PROACTIVE-HF-2 Trial Heart Failure NYHA Class II and III

Study Overview
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Brief Summary
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This is a prospective, multi-center, open label, randomized control clinical trial evaluating the safety and efficacy of the Cordella™ Pulmonary Artery Sensor System in NYHA Class II-III Heart Failure Patients (PROACTIVE-HF-2 Trial). The study contains of 5 arms: Randomized Arm - To demonstrate safety and efficacy of the Cordella PA Sensor System in NYHA Class II HF patients. Treatment Arm (Cohort 1) Active Control Arm (Cohort 2) Crossover Arm (Cohort 3) Single Arm - To demonstrate safety and efficacy of the Cordella PA Sensor System linked with a clinician-directed patient self-management strategy in NYHA Class III HF patients. Clinician-Directed Patient Self-Management Arm (Cohort 4) Clinician Management Arm (Cohort 5)

Official Title
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A Prospective, Multi-Center, Open Label, Randomized Control Clinical Trial Evaluating the Safety and Efficacy of the Cordella™ Pulmonary Artery Sensor System in New York Heart Association (NYHA) Class II-III Heart Failure Patients

Conditions
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Heart Failure NYHA Class II, 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 LVEF) for ≥ 3 months and NYHA Class II HF (Randomized Arm) or NYHA III (Single Arm) at time of Screening Subjects should be receiving appropriate medical therapy for heart failure according to current AHA/ACC guidelines as standard-of-care for HF therapy in the United States, or current ESC guidelines for HF treatment in Europe for at least 30 days prior to the Screening/Enrollment visit. Stable is defined as no more than a 100% increase or 50% decrease in dose. These criteria may be waived if a subject is intolerant of ACE-I, ARB, ARNI), MRA, beta-blockers, or SGLT2i, subject is unable to afford these agents, subject has contraindications to these agents, or these agents are not indicated under the Guidelines. Such intolerance, lack of affordability, contraindications, or lack of indications must be documented. HFrEF (EF < 50%): Subject has been on stable medications maximized to the subject's tolerance of ACE-I or ARB or ARNI, MRA, beta-blockers, and SGLT2i as determined by the study investigator for at least 30 days prior to randomization HFpEF (EF ≥ 50%): Subject has been on stable medication maximized to the subject's tolerance of SGLT2i as determined by the study investigator for at least 30 days prior to randomization Randomized Arm- HF related hospitalization or urgent HF visit within 6 months (last hospitalization should be 30 days before Screening /Enrollment) 5. Single Arm-HF related hospitalization or urgent HF visit 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 ≥ 1000 pg/mL. Subjects with LVEF > 50%: NT-proBNP ≥ 700 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 6. Subjects should be on diuretic therapy (≥40 mg] furosemide or equivalent) for ≥ 1 month at time of Screening 7. 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 8. 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 9. Subject has sufficient Cellular and/ or Wi- Fi Internet coverage at home 10. 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: ACC/AHA Stage D refractory HF (including a known history of >24 hours of IV inotropic therapy to support circulation within the past 6 months (other than relation to a procedure)) Subjects with history of recurrent pulmonary embolism (≥2 episodes within 5 years prior to Screening Visit) and/or deep vein thrombosis in the femoral or IJ vein used for access (< 3 month prior to Screening Visit) Subjects with a resting systolic blood pressure <90 mmHg and/ or severe pre-capillary pulmonary hypertension with a pulmonary artery systolic pressure of ≥70 mm/Hg with pulmonary capillary wedge pressure ≤ 15 mmHg at the Cordella PA Sensor Implant RHC (V2) 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 Cordella Sensor Implant Visit Subjects with a GFR <20 ml/min or who are on chronic renal dialysis Implanted with Cardiac Resynchronization Therapy-Pacemaker (CRT-P) or Cardiac Resynchronization Therapy-Defibrillator (CRT-D), or having undergone mitral/tricuspid valve repair/replacement within 90 days or catheter ablation for atrial fibrillation within 30 days prior to screening visit Received or are likely to receive an advanced therapy (e.g., durable mechanical circulatory support or lung or heart transplant) in the next 24 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 <2 years 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Randomized Arm- Treatment Arm<br>All subjects will receive the Cordella Sensor. Clinicians will manage the subjects to target PAP per protocols specific Treatment Guidelines and according to Guideline-Directed Medical Therapy. | 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, with the goal of reducing heart failure hospitalizations. The system 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 Tablet Cordella Data Analysis Platform (CDAP)<br>|
| Experimental: Randomized Arm- Active Control Arm<br>All subjects will receive the Cordella Sensor. Clinicians will manage subjects using the subjects daily data trends (BP, weight, HR, SpO2 symptoms) according to Guideline Directed Medical Therapy. | 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, with the goal of reducing heart failure hospitalizations. The system 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 Tablet Cordella Data Analysis Platform (CDAP)<br>|
| Experimental: Randomized Arm- Crossover Arm<br>All subjects will receive the Cordella Sensor. At least 12 months following implant and following an adjudicated HFH, subjects in the Active Control Arm can qualify to crossover to the Crossover Arm and both patients and clinicians would then be unmasked to PAP. Clinicians will then manage the subjects to target PAP per protocols specific Treatment Guidelines and according to Guideline-Directed Medical Therapy. | 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, with the goal of reducing heart failure hospitalizations. The system 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 Tablet Cordella Data Analysis Platform (CDAP)<br>|
| Experimental: Single Arm- Clinician-Directed Patient Self-Management Arm<br>All subjects will receive the Cordella Sensor. Subjects will self-manage their Loop diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines and Clinicians will manage the patients according to Guideline-Directed Medical Therapy. | 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, with the goal of reducing heart failure hospitalizations. The system 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 Tablet Cordella Data Analysis Platform (CDAP)<br>|
| Experimental: Single Arm- Clinician Management Arm<br>All subjects will receive the Cordella Sensor. Clinicians will manage the subjects to target PAP per protocols specific Treatment Guidelines and according to Guideline-Directed Medical Therapy. | 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, with the goal of reducing heart failure hospitalizations. The system 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 Tablet 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- Randomized Arm - A composite of first HF event or death from Cardiovascular Death up to 24 months. | A composite endpoint of first HF event or death from CVD up to 24 months. | 24 months | 
| Efficacy- Single Arm- 12 month incidence of HF related Hospitalizations (HFH) or all-cause mortality | 12 month incidence of HF related Hospitalizations (HFH) or all-cause mortality compared to a Performance Goal | 12 months | 
| Safety- Randomized Arm- Freedom from device/system related complication | Freedom from device/system related complication at 24 months | 24 months | 
| Safety- Randomized Arm-Freedom from pressure sensor failure | Freedom from pressure sensor failure at 24 months | 24 months | 
| Safety- Single Arm-Freedom from device/system related complication | Freedom from device/system related complication at 12 months | 12 months | 
| Safety- Single Arm- Freedom from pressure sensor failure | Freedom from pressure sensor failure at 12 months | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy - Randomized and Single Arm- HF Hospitalizations | -Incidence of HFH at 12, 18, and 24 months | 12 months, 18 months and 24 months | 
| Efficacy - Randomized and Single Arm- HF Hospitalizations | -Number of HFH at 12- and 24-months post-implant compared to the number of HFH in the 12 and 24 months prior to implant | 12 months and 24 months | 
| Efficacy -Randomized and Single Arm - HF Hospitalizations | Combined outcome of : First and recurrent HF Hospitalizations Urgent HF Visits all-cause mortality | 12 month | 
| Efficacy -Randomized and Single Arm - HF Hospitalizations | Length of stay | Duration of study | 
| Efficacy -Randomized and Single Arm - All-cause mortality | All-cause mortality | Duration of study | 
| Efficacy -Randomized and Single Arm - Death from cardiovascular disease | Death from cardiovascular disease | Duration of study | 
| Efficacy -Randomized and Single Arm - Urgent HF visits | Urgent HF visits | Duration of study | 
| Efficacy - Randomized Arm - Incidence of HF hospitalizations or all-cause mortality | Incidence of HF hospitalizations or all-cause mortality | 12 months | 
| Efficacy - Single Arm - Composite of first HF event (HF hospitalization or urgent HF visit or death from cardiovascular disease (CVD) | Composite of first HF event (HF hospitalization or urgent HF visit or | Up to 24 months | 
| Eff-Rando and SA -time to death, # HFH or urgent HF visits, time to first HFH or urgent HF visit, diff >/= 15 KCCQ BSL to 24 mos,diff >/= 10 in KCCQ BSL to 24 mos, diff >/= 5 in KCCQ BSL to 24 mos, diff >/= 30m in 6 MWT BSL to 24 mos | -time to death, # HFH or urgent HF visits, time to first HFH or urgent HF visit, diff >/= 15 KCCQ BSL to 24 mos,diff >/= 10 in KCCQ BSL to 24 mos, diff >/= 5 in KCCQ BSL to 24 mos, diff >/= 30m in 6 MWT BSL to 24 mos | Duration of study | 
| Efficacy - Randomized and SIngle Arm - Various measurements via ECHO and evaluated by ECHO core lab at Baseline, 12, 24, 36, 48 and 60 months. | Various measurements via ECHO and evaluated by ECHO core lab at Baseline, 12, 24, 36, 48 and 60 months. | Duration of study | 
| Efficacy - Randomized and Single Arm - Heart failure related medication changes | Heart failure related medication changes | Duration of study | 
| Efficacy - Randomized and Single Arm - Change in PAP from baseline | Change in PAP from baseline | Duration of study | 
| Efficacy - Randomized and Single Arm - Change in PAP from baseline as measured by echocardiogram (ECHO) and evaluated by an ECHO core lab at 12, 24, 36, 48, and 60 months | Change in PAP from baseline as measured by echocardiogram (ECHO) and evaluated by an ECHO core lab at 12, 24, 36, 48, and 60 months | Duration of study | 
| Efficacy - Randomized and Single Arm - Patient Outcome Measures as measured by KCCQ, Brief Illness Perception Questionnaire, and EuroQol-5 Dimensions-5 Level (EQ-5D-5L) | Patient Outcome Measures as measured by KCCQ, Brief Illness Perception Questionnaire, and EuroQol-5 Dimensions-5 Level (EQ-5D-5L) | Duration of study | 
| Efficacy - Randomized and Single Arm - Functional status improvement as measured by NYHA classification and 6MWT | Functional status improvement as measured by NYHA classification and 6MWT | Duration of study | 
| Efficacy - Randomized and Single Arm - HFH stratified by ejection fraction (HFrEF, HFmrEF, HFpEF, and HF recovered EF) and baseline enrollment ECHO estimated systolic PAP | HFH stratified by ejection fraction (HFrEF, | Duration of study | 
| Efficacy - Randomized and Single Arm - Mortality by baseline EF (HFrEF, HFmrEF, HFpEF, HF recovered EF), and baseline enrollment ECHO estimated systolic PAP | Mortality by baseline EF (HFrEF, HFmrEF, | Duration of study | 
| Efficacy - Randomized and Single Arm - Days alive outside hospital (DAOH) | Days alive outside hospital (DAOH) | Duration of study | 
| Efficacy - Randomized and Single Arm - Health Economic Analysis | Health Economic Analysis | Duration of study | 
| Efficacy - Randomized and Single Arm - Adherence to regular PAP and vital sign measurements including a sub-analysis on subjects who move to another area of the country | Adherence to regular PAP and vital sign measurements including a sub-analysis on subjects who move to another area of the country | Duration of study | 
| Safety - Randomized Arm - Freedom from device/system related complications at 12 months | Freedom from device/system related complications at 12 months | Duration of study | 
| Safety - Randomized Arm - Freedom from pressure sensor failure at 12 months | Freedom from pressure sensor failure at 12 months | Duration of study | 
| Safety - Randomized and Single Arm - Pressure sensor failure rate throughout the study | Pressure sensor failure rate throughout the study | Duration of study | 
| Safety - Randomized and Single Arm - Frequency of serious adverse events throughout the study | Frequency of serious adverse events throughout the study | Duration of study | 
| Safety - Randomized and Single Arm - Frequency of implant procedure and procedure related adverse events and serious adverse events | Frequency of implant procedure and procedure related adverse events and serious adverse events | Duration of study | 
| Safety - Single Arm - Freedom from device/system related complications at 24 months | Freedom from device/system related complications at 24 months | Duration of study | 
| Safety - Single Arm - Freedom from pressure sensor failure at 24 months | Freedom from pressure sensor failure at 24 months | Duration of study | 

 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