PROACTIVE-HF IDE Trial Heart Failure NYHA Class III (PROACTIVE-HF)

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)

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure NYHA Class III
• Intervention / Treatment: Device: Cordella™ Pulmonary Artery Sensor System

• Study Type: Interventional
• Enrollment (Actual): 738
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
    • Cardiovascular Center OLV Aalst
  • Antwerp, Belgium
    • ZNA Middlheim
  • Genk, Belgium
    • Ziekenhuis- Oost Limburg
• Ireland
  • Galway, Ireland
    • University Hospital Galway
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • Ascension St Vincent's
    • Huntsville, Alabama, United States, 35801
      • Huntsville Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Phoenix Cardiovascular Research Group/Insight
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University
    • Rancho Mirage, California, United States, 92270
      • Eisenhower Medical Center
    • San Diego, California, United States, 92037
      • UCSD
    • San Francisco, California, United States, 94143
      • UCSF Medical Center
    • San Francisco, California, United States, 94118
      • Kaiser San Francisco
    • Santa Clara, California, United States, 95051
      • Kaiser Santa Clara
  • Colorado
    • Littleton, Colorado, United States, 80120
      • South Denver Cardiology
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
  • Florida
    • Miami, Florida, United States, 33176
      • Baptist Health South Florida
    • Pensacola, Florida, United States, 32504
      • Ascension Sacred Heart
    • Tampa, Florida, United States, 33609
      • USF Health
    • Weston, Florida, United States, 33331
      • Cleveland Clinic
  • Georgia
    • Athens, Georgia, United States, 30600
      • Piedmont Athens
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queens Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern
    • Chicago, Illinois, United States, 60637
      • U of Chicago
    • Palos Park, Illinois, United States, 60464
      • Heart Centers of Illinois
    • Peoria, Illinois, United States, 61107
      • OSF Healthcare
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Ascension St Vincent's
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Medical Center
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center (KUMC)
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
    • Baltimore, Maryland, United States, 21239
      • MedStar
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (BIDMC)
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital (Mass General Brigham)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Saint Cloud, Minnesota, United States, 56303
      • Centra Care Heart Center
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Lukes/ Mid-American Heart Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai
    • New York, New York, United States, 11794
      • NYU Langone Health
    • Queens, New York, United States, 11355
      • New York Presbyterian Queens
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Med Center
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43210
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Science Portland
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Thomas Jefferson Abington
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Medicine
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • PRISMA Midlands - Palmetto
    • Greenville, South Carolina, United States, 29605
      • PRISMA Health- Upstate
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Sanford
  • Tennessee
    • Knoxville, Tennessee, United States, 37934
      • Tennova Healthcare (Turkey Creek Medical Center)
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt
  • Texas
    • Austin, Texas, United States, 78756
      • Austin Heart
    • Gonzales, Texas, United States, 78155
      • Craig Cardiovascular Center
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Houston, Texas, United States, 77030
      • Baylor/Texas Heart
    • Houston, Texas, United States, 77030
      • University of Texas/Hermann Memorial
    • Round Rock, Texas, United States, 78655
      • Baylor - Round Rock
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System
    • Temple, Texas, United States, 76508
      • Baylor - Temple
  • Vermont
    • Burlington, Vermont, United States, 05401
      • University of Vermont
  • Virginia
    • Norfolk, Virginia, United States, 22191
      • Sentara Healthcare
    • Winchester, Virginia, United States, 22601
      • Valley Health System/Winchester Medical Center
  • Washington
    • Seattle, Washington, United States, 98196
      • University of Washington
    • Spokane, Washington, United States, 99204
      • Providence Health Care
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (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 left ventricular ejection fraction (LVEF)) for ≥ 3 months and NYHA Class III HF at time of Screening
4. 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.

5. 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:

   1. Subjects with LVEF ≤ 50%: NT-proBNP ≥ 1500 pg/mL.
   2. 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
6. Subjects should be on diuretic therapy
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. Intolerance to all neuro-hormonal antagonists (i.e., intolerance to ACE-I, ARB, ARNI, and beta-blockers) due to hypotension or renal dysfunction
2. ACC/AHA Stage D refractory HF (including having received or currently receiving pharmacologic circulatory support with inotropes)
3. 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)
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 Sensor Implant Visit
12. Subjects with a Glomerular Filtration Rate (GFR) <25 ml/min or who are on chronic renal dialysis
13. Implanted with Cardiac Resynchronization Therapy (CRT)-Pacemaker (CRT-P) or CRT-Defibrillator (CRT-D) for less than 90 days prior to screening visit
14. Received or are likely to receive an advanced therapy (e.g. mechanical circulatory support or lung or heart transplant) in the next 12 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 <1 year
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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Treatment Arm; 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; 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy 6 Month Incidence of HF Related Hospitalizations (HFH) or All-cause Mortality	The primary efficacy endpoint was the 6-month incidence of HF related hospitalizations or all-cause mortality in the modified Intent-to-Treat (mITT) population. As per the approved protocol/CIP, for study success the upper confidence bound of the observed event rate in the mITT population was required to be less than the performance goal (PG) of 0.43 events per patient 6-month, or equivalently, the corresponding p-value from the hypothesis test of 6-month incidence rate compared to PG was less than 0.025. Furthermore, the observed incidence rate was required to be less than 0.37. The 6-month incidence rate was derived using a Poisson regression with the number of events as the dependent variable and the exposure time as an offset term. In these analyses, a subject's exposure time was defined as the time to death, early study discontinuation, or 6 months (whichever occurred first).	6 months
Safety: Freedom From Device/System Related Complication	A device/system related complication (DSRC) is defined as an AE that is, or is possibly, related to the device/system (Cordella PA Sensor or electronic components) and is either treated invasively (other than intramuscular medication or diagnostic RHC) or results in subject´s death or explant of the device. The first primary safety endpoint describes freedom from a DSRC through 6 months and was tested against the null rate of 90%.	6 months
Safety: Freedom From Pressure Sensor Failure	A pressure sensor failure (PSF) occurs when the sensor malfunctions to the point that no readings can be obtained from the sensor after all attempts are exhausted including troubleshooting the system to rule out any problems with the electronic components. The second primary safety endpoint describes freedom from Pressure Sensor Failure through 6 months, it was tested against the null rate of 95%.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HF Hospitalizations	Number of HF Hospitalizations at 6 months post-implant compared to the number of HF Hospitalizations in the 6 months prior to implant	6 Months prior to implant and 6 months post implant
HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits.	Incidence rate of HF Hospitalizations, Emergency Department/ Hospital Outpatient IV diuretic visits of Former Control Arm and Modified Intent to Treat at 6 months post implant, added together with equal weighting into a total number of events.	6 months
Mortality	Cardiac and all-cause mortality	6 Months
IV Diuretic Visits	Intravenous (IV) diuretic visits	6 Months
Pulmonary Artery Pressure (PAP)	Change in PAP: a. From Baseline through 6 months in subjects with a baseline mPAP i. above target range ii. within or below target range iii. Overall	6 months
Device Success	Proportion of device success as documented by ability of the System to successfully transmit PAP data transmit PAP data	6 Months
Kansas City Cardiomyopathy Questionnaire (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. From 23-items, the Overall Summary Score (OSS) will be calculated. In the OSS, each of the 23 items are converted onto a 0 to 100 scale using this formula: (Raw score - Minimum Raw Score)/(Maximum Raw Score - Minimum Raw Score) * 100. Then these are averaged across the 23 items. A score of 100 (the maximum score) would indicate maximum quality of life relating to heart failure and a score of 0 (scale minimum) would indicate the worst possible quality of life relating to heart failure, with higher scores generally indicating higher quality of life.	6 Months
NYHA	New York Heart Association (NYHA) Classification at 6 months. The New York Heart Association (NYHA) Classification provides a way of classifying the extent of heart failure by classifying patients in one of four categories based on their limitations during physical activity and in degree of shortness of breath and or angina pain. Class I is the least severe and Class IV is the most severe. The classes are: 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. Comfortable only at rest. Class IV - Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients.	6 Months
6-Minute Walk Test	Functional status improvement, as measured by 6-Minute Walk Test total distance walked. The 6-Minute Walk Test (6MWT) is a test that measures the total distance an individual can walk on a flat, hard surface in 6 minutes. It is commonly used to evaluate functional exercise capacity in patients with conditions including heart failure. The minimum score possible is 0, which would represent an inability to walk any distance. There is no maximum score, as a patient could theoretically walk any distance in 6 minutes though 800 meters considered the top reference range, which is what would be expected by elite athletes. Higher score indicate greater higher exercise capacity and lower scores indicate lower exercise capacity.	6 Months
Number and Percent of Patients With Serious Adverse Events	Number and percent of patients with serious adverse events throughout the study (site-reported).	6 Months
Incidence of HF Hospitalizations or All-cause Mortality	Incidence of HF Hospitalizations or all-cause mortality at 12 months calculated from Poisson regression.	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 months. NT-proBNP is a biomarker used to assess heart failure (HF). NT-proBNP levels vary widely and are reported in picograms per milliliter (pg/mL) or nanograms per liter (ng/L), with no predefined maximum value. Zero is a hypothetical minimum value though this is, in practice, not possible. In the current context, higher scores indicate more severe heart failure and lower levels indicate less severe heart failure.	6 months
Days Alive and Out of Hospital (DAOH)	Days Alive and Out of Hospital (DAOH) during the 6 months after implant	6 Months
Number of Heart Failure Related Medication Changes	Number of patients (%) with heart failure related medication changes in the 6 months after implant	6 Months
Number of HF Hospitalization or All-cause Mortality	Number of HF Hospitalizations or all-cause mortality at 12 months	12 months
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits, All-cause Mortality	Number of 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
Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV Diuretic Visits	Number of HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits at 6 months.	6 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	6 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2020
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: August 30, 2019
• First Submitted That Met QC Criteria: September 11, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: December 1, 2024

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
• Other Study ID Numbers: ETX-HFS-PA-03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes