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

Heart Failure NYHA Class III Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05934487
• Other study ID #: ETX-HFS-PA-04
• Status: Recruiting
• Phase: N/A
• Start date: November 29, 2023
• Est. completion date: September 2029

Study information

• Verified date: March 2024
• Source: Endotronix, Inc.
• Contact: Jami Smith
• Phone: +1-316-300-0882
• Email: jami.smith[@]endotronix.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1650
• Est. completion date: September 2029
• Est. primary completion date: September 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (Randomized Arm) or NYHA III (Single Arm) 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 randomization

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 randomization

5. 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:

1. Subjects with LVEF = 50%: NT-proBNP = 1000 pg/mL.

2. 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:

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure NYHA Class II
• 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, 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)

Locations

Country	Name	City	State
United States	TJ Abington	Abington	Pennsylvania
United States	Piedmont	Atlanta	Georgia
United States	Austin Heart	Austin	Texas
United States	MedStar	Baltimore	Maryland
United States	University of Maryland	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center (BIDMC)	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of Vermont	Burlington	Vermont
United States	Northwestern	Chicago	Illinois
United States	U of Chicago	Chicago	Illinois
United States	The Christ Hospital- Cincinnati	Cincinnati	Ohio
United States	University of Cincinnati	Cincinnati	Ohio
United States	PRISMA Midlands - Palmetto	Columbia	South Carolina
United States	Medical City Healthcare Dallas	Dallas	Texas
United States	South Denver Cardiology	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Advocate Health System	Downers Grove	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	St. Elizabeth's Healthcare	Edgewood	Kentucky
United States	Providence Everett	Everett	Washington
United States	Baylor Scott & White -Dallas	Fort Worth	Texas
United States	PRISMA Health- Upstate	Greenville	South Carolina
United States	Penn State Health	Hershey	Pennsylvania
United States	Baylor/Texas Heart	Houston	Texas
United States	Ascension Providence Hospital Cardiology - Heart Cardiology	Howell	Michigan
United States	Ascension St. Vincent's	Indianapolis	Indiana
United States	University of Iowa Medical Center	Iowa City	Iowa
United States	St. Lukes/ Mid-American Heart Institute	Kansas City	Missouri
United States	University of Kansas Medical Center (KUMC)	Kansas City	Kansas
United States	Loma Linda University	Loma Linda	California
United States	USC	Los Angeles	California
United States	University Of Louisville	Louisville	Kentucky
United States	University of Wisconsin	Madison	Wisconsin
United States	Baptist Health South Florida	Miami	Florida
United States	Advocate Aurora St. Luke's	Milwaukee	Wisconsin
United States	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt	Nashville	Tennessee
United States	Lenox Hill/ Northwell Health	New York	New York
United States	Mount Sinai	New York	New York
United States	Mount Sinai West	New York	New York
United States	NYU Langone Health	New York	New York
United States	Sentara Healthcare	Norfolk	Virginia
United States	University of Nebraska	Omaha	Nebraska
United States	Heart Care Centers of Illinois (HCCI)	Palos Park	Illinois
United States	Ascension Sacred Heart	Pensacola	Florida
United States	OSF Healthcare	Peoria	Illinois
United States	Penn Medicine (UPENN)	Philadelphia	Pennsylvania
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health Science Portland	Portland	Oregon
United States	Providence St. Vincent's - Portland	Portland	Oregon
United States	Centra Care Heart Center	Saint Cloud	Minnesota
United States	Washington University	Saint Louis	Missouri
United States	Methodist San Antonio	San Antonio	Texas
United States	San Diego Cardiac Care	San Diego	California
United States	UCSF Medical Center	San Francisco	California
United States	Sanford	Sioux Falls	South Dakota
United States	Providence Health Care	Spokane	Washington
United States	Stony Brook University Med Center	Stony Brook	New York
United States	Baylor - Temple	Temple	Texas
United States	Cleveland Clinic	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Endotronix, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Safety- Randomized Arm- Freedom from device/system related complication	Freedom from device/system related complication at 24 months	24 months
Primary	Safety- Randomized Arm-Freedom from pressure sensor failure	Freedom from pressure sensor failure at 24 months	24 months
Primary	Safety- Single Arm-Freedom from device/system related complication	Freedom from device/system related complication at 12 months	12 months
Primary	Safety- Single Arm- Freedom from pressure sensor failure	Freedom from pressure sensor failure at 12 months	12 months
Secondary	Efficacy - Randomized and Single Arm- HF Hospitalizations	-Incidence of HFH at 12, 18, and 24 months	12 months, 18 months and 24 months
Secondary	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
Secondary	Efficacy -Randomized and Single Arm - HF Hospitalizations	Combined outcome of : First and recurrent HF Hospitalizations; Urgent HF Visits; all-cause mortality	12 month
Secondary	Efficacy -Randomized and Single Arm - HF Hospitalizations	Length of stay	Duration of study
Secondary	Efficacy -Randomized and Single Arm - All-cause mortality	All-cause mortality	Duration of study
Secondary	Efficacy -Randomized and Single Arm - Death from cardiovascular disease	Death from cardiovascular disease	Duration of study
Secondary	Efficacy -Randomized and Single Arm - Urgent HF visits	Urgent HF visits	Duration of study
Secondary	Efficacy - Randomized Arm - Incidence of HF hospitalizations or all-cause mortality	Incidence of HF hospitalizations or all-cause mortality	12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Efficacy - Randomized and Single Arm - Heart failure related medication changes	Heart failure related medication changes	Duration of study
Secondary	Efficacy - Randomized and Single Arm - Change in PAP from baseline	Change in PAP from baseline	Duration of study
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Efficacy - Randomized and Single Arm - Days alive outside hospital (DAOH)	Days alive outside hospital (DAOH)	Duration of study
Secondary	Efficacy - Randomized and Single Arm - Health Economic Analysis	Health Economic Analysis	Duration of study
Secondary	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
Secondary	Safety - Randomized Arm - Freedom from device/system related complications at 12 months	Freedom from device/system related complications at 12 months	Duration of study
Secondary	Safety - Randomized Arm - Freedom from pressure sensor failure at 12 months	Freedom from pressure sensor failure at 12 months	Duration of study
Secondary	Safety - Randomized and Single Arm - Pressure sensor failure rate throughout the study	Pressure sensor failure rate throughout the study	Duration of study
Secondary	Safety - Randomized and Single Arm - Frequency of serious adverse events throughout the study	Frequency of serious adverse events throughout the study	Duration of study
Secondary	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
Secondary	Safety - Single Arm - Freedom from device/system related complications at 24 months	Freedom from device/system related complications at 24 months	Duration of study
Secondary	Safety - Single Arm - Freedom from pressure sensor failure at 24 months	Freedom from pressure sensor failure at 24 months	Duration of study