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

• ClinicalTrials.gov Identifier: NCT04089059
• Recruitment Status: Active, not recruiting
• First Posted: September 13, 2019
• Last Update Posted: April 7, 2023
• Sponsor: Endotronix, Inc.
• Information provided by (Responsible Party): Endotronix, Inc.

Tracking Information

• First Submitted Date: August 30, 2019
• First Posted Date: September 13, 2019
• Last Update Posted Date: April 7, 2023
• Actual Study Start Date: January 10, 2020
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 11, 2022)

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

Original Primary Outcome Measures (submitted: September 11, 2019)

• Mortality and HF Hospitalizations or Emergency Department/ Hospital Outpatient IV diuretic visits. [ Time Frame: 12 months ]
  Rate of mortality and HF Hospitalizations or Emergency Department/ Hospital Outpatient IV diuretic visits. The rate in each arm is calculated as the total number of observed events in each arm divided by the total observed exposure time in each arm from randomization through 12 months.
• Safety: Device/system related complication [ Time Frame: 12 months ]
  Freedom from device/system related complication at 12 months
• Safety: Pressure sensor failure [ Time Frame: 12 months ]
  Freedom from pressure sensor failure at 12 months

Current Secondary Outcome Measures (submitted: November 11, 2022)

• HF Hospitalizations [ Time Frame: 6 months and 12 months ]
  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
• HF Hospitalizations or Emergency Department/Hospital Outpatient IV diuretic visits. [ Time Frame: 6 and 12 months ]
  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
• Mortality [ Time Frame: 3 years ]
  Cardiac and all-cause mortality
• IV diuretic visits [ Time Frame: 3 years ]
  Intravenous (IV) diuretic visits
• Pulmonary Artery Pressure (PAP) [ Time Frame: 6 and 12 months ]
  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
• Device success [ Time Frame: 3 years ]
  Percentage of device success as documented by ability of the System to successfully transmit PAP data transmit PAP data
• KCCQ [ Time Frame: 3 years ]
  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.
• NYHA [ Time Frame: 3 years ]
  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
• NYHA and 6-Minute Walk Test [ Time Frame: 3 years ]
  Functional status improvement, as measured by NYHA and 6-Minute Walk Test
• Serious adverse events [ Time Frame: 3 years ]
  Frequency of serious adverse events throughout the study
• Incidence of HF Hospitalizations or all-cause mortality [ Time Frame: 12 months ]
  Incidence of HF Hospitalizations or all-cause mortality at 12 months
• N-terminal pro B-type Natriuretic Peptide (NT-proBNP [ Time Frame: 6 and 12 months ]
  Change of N-terminal pro B-type Natriuretic Peptide (NT-proBNP) from Baseline through 6 and 12 months
• Days Alive and Out of Hospital (DAOH) [ Time Frame: 3 years ]
  Days Alive and Out of Hospital (DAOH)
• Heart failure related Medication changes [ Time Frame: 3 years ]
  Heart failure related Medication changes
• HF Hospitalization or all-cause mortality [ Time Frame: 12 months ]
  Incidence of HF Hospitalizations or all-cause mortality at 12 months
• HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits, all-cause mortality [ Time Frame: 6 months ]
  Combined outcome of:

  1. First and recurrent Heart Failure Hospitalizations
  2. Emergency Department / Hospital Outpatient IV diuretic visits all-cause mortality at 6 months, added together with equal weighting into a total number of events.
• HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits [ Time Frame: 6 and 12 months ]
  HF Hospitalization, Emergency Department/Hospital Outpatient IV diuretic visits at 6 and 12 months
• Implant procedure and procedure related adverse events and serious adverse events [ Time Frame: 3 years ]
  Frequency of implant procedure and procedure related adverse events and serious adverse events

Original Secondary Outcome Measures (submitted: September 11, 2019)

• HF Hospitalizations [ Time Frame: 6 months and 12 months ]
  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
• HF Hospitalizations, Emergency Department/ Hospital Outpatient IV diuretic visits and all-cause mortality [ Time Frame: 6 months ]
  Combined outcome of

  1. First and recurrent HF Hospitalizations
  2. Emergency Department/ Hospital Outpatient IV diuretic visits
  3. all-cause mortality

  at 6 months, added together with equal weighting into a total number of events.
• Heart failure hospitalization or Emergency Department / Hospital Outpatient IV diuretic visits [ Time Frame: 6 months and 12 months ]
  Heart failure hospitalization or Emergency Department / Hospital Outpatient IV diuretic visits at 6 and 12 months
• Mortality [ Time Frame: 3 years ]
  Cardiac and all-cause mortality
• IV diuretic visits [ Time Frame: 3 years ]
  Intravenous (IV) diuretic visits
• Medication changes [ Time Frame: 3 years ]
  Heart failure related Medication changes will be collected and summarized by visit presenting the percentage of subjects with and without any change in Heart Failure related medication
• PAP I [ Time Frame: 3 years ]
  Change in PAP from Baseline
• PAP II [ Time Frame: 3 years ]
  Change in PAP before and after 6-Minute Walk Test
• PAP III [ Time Frame: 3 years ]
  Change in PAP for patients blinded (12 month) vs patients unblinded (12 month) to PAP measurements
• Device success [ Time Frame: 3 years ]
  Percentage of device success as documented by ability of the System to successfully transmit PAP data to a secure database
• KCCQ [ Time Frame: 3 years ]
  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.
• NYHA [ Time Frame: 3 years ]
  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
• NYHA and 6-Minute Walk Test [ Time Frame: 3 years ]
  The NYHA functional classification categorizes the extent of heart failure by placing subjects in one of four (I, II, III, IV) categories based on how much they are limited during physical activity and symptoms of shortness of breath and/or angina. Shifts in NYHA functional classification from baseline over all post-baseline visits will be presented . 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
• Pressure sensor failure [ Time Frame: 3 years ]
  Pressure sensor failure rate throughout the study
• Serious adverse events [ Time Frame: 3 years ]
  Frequency of serious adverse events throughout the study

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PROACTIVE-HF IDE Trial Heart Failure NYHA Class III
• Official Title: 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)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Heart Failure NYHA Class III

Intervention

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.

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)

Study Arms

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).

Intervention: Device: Cordella™ Pulmonary Artery Sensor System

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 5, 2023): 456
• Original Estimated Enrollment (submitted: September 11, 2019): 970
• Estimated Study Completion Date: March 2026
• Estimated Primary Completion Date: September 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Ireland, United States

Administrative Information

• NCT Number: NCT04089059
• Other Study ID Numbers: ETX-HFS-PA-03
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Device Product Not Approved or Cleared by U.S. FDA: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Endotronix, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Endotronix, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Andrea Sauerland; Endotronix, Inc.

• PRS Account: Endotronix, Inc.
• Verification Date: April 2023