PROACTIVE-HF IDE Trial Heart Failure NYHA Class III

NCT04089059 | Active Not Recruiting Results DMC FDA Device

• 1 other identifier: ETX-HFS-PA-03
• Study Type: interventional
• Target: 738
• Locations: 3 countries
• Sites: 74

Brief Summary

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).

Conditions

Heart Failure NYHA Class III

Keywords

Heart Failure; Heart Disease; Cardiovascular Disease; Pulmonary Artery Pressure

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (18)

• HF Hospitalizations

  6 Months prior to implant and 6 months post implant

• HF Hospitalizations or Emergency Department/Hospital Outpatient IV Diuretic Visits.

  6 months

• Mortality

  6 Months

• IV Diuretic Visits

  6 Months

• Pulmonary Artery Pressure (PAP)

  6 months

Study Arms (1)

Treatment Arm

OTHER

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

Interventions

Cordella™ Pulmonary Artery Sensor System DEVICE

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. 1. Cordella Sensor 2. Cordella Delivery System 3. myCordella Patient Reader 4. Reader Dock 5. Cordella Calibration Equipment (CalEQ) 6. myCordella Hub 7. Cordella Data Analysis Platform (CDAP)

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Endotronix, Inc.: lead

Study Sites (74)

Ascension St Vincent's

Birmingham, Alabama, 35235, United States

Location

Huntsville Hospital

Huntsville, Alabama, 35801, United States

Location

Phoenix Cardiovascular Research Group/Insight

Phoenix, Arizona, 85018, United States

Location

Loma Linda University

Loma Linda, California, 92354, United States

Location

Eisenhower Medical Center

Rancho Mirage, California, 92270, United States

Location

UCSD

San Diego, California, 92037, United States

Location

Kaiser San Francisco

San Francisco, California, 94118, United States

Location

UCSF Medical Center

San Francisco, California, 94143, United States

Location

Kaiser Santa Clara

Santa Clara, California, 95051, United States

Location

South Denver Cardiology

Littleton, Colorado, 80120, United States

Location

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

Baptist Health South Florida

Miami, Florida, 33176, United States

Location

Ascension Sacred Heart

Pensacola, Florida, 32504, United States

Location

USF Health

Tampa, Florida, 33609, United States

Location

Cleveland Clinic

Weston, Florida, 33331, United States

Location

Piedmont Athens

Athens, Georgia, 30600, United States

Location

Queens Medical Center

Honolulu, Hawaii, 96813, United States

Location

Northwestern

Chicago, Illinois, 60611, United States

Location

U of Chicago

Chicago, Illinois, 60637, United States

Location

Heart Centers of Illinois

Palos Park, Illinois, 60464, United States

Location

OSF Healthcare

Peoria, Illinois, 61107, United States

Location

Ascension St Vincent's

Indianapolis, Indiana, 46260, United States

Location

University of Iowa Medical Center

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, 66160, United States

Location

University Of Louisville

Louisville, Kentucky, 40202, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Medstar

Baltimore, Maryland, 21239, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital (Mass General Brigham)

Boston, Massachusetts, 02215, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Centra Care Heart Center

Saint Cloud, Minnesota, 56303, United States

Location

St. Lukes/ Mid-American Heart Institute

Kansas City, Missouri, 64111, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

The Valley Hospital

Ridgewood, New Jersey, 07450, United States

Location

Mount Sinai

New York, New York, 10029, United States

Location

NYU Langone Health

New York, New York, 11794, United States

Location

New York Presbyterian Queens

Queens, New York, 11355, United States

Location

Stony Brook University Med Center

Stony Brook, New York, 11794, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health Science Portland

Portland, Oregon, 97239, United States

Location

Thomas Jefferson Abington

Abington, Pennsylvania, 19001, United States

Location

Penn State Health

Hershey, Pennsylvania, 17033, United States

Location

Penn Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

PRISMA Midlands - Palmetto

Columbia, South Carolina, 29203, United States

Location

PRISMA Health- Upstate

Greenville, South Carolina, 29605, United States

Location

Sanford

Sioux Falls, South Dakota, 57105, United States

Location

Tennova Healthcare (Turkey Creek Medical Center)

Knoxville, Tennessee, 37934, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Austin Heart

Austin, Texas, 78756, United States

Location

Craig Cardiovascular Center

Gonzales, Texas, 78155, United States

Location

Baylor/Texas Heart

Houston, Texas, 77030, United States

Location

Houston Methodist

Houston, Texas, 77030, United States

Location

University of Texas/Hermann Memorial

Houston, Texas, 77030, United States

Location

Baylor - Round Rock

Round Rock, Texas, 78655, United States

Location

Methodist Healthcare System

San Antonio, Texas, 78229, United States

Location

Baylor - Temple

Temple, Texas, 76508, United States

Location

University of Vermont

Burlington, Vermont, 05401, United States

Location

Sentara Healthcare

Norfolk, Virginia, 22191, United States

Location

Valley Health System/Winchester Medical Center

Winchester, Virginia, 22601, United States

Location

University of Washington

Seattle, Washington, 98196, United States

Location

Providence Health Care

Spokane, Washington, 99204, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Cardiovascular Center OLV Aalst

Aalst, Belgium

Location

ZNA Middlheim

Antwerp, Belgium

Location

Ziekenhuis- Oost Limburg

Genk, Belgium

Location

University Hospital Galway

Galway, Ireland

Location

Related Publications (2)

• Pourafshar N, Daneshmand A, Karimi A, Wilcox CS. Methods for the Assessment of Volume Overload and Congestion in Heart Failure. Kidney360. 2024 Oct 1;5(10):1584-1593. doi: 10.34067/KID.0000000000000553. Epub 2024 Aug 20.

  PMID: 39480670 DERIVED

• Guichard JL, Bonno EL, Nassif ME, Khumri TM, Miranda D, Jonsson O, Shah H, Alexy T, Macaluso GP, Sur J, Hickey G, McCann P, Cowger JA, Badiye A, Old WD, Raza Y, Masha L, Kunavarapu CR, Bennett M, Sharif F, Kiernan M, Mullens W, Chaparro SV, Mahr C, Amin RR, Stevenson LW, Hiivala NJ, Owens MM, Sauerland A, Forouzan O, Klein L. Seated Pulmonary Artery Pressure Monitoring in Patients With Heart Failure: Results of the PROACTIVE-HF Trial. JACC Heart Fail. 2024 Nov;12(11):1879-1893. doi: 10.1016/j.jchf.2024.05.017. Epub 2024 Aug 14.

  PMID: 39152983 DERIVED

MeSH Terms

Conditions

Heart Failure; Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

* The major limitation of PROACTIVE-HF is its open-label, single arm design and the absence of a concurrent control arm, though endpoint assessment was blinded and performed by an independent adjudication committee * There are known limitations of interpretation of KCCQ in unblinded studies. * As prior studies utilized supine PAP for remote management of HF, clinician lack of familiarity with orthostatic PAP physiology may have influenced decision making.

Results Point of Contact

• Title: Liviu Klein
• Organization: UCSF School of Medicine

liviu.klein@ucsf.edu

415-476-2143

Study Officials

• Andrea Sauerland

  Endotronix, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2019
• First Posted: September 13, 2019
• Study Start: January 10, 2020
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 3, 2025
• Results First Posted: March 3, 2025

Record last verified: 2024-12

Locations

BE (3); US (70); IE (1)