Clinical trial NCT03507439: REALIsM-HF Pilot Study
Official title: Real Life Multimarker Monitoring in Patients With Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Heart failure with preserved ejection fraction (HFpEF)
Heart failure with reduced ejection fraction (HFrEF)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2018-04-25
Enrollment: 27
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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)

Eligibility criteria: 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

Primary outcomes:
measure: Daily Steps Count
timeFrame: At Day 9 and Day 77
measure: Daily Physical Activity Level
timeFrame: At Day 9 and Day 77
measure: Total Daily Energy Expenditure
timeFrame: At Day 9 and Day 77
measure: Duration of Daily Physical Activity
timeFrame: At Day 9 and Day 77
measure: Time Duration Per Activity Status
timeFrame: At Day 9 and Day 77
measure: Amount of Daily Physical Activity Measured With VitalPatch Biosensor
timeFrame: Up to Day 84
measure: Duration of Daily Physical Activity Measured With VitalPatch Biosensor
timeFrame: Up to Day 84
measure: Intensity of Daily Physical Activity Measured With VitalPatch Biosensor
timeFrame: Up to Day 84
Secondary outcomes:
measure: 6-minute Walking Distance (6MWD)
timeFrame: At Day 84
measure: Sleep Movements
timeFrame: Up to Day 84
measure: Sleep Patterns
timeFrame: Up to Day 84
measure: Sit-to-stand Behaviour
timeFrame: Up to Day 84
measure: Quality of Life as Measured With the Kansas City Cardiomyopathy Questionnaire Score
timeFrame: At Day 9 and Day 84
measure: Quality of Life as Measured With the PRO - Activity Scores
timeFrame: At Day 9 and Day 77
measure: Quality of Life as Measured With the PRO - Change in Activities and Symptoms
timeFrame: At Day 9 and Day 77
measure: Copeptin
timeFrame: At Day 9 and Day 84
measure: Galectin-3
timeFrame: At Day 9 and Day 84
measure: Growth Differentiation Factor 15 (GDF 15)
timeFrame: At Day 9 and Day 84
measure: Human Interleukin-1 Receptor 4 / ST2 (sST2)
timeFrame: At Day 9 and Day 84
measure: Human Insulin-like Growth Factor Binding (IGFBP7)
timeFrame: At Day 9 and Day 84
measure: N-terminal Propeptide of BNP (NT-proBNP)
timeFrame: At Day 9 and Day 84
measure: High Sensitive Troponin T (hsTRT)
timeFrame: At Day 9 and Day 84
measure: Blood Pressure
timeFrame: At Day 9, Day 77 and Day 84
measure: Heart Rate
timeFrame: At Day 9, Day 77 and Day 84
measure: Interventricular Septal Wall Thickness
timeFrame: At Day 84
measure: Diameter of the Left Ventricle in Diastole
timeFrame: At Day 84
measure: Diameter of the Left Ventricle in Systole
timeFrame: At Day 84
measure: Left Ventricular End-diastolic Volume
timeFrame: At Day 84
measure: Left Ventricular End-systolic Volume
timeFrame: At Day 84
measure: Left Ventricular Ejection Fraction
timeFrame: At Day 84
measure: Left Atrial End-systolic Volume
timeFrame: At Day 84
measure: Left Atrial End Systolic Volume Index
timeFrame: At Day 84
measure: Mitral Peak Velocity of Early Filling (E)
timeFrame: At Day 84
measure: Mitral Peak Velocity of Late Filling (A)
timeFrame: At Day 84
measure: Mitral Lateral Annulus Early Diastolic Peak Velocity
timeFrame: At Day 84
measure: Mitral Septal Annulus Early Diastolic Peak Velocity
timeFrame: At Day 84
measure: Tricuspid Annular Plane Systolic Excursion
timeFrame: At Day 84
measure: Pressure Gradient of Tricuspid Valve
timeFrame: At Day 84
measure: Right Atrial Mean Pressure
timeFrame: At Day 84
measure: Heart Rate Variability (HRV) Derived From ECG
timeFrame: Up to Day 84
measure: Number of Participants Per NYHA Classification by Visit
timeFrame: At Day 9 and Day 84
Other outcomes:
measure: Number of Participants With Adverse Events
timeFrame: From signing the ICF until follow-up visit (up to 7 months)
Locations:
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Düsseldorf
country: Germany
facility: Heinrich-Heine-Universität Düsseldorf
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Universitätsklinikum Köln
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Charité - Campus Virchow-Klinikum (CVK)
city: Brescia
country: Italy
facility: ASST Spedali Civili di Brescia
state: Lombardia
Study officials:
References: