBP7)	At Day 9 and Day 84	Blood sample for biomarkers including IGFBP7 were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls.
Left Ventricular End-diastolic Volume	At Day 84	Left ventricular end-diastolic volume was measured by echocardiography.
Left Atrial End-systolic Volume	At Day 84	Left atrial end-systolic volume was measured by echocardiography.
Mitral Septal Annulus Early Diastolic Peak Velocity	At Day 84	Mitral septal annulus early diastolic peak velocity was measured by echocardiography.
Heart Rate Variability (HRV) Derived From ECG	Up to Day 84	Heart rate variability (HRV) derived from ECG were measured with AVIVO MPM and VitalPatch biosensor
Number of Participants Per NYHA Classification by Visit	At Day 9 and Day 84	The New York Heart Association (NYHA) Classification provides a simple way of classifying the extent of heart failure. The Stages of Heart Failure: Class I = No symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. Class II = Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III = Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20 - 100 m). Comfortable only at rest. Class IV = Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.
Mitral Peak Velocity of Early Filling (E)	At Day 84	Mitral peak velocity of early filling (E) was measured by echocardiography.
Quality of Life as Measured With the PRO - Change in Activities and Symptoms	At Day 9 and Day 77	REALIsM-HF exploratory daily questionnaire was developed to include patient-reported outcome (PRO) items that can be administered as a daily diary in the study. Answers to question "How have your physical activities changed since you were discharged from the hospital": 1= Very much more physically active; 2= Much more physically active; 3= A little more physically active; 4= No change in physical activities; 5= A little less physically active; 6= Much less physically active; 7= Very much less physically active. Answers to questions "How has your feeling of tiredness changed since you were discharged from the hospital", "How has your shortness of breath changed since you were discharged from the hospital" and "How has your swelling in your legs, ankles, or feet changed since you were discharged from the hospital": 1= Very much improved; 2= Much improved; 3= Minimally improved; 4= No change; 5= Minimally worse; 6= Much worse; 7= Very much worse.
Copeptin	At Day 9 and Day 84	Blood sample for biomarkers including Copeptin were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls.
Mitral Lateral Annulus Early Diastolic Peak Velocity	At Day 84	Mitral lateral annulus early diastolic peak velocity was measured by echocardiography.
N-terminal Propeptide of BNP (NT-proBNP)	At Day 9 and Day 84	Blood sample for biomarkers including NT-proBNP were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls.
High Sensitive Troponin T (hsTRT)	At Day 9 and Day 84	Blood sample for biomarkers including hsTRT were collected from participants in order to validate such biomarkers for clinical use in the context of heart failure. Biomarkers concentration was determined in plasma/serum by a central laboratory using validated assays platforms including appropriate quality controls. Values below lower limit of quantification (LLOQ) were substituted by 1/2 LLOQ for the calculation of statistics (LLOQ = 13.0)
Blood Pressure	At Day 9, Day 77 and Day 84	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were collected.
Heart Rate	At Day 9, Day 77 and Day 84	Heart rate data were collected by electrocardiogram (ECG).
Interventricular Septal Wall Thickness	At Day 84	Interventricular septal wall thickness was measured by echocardiography.
Diameter of the Left Ventricle in Diastole	At Day 84	Diameter of the left ventricle in diastole was measured by echocardiography.
Diameter of the Left Ventricle in Systole	At Day 84	Diameter of the left ventricle in systole was measured by echocardiography.
Mitral Peak Velocity of Late Filling (A)	At Day 84	Mitral peak velocity of late filling (A) was measured by echocardiography.
Pressure Gradient of Tricuspid Valve	At Day 84	Pressure gradient of tricuspid valve was measured by echocardiography.
Right Atrial Mean Pressure	At Day 84	Right atrial mean pressure was measured by echocardiography.
Left Ventricular End-systolic Volume	At Day 84	Left ventricular end-systolic volume was measured by echocardiography.

Trial Locations

Locations (5)

Heinrich-Heine-Universität Düsseldorf; 🇩🇪 Düsseldorf, Nordrhein-Westfalen, Germany

Northwestern University Feinberg School of Medicine; 🇺🇸 Chicago, Illinois, United States

Universitätsklinikum Köln; 🇩🇪 Köln, Nordrhein-Westfalen, Germany

Charité - Campus Virchow-Klinikum (CVK); 🇩🇪 Berlin, Germany

ASST Spedali Civili di Brescia; 🇮🇹 Brescia, Lombardia, Italy