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

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

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:

NYHA II Cohort - To demonstrate safety and efficacy of the Cordella PA Sensor System in NYHA Class II HF patients, where patients have daily access to PAP data.

• Treatment Arm (Group 1)
• Active Control Arm (Group 2)
• Crossover Arm (Group 3)

NYHA III Cohort - To demonstrate safety and efficacy of the Cordella PA Sensor System in NYHA Class III HF patients, where patients have daily access to PAP data, including a randomized sub-study to evaluate a clinician-directed patient self-management strategy.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Heart Failure NYHA Class II; Heart Failure NYHA Class III
• Intervention / Treatment: Device: Cordella™ Pulmonary Artery Sensor System

• Study Type: Interventional
• Enrollment (Estimated): 1750
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrea Sauerland; Phone Number: (630) 473-3200; Email: clinical@endotronix.com

Study Locations

• Belgium
  • Brussels, Belgium
    • Not yet recruiting
    • UZ Brussel
    • Contact: Evelyne Wirix; Phone Number: +32 2 477 41 11; Email: evelyne.wirix@uzbrussel.be
    • Principal Investigator: Frederik Verbrugge
  • Aalst
    • Aalst, Aalst, Belgium, 9300
      • Active, not recruiting
      • AZORG Aalst
• Ireland
  • Galway, Ireland
    • Not yet recruiting
    • University Hospital Galway
    • Contact: Eileen Coen; Phone Number: +353 91 524 222; Email: eileen.coen@nuigalway.ie
    • Principal Investigator: Faisal Sharif
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Recruiting
      • St. Joseph's Hospital and Medical Center
      • Contact: Namit Rohant, MD
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • USC
      • Contact: Aaron Wolfson
      • Principal Investigator: Aaron Wolfson
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Medical Center
      • Contact: Mark Lacsamana
      • Principal Investigator: Shweta Motiwala, MD
  • Florida
    • Miami, Florida, United States, 33176
      • Recruiting
      • Baptist Health South Florida
      • Principal Investigator: Sandra Chaparro, MD
      • Contact: Kenia Capdevilla
    • Pensacola, Florida, United States, 32504
      • Recruiting
      • Ascension Sacred Heart
      • Principal Investigator: Rohit Amin
      • Contact: Walid Kara
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Recruiting
      • Piedmont
      • Contact: Gigi Davis, RN
      • Principal Investigator: Kent Nilsson
  • Illinois
    • Downers Grove, Illinois, United States, 60515
      • Active, not recruiting
      • Advocate Health System
    • Palos Park, Illinois, United States, 60464
      • Recruiting
      • Heart Care Centers of Illinois (HCCI)
      • Contact: Jessica Kwak
      • Principal Investigator: Chirag Rajyaguru
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Ascension St. Vincent's
      • Contact: Taylor Gilliam
      • Principal Investigator: Ashwin Ravichandran
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center (KUMC)
      • Principal Investigator: Hirak Shah, MD
      • Contact: Yolanda Murr
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Active, not recruiting
      • University of Maryland
    • Baltimore, Maryland, United States, 21239
      • Recruiting
      • Medstar
      • Contact: Rebecca Comaty
      • Principal Investigator: Erika Feller
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Recruiting
      • Tufts Medical Center
      • Contact: Gaurav Das
      • Principal Investigator: Michael Kiernan, MD
    • Boston, Massachusetts, United States, 02118
      • Not yet recruiting
      • Boston Medical Center Corporation
      • Principal Investigator: Nir Ayalon, MD
      • Contact: Nir Ayalon, MD
    • Boston, Massachusetts, United States, 02215
      • Active, not recruiting
      • Beth Israel Deaconess Medical Center (BIDMC)
  • Michigan
    • Howell, Michigan, United States, 48843
      • Recruiting
      • Ascension Providence Hospital Cardiology - Heart Cardiology
      • Contact: Yulia Abidov
      • Principal Investigator: Marcel Zughaib, MD
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • University of Minnesota
      • Contact: Julie Dicken
      • Principal Investigator: Tamas Alexy, MD
    • Minneapolis, Minnesota, United States, 55407
      • Active, not recruiting
      • Minneapolis Heart Institute Foundation
    • Saint Cloud, Minnesota, United States, 56303
      • Recruiting
      • Centra Care Heart Center
      • Contact: Nathan Warnert
      • Principal Investigator: Jamie Pelzel, MD
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Recruiting
      • St. Lukes/ Mid-American Heart Institute
      • Contact: Amanda Huffman
      • Principal Investigator: Michael Nassif, MD
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
      • Principal Investigator: Justin Vader, MD
      • Contact: Jean Flanagan
  • New York
    • New York, New York, United States, 10019
      • Recruiting
      • Mount Sinai West
      • Contact: Sajiny John
      • Principal Investigator: Johanna Contreras, MD
    • New York, New York, United States, 10029
      • Recruiting
      • Mount Sinai
      • Contact: Noah Moss
      • Principal Investigator: Noah Moss, MD
    • New York, New York, United States, 10075
      • Recruiting
      • Lenox Hill/ Northwell Health
      • Principal Investigator: Sirish Vullaganti, MD
      • Contact: Virgenmina (Angie) Lugaro
    • Stony Brook, New York, United States, 11794
      • Recruiting
      • Stony Brook University Med Center
      • Principal Investigator: Hal Skopicki, MD
      • Contact: Indre Caikauskaite
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
      • Principal Investigator: Marat Fudim, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati
      • Principal Investigator: Vlad Cotarlan, MD
      • Contact: Harshada More
    • Cincinnati, Ohio, United States, 45219
      • Active, not recruiting
      • The Christ Hospital- Cincinnati
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospital (Cleveland)
      • Contact: Monique Robinson, MD
      • Principal Investigator: Monique Robinson, MD
  • Oregon
    • Portland, Oregon, United States, 97239
      • Active, not recruiting
      • Oregon Health Science Portland
    • Portland, Oregon, United States, 97225
      • Recruiting
      • Providence St. Vincent's - Portland
      • Contact: Dr. Vidang Nguyen, MD; Email: vidang.nguyen@providence.org
      • Principal Investigator: Vidang Nguyen
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Active, not recruiting
      • Penn State Health
    • Pittsburgh, Pennsylvania, United States, 15213
      • Active, not recruiting
      • UPMC
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Active, not recruiting
      • PRISMA Health- Upstate
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Sanford
      • Contact: Diana Ibarra-Garcia
      • Principal Investigator: Marian Petrasko, MD
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt
      • Contact: Jaime Rich
      • Principal Investigator: Sandip Zalawadiya, MD
  • Texas
    • Austin, Texas, United States, 78756
      • Active, not recruiting
      • Austin Heart
    • Dallas, Texas, United States, 75240
      • Recruiting
      • Medical City Healthcare Dallas
      • Contact: Mona Hedra
      • Principal Investigator: Claudius Mahr, MD
    • Fort Worth, Texas, United States, 76110
      • Recruiting
      • Baylor Scott & White -Dallas
      • Principal Investigator: Cesar Guerrero, MD
      • Contact: Cesar Guerrero, MD
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • Baylor/Texas Heart
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Methodist San Antonio
      • Contact: Marina Martin
      • Principal Investigator: Chandra Kunavarapu
    • Temple, Texas, United States, 76508
      • Recruiting
      • Baylor - Temple
      • Contact: Amy Watts
      • Principal Investigator: Jaime Hernandez, MD
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Active, not recruiting
      • University of Vermont
  • Washington
    • Everett, Washington, United States, 98201
      • Recruiting
      • Providence Everett
      • Principal Investigator: Feng Wang, MD
      • Contact: Becca Watson
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Active, not recruiting
      • West Virginia University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin
      • Contact: Karen Olson
      • Principal Investigator: Peter Marogil, MD
    • Milwaukee, Wisconsin, United States, 53215
      • Active, not recruiting
      • Advocate Aurora St. Luke's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria 1. Subject has given written informed consent 2. Male or female, at least 18 years of age 3. Diagnosis and treatment of HF (regardless of LVEF) for ≥ 3 months and NYHA Class II HF (NYHA II Cohort) or NYHA III (NYHA III Cohort) at time of Screening

4. 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.

1. 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 Screening/Enrollment

2. 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 Screening/Enrollment 5. NYHA II Cohort- HF related hospitalization within 6 months (last hospitalization should be 30 days before Screening /Enrollment) 5. NYHA III Cohort -HF related hospitalization within 12 month (last hospitalization should be 30 days before Screening/Enrollment)

   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:

   1. 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))
   2. 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)
   3. 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)
   4. Subjects who have had a major cardiovascular (CV) event (e.g., myocardial infarction, stroke) within 3 months of the Screening Visit
   5. Unrepaired severe valvular disease
   6. 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)
   7. Subjects with known coagulation disorders
   8. 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
   9. Known history of life-threatening allergy to contrast dye.
   10. Subjects whereby RHC is contraindicated
   11. Subjects with an active infection at the Cordella Sensor Implant Visit
   12. Subjects with a GFR <20 ml/min or who are on chronic renal dialysis
   13. 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
   14. 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
   15. Subjects who are pregnant or breastfeeding
   16. 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
   17. Severe illness, other than heart disease, which would limit survival to <2 years
   18. Subjects whose clinical condition, in the opinion of the Investigator, makes them an unsuitable candidate for the study
   19. Subjects enrolled in another investigational trial with an active Treatment Arm
   20. Subject who is in custody by order of an authority or a court of law

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NYHA II Treatment Arm; 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; 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)
Experimental: NYHA II Active Control Arm; 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. Once the primary endpoint (24 months) is met, subjects and clinicians will be unblinded to PAP.	Device: Cordella™ Pulmonary Artery Sensor System; 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)
Experimental: NYHA II Crossover Arm; 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; 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)
Experimental: NYHA III Phase I Treatment Arm; 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; 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)
Experimental: NYHA III Phase I Active Control Arm; 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. Once the primary endpoint (6 months) is met, subjects and clinicians will be unblinded to PAP.	Device: Cordella™ Pulmonary Artery Sensor System; 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)
Experimental: NYHA III Clinician-Directed Patient Self-Management Arm (randomized); This is Phase II / Randomization #2 following implant provided patient meets eligiibity criteria. Subjects will be instructed to take their PAP measurements daily in addition to their weight, BP, SpO2, and HR. All data, including PAP, will be visible to the patient. Subjects will manage their diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines. Clinicians will oversee the patient self-management to target PAP per protocol specific Treatment Guidelines and according to Guideline-Directed Medical Therapy.	Device: Cordella™ Pulmonary Artery Sensor System; 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)
Experimental: NYHA III Clinician Management Arm (randomized); This is Phase II / Randomization #2 following implant provided patient meets eligiibity criteria. Subjects will be instructed to take their PAP measurements daily in addition to their weight, BP, SpO2, and HR. All data, including PAP, will be visible to the patient. Subjects will manage their diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines. Clinicians will manage the patients to target PAP per protocols specific to Treatment Guidelines and according to Guideline Directed Medical Therapy.	Device: Cordella™ Pulmonary Artery Sensor System; 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)
Experimental: NYHA III Clinician Management Arm (Not randomized); Subject will not be randomized if they do not meet eligibility criteria to potentially be randomized to Clinician-Directed Patient Self-Management. Subjects will be instructed to take their PAP measurements daily in addition to their weight, BP, SpO2, and HR. All data, including PAP, will be visible to the patient. Subjects will manage their diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines. Clinicians will manage the patients to target PAP per protocols specific to Treatment Guidelines and according to Guideline Directed Medical Therapy.	Device: Cordella™ Pulmonary Artery Sensor System; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Efficacy- NYHA II Cohort - 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- NYHA III Cohort (Phase I) - a composite of HF events or death from cardiovascular disease at 6 months	A composite of HF events or death from cardiovascular disease at 6 months	12 months
Efficacy- NYHA III Cohort (Phase II) - A test of non-inferiority at 12 months of the percentage of patients at or below trend seated mPAP of 25 mmHg in (i) Clinician-Directed Patient Self-Management vs. (ii) Clinician Management Arm	A test of non-inferiority at 12 months of the percentage of patients at or below trend seated mPAP of 25 mmHg in (i) Clinician-Directed Patient Self-Management vs. (ii) Clinician Management Arm	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations	-Incidence of HFH at 12, 18, and 24 months	12 months, 18 months and 24 months
Efficacy - NYHA II Cohort & NYHA III Cohort- 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 - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations	Combined outcome of : First and recurrent HF Hospitalizations; Urgent HF Visits; all-cause mortality	12 month
Efficacy - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations	Length of stay	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - All-cause mortality	All-cause mortality	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Death from cardiovascular disease	Death from cardiovascular disease	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Urgent HF visits	Urgent HF visits	Duration of study (to 5 years)
Efficacy - NYHA II Cohort - Incidence of HF hospitalizations or all-cause mortality	Incidence of HF hospitalizations or all-cause mortality	12 months
Efficacy - NYHA III Cohort - 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-NYHA II Cohort & NYHA III Cohort -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 (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - 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 (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Heart failure related medication changes	Heart failure related medication changes	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Change in PAP from baseline	Change in PAP from baseline	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Change in PAP from baseline as measured by echocardiogram (ECHO) and evaluated by anECHO 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 (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Patient Outcome Measures as measured by KCCQ, Brief Illness Perception Questionnaire, andEuroQol-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 (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Functional status improvement as measured by NYHA classification and 6MWT	Functional status improvement as measured by NYHA classification and 6MWT	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - HFH stratified by ejection fraction (HFrEF, HFmrEF, HFpEF, and HF recovered EF) and baselineenrollment ECHO estimated systolic PAP	HFH stratified by ejection fraction (HFrEF,	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Mortality by baseline EF (HFrEF, HFmrEF, HFpEF, HF recovered EF), and baseline enrollmentECHO estimated systolic PAP	Mortality by baseline EF (HFrEF, HFmrEF,	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Days alive outside hospital (DAOH)	Days alive outside hospital (DAOH)	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Health Economic Analysis	Health Economic Analysis	Duration of study (to 5 years)
Efficacy - NYHA II Cohort & NYHA III Cohort - Adherence to regular PAP and vital sign measurements including a sub-analysis on subjectswho 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 (to 5 years)
Safety - NYHA II Cohort - Freedom from device/system related complications at 12 months	Freedom from device/system related complications at 12 months	Duration of study (to 5 years)
Safety - NYHA III Cohort - Freedom from pressure sensor failure at 12 months	Freedom from pressure sensor failure at 12 months	Duration of study (to 5 years)
Safety - NYHA II Cohort & NYHA III Cohort - Pressure sensor failure rate throughout the study	Pressure sensor failure rate throughout the study	Duration of study (to 5 years)
Safety - NYHA II Cohort & NYHA III Cohort - Frequency of serious adverse events throughout the study	Frequency of serious adverse events throughout the study	Duration of study (to 5 years)
Safety - NYHA II Cohort & NYHA III Cohort - 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 (to 5 years)
Safety - NYHA III Cohort - Freedom from device/system related complications at 24 months	Freedom from device/system related complications at 24 months	Duration of study (to 5 years)
Safety - NYHA III Cohort - Freedom from pressure sensor failure at 24 months	Freedom from pressure sensor failure at 24 months	Duration of study (to 5 years)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety - NYHA III Cohort Phase II only: Incidence of serious adverse events at 12 months post Phase II randomization	Incidence of serious adverse events at 12 months post Phase II randomization	12 months

Collaborators and Investigators

• Sponsor: Endotronix, Inc.
• Investigators: Study Director: Andrea Sauerland, Endotronix, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2023
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2033

Study Registration Dates

• First Submitted: June 26, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Cardiovascular Disease; Heart Disease; Pulmonary Artery Pressure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Cardiovascular Diseases; Heart Diseases
• Other Study ID Numbers: ETX-HFS-PA-04

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: Yes
• product manufactured in and exported from the U.S.: No