PROACTIVE-HF IDE Trial Heart Failure NYHA Class III

Study Overview
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Brief Summary
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This is a prospective, open- label, single arm, multicenter clinical trial to evaluate the safety and effectiveness of the Cordella PA Sensor System in NYHA Class III Heart Failure Patients compared to a Performance Goal (PG).

Official Title
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A Prospective, Multi-Center, Open Label, Single Arm Clinical Trial Evaluating the Safety and Efficacy of the Cordella™ Pulmonary Artery Sensor System in NYHA Class III Heart Failure Patients (PROACTIVE- HF Trial)

Conditions
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Heart Failure NYHA Class III

Intervention / Treatment
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* Device: Cordella™ Pulmonary Artery Sensor System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject has given written informed consent Male or female, at least 18 years of age Diagnosis and treatment of HF (regardless of left ventricular ejection fraction (LVEF)) for ≥ 3 months and NYHA Class III HF at time of Screening Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines as standard-of-care for HF therapy in the United States, or current European Society of Cardiology (ESC) guidelines for HF treatment in Europe, with any intolerance documented. HF related hospitalization, HF treatment in a hospital day-care setting, or urgent outpatient clinic HF visit for IV diuretics within 12 month (last hospitalization should be 30 days before Screening/Enrollment) and/or N-terminal pro B-type Natriuretic Peptide (NT proBNP) at time of Screening/ Enrollment defined as: Subjects with LVEF ≤ 50%: NT-proBNP ≥ 1500 pg/mL. Subjects with LVEF > 50%: NT-proBNP ≥ 800 pg/mL . Thresholds for NT-proBNP (for both LVEF ≤ 50% and LVEF > 50%) will be corrected for body mass index (BMI) using a 4% reduction per BMI unit over 25 kg/m2 Subjects should be on diuretic therapy Subjects who are physically able to hold the myCordella™ Patient Reader unit (approximate weight 1.3lb) against the ventral thoracic surface for up to 2 minutes per day while in a seated position, as well as dock and undock the myCordella™ Patient Reader Subjects with sufficient eyesight, hearing, and mental capacity to respond to the myCordella™ Patient Reader's audio/visual cues and operate the myCordella™ Patient Reader Subject has sufficient Cellular and/ or Wi- Fi Internet coverage at home Subject agrees to return to the treating Investigator for all scheduled follow up visits and can return to the hospital for follow up Exclusion Criteria Intolerance to all neuro-hormonal antagonists (i.e., intolerance to ACE-I, ARB, ARNI, and beta-blockers) due to hypotension or renal dysfunction ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes) Subjects with history of recurrent pulmonary embolism ( ≥2 episodes within 5 years prior to Screening Visit) and/or deep vein thrombosis (< 3 month prior to Screening Visit) Subjects who have had a major cardiovascular (CV) event (e.g. myocardial infarction, stroke) within 3 months of the Screening Visit Unrepaired severe valvular disease Subjects with significant congenital heart disease that has not been repaired and would prevent implantation of the Cordella PA sensor or mechanical/tissue right heart valve(s) Subjects with known coagulation disorders Subjects with a hypersensitivity or allergy to platelet aggregation inhibitors including aspirin, clopidogrel, prasugrel, and ticagrelor; or patients unable to take dual antiplatelet or anticoagulants for one-month post implant Known history of life threatening allergy to contrast dye Subjects whereby RHC is contraindicated Subjects with an active infection at the Sensor Implant Visit Subjects with a Glomerular Filtration Rate (GFR) <25 ml/min or who are on chronic renal dialysis Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to screening visit Received or are likely to receive an advanced therapy (e.g. mechanical circulatory support or lung or heart transplant) in the next 12 months Subjects who are pregnant or breastfeeding Subjects who are unwilling or deemed by the Investigator to be unwilling to comply with the study protocol, or subjects with a history of non-compliance Severe illness, other than heart disease, which would limit survival to <1 year Subjects whose clinical condition, in the opinion of the Investigator, makes them an unsuitable candidate for the study Subjects enrolled in another investigational trial with an active treatment arm Subject who is in custody by order of an authority or a court of law

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Arm<br>Pulmonary Artery Pressure Guided Heart Failure Management (PAPGHFM) and Guideline Directed Medical Therapy (GDMT) considering daily Pulmonary Artery Pressure (PAP) measurements and vital signs collected by Cordella Heart Failure System (CHFS). | Device: Cordella™ Pulmonary Artery Sensor System<br>* The Cordella PA Sensor System (CorPASS) is intended to measure, record, and transmit pulmonary artery pressure (PAP) data from NYHA Class III heart failure patients at home to clinicians for assessment and patient-centered heart failure management and comprises of seven subsystems that operate together to take daily Pulmonary Artery Pressure (PAP) readings at a patient's home and transmit the results to a care provider for evaluation. Cordella Sensor Cordella Delivery System myCordella Patient Reader Reader Dock Cordella Calibration Equipment (CalEQ) myCordella Hub Cordella Data Analysis Platform (CDAP)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy 6 month incidence of HF related Hospitalizations (HFH) or all-cause mortality | 6 month incidence of HF related Hospitalizations (HFH) or all- cause mortality compared to a Performance Goal | 6 months | 
| Safety: Freedom from device/system related complication | Freedom from device/system related complication at 6 months | 6 months | 
| Safety: Freedom from pressure sensor failure | Freedom from pressure sensor failure at 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HF Hospitalizations | Number of HF Hospitalizations at 6 and 12 months post-implant compared to the number of HF Hospitalizations in the 6 and 12 months prior to implant | 6 months and 12 months | 
| HF Hospitalizations or Emergency Department/Hospital Outpatient IV diuretic visits. | Comparison of the number of HF Hospitalizations, Emergency Department/ Hospital Outpatient IV diuretic visits of Cohort #1 and Cohort #2 at 6 and 12 months post implant at 6 months, added together with equal weighting into a total number of events | 6 and 12 months | 
| Mortality | Cardiac and all-cause mortality | 3 years | 
| IV diuretic visits | Intravenous (IV) diuretic visits | 3 years | 
| Pulmonary Artery Pressure (PAP) | Change in PAP: a. From Baseline through 6 and 12 months in subjects with a baseline mPAP i. above target range ii. within or below target range iii. Overall b. Before and after 6-Minute Walk Test | 6 and 12 months | 
| Device success | Percentage of device success as documented by ability of the System to successfully transmit PAP data transmit PAP data | 3 years | 
| KCCQ | The Quality of Life KCCQ questionnaire is a measure of health-related quality of life. It is a 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life related to Heart Failure. Out of 23-items, 10 scores will be calculated: Physical Limitation, Symptom Stability, Symptom Frequency, Symptom Burden, Total Symptom Score, Self-Efficacy, Quality of Life, Social Limitation, Overall Summary Score, Clinical Summary Score .Presentation will be done by means of descriptive statistics including the absolute value and change from baseline by visit. | 3 years | 
| NYHA | Subjects complete a six (6) minute walk test at the study visits described in the study protocol. Total distance walked (meters) will be collected and analyzed by means of descriptive statistics including the absolute value and change from baseline by visit | 3 years | 
| NYHA and 6-Minute Walk Test | Functional status improvement, as measured by NYHA and 6-Minute Walk Test | 3 years | 
| Serious adverse events | Frequency of serious adverse events throughout the study | 3 years | 
| Incidence of HF Hospitalizations or all-cause mortality | Incidence of HF Hospitalizations or all-cause mortality at 12 months | 12 months | 
| N-terminal pro B-type Natriuretic Peptide (NT-proBNP | Change of N-terminal pro B-type Natriuretic Peptide (NT-proBNP) from Baseline through 6 and 12 months | 6 and 12 months | 
| Days Alive and Out of Hospital (DAOH) | Days Alive and Out of Hospital (DAOH) | 3 years | 
| Heart failure related Medication changes | Heart failure related Medication changes | 3 years | 
| HF Hospitalization or all-cause mortality | Incidence of HF Hospitalizations or all-cause mortality at 12 months | 12 months | 
| HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits, all-cause mortality | Combined outcome of: First and recurrent Heart Failure Hospitalizations Emergency Department / Hospital Outpatient IV diuretic visits all-cause mortality at 6 months, added together with equal weighting into a total number of events. | 6 months | 
| HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits | HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits at 6 and 12 months | 6 and 12 months | 
| Implant procedure and procedure related adverse events and serious adverse events | Frequency of implant procedure and procedure related adverse events and serious adverse events | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Heart Disease, Cardiovascular Disease, Pulmonary Artery Pressure