Clinical trial NCT05934487: PROACTIVE-HF-2 Trial Heart Failure NYHA Class II and III
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure NYHA Class II
Heart Failure NYHA Class III
Heart Failure
Keywords: Heart Failure
Heart Disease
Cardiovascular Disease
Pulmonary Artery Pressure
Lead sponsor: Endotronix, Inc.
Sponsor class: INDUSTRY
First posted: 2023-07-07
Enrollment: 1750
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief 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:

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.


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 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

Primary outcomes:
measure: Efficacy- NYHA II Cohort - A composite of first HF event or death from Cardiovascular Death up to 24 months.
timeFrame: 24 months
measure: Efficacy- NYHA III Cohort (Phase I) - a composite of HF events or death from cardiovascular disease at 6 months
timeFrame: 12 months
measure: Safety- Randomized Arm- Freedom from device/system related complication
timeFrame: 24 months
measure: Safety- Randomized Arm-Freedom from pressure sensor failure
timeFrame: 24 months
measure: Safety- Single Arm-Freedom from device/system related complication
timeFrame: 12 months
measure: Safety- Single Arm- Freedom from pressure sensor failure
timeFrame: 12 months
measure: 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
timeFrame: 12 months
Secondary outcomes:
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations
timeFrame: 12 months, 18 months and 24 months
measure: Efficacy - NYHA II Cohort & NYHA III Cohort- HF Hospitalizations
timeFrame: 12 months and 24 months
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations
timeFrame: 12 month
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - All-cause mortality
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Death from cardiovascular disease
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Urgent HF visits
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort - Incidence of HF hospitalizations or all-cause mortality
timeFrame: 12 months
measure: Efficacy - NYHA III Cohort - Composite of first HF event (HF hospitalization or urgent HF visit or death from cardiovascular disease (CVD)
timeFrame: Up to 24 months
measure: 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
timeFrame: Duration of study (to 5 years)
measure: 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.
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Heart failure related medication changes
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Change in PAP from baseline
timeFrame: Duration of study (to 5 years)
measure: 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
timeFrame: Duration of study (to 5 years)
measure: 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)
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Functional status improvement as measured by NYHA classification and 6MWT
timeFrame: Duration of study (to 5 years)
measure: 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
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Mortality by baseline EF (HFrEF, HFmrEF, HFpEF, HF recovered EF), and baseline enrollmentECHO estimated systolic PAP
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Days alive outside hospital (DAOH)
timeFrame: Duration of study (to 5 years)
measure: Efficacy - NYHA II Cohort & NYHA III Cohort - Health Economic Analysis
timeFrame: Duration of study (to 5 years)
measure: 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
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA II Cohort - Freedom from device/system related complications at 12 months
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA III Cohort - Freedom from pressure sensor failure at 12 months
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA II Cohort & NYHA III Cohort - Pressure sensor failure rate throughout the study
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA II Cohort & NYHA III Cohort - Frequency of serious adverse events throughout the study
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA II Cohort & NYHA III Cohort - Frequency of implant procedure and procedure related adverse events and serious adverse events
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA III Cohort - Freedom from device/system related complications at 24 months
timeFrame: Duration of study (to 5 years)
measure: Safety - NYHA III Cohort - Freedom from pressure sensor failure at 24 months
timeFrame: Duration of study (to 5 years)
Other outcomes:
measure: Safety - NYHA III Cohort Phase II only: Incidence of serious adverse events at 12 months post Phase II randomization
timeFrame: 12 months
Locations:
city: Phoenix
country: United States
facility: St. Joseph's Hospital and Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: USC
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: Miami
country: United States
facility: Baptist Health South Florida
state: Florida
city: Pensacola
country: United States
facility: Ascension Sacred Heart
state: Florida
city: Atlanta
country: United States
facility: Piedmont
state: Georgia
city: Downers Grove
country: United States
facility: Advocate Health System
state: Illinois
city: Palos Park
country: United States
facility: Heart Care Centers of Illinois (HCCI)
state: Illinois
city: Indianapolis
country: United States
facility: Ascension St. Vincent's
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center (KUMC)
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Baltimore
country: United States
facility: MedStar
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (BIDMC)
state: Massachusetts
city: Howell
country: United States
facility: Ascension Providence Hospital Cardiology - Heart Cardiology
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: St. Cloud
country: United States
facility: Centra Care Heart Center
state: Minnesota
city: Kansas City
country: United States
facility: St. Lukes/ Mid-American Heart Institute
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Mount Sinai West
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Lenox Hill/ Northwell Health
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Med Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital- Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: University Hospital (Cleveland)
state: Ohio
city: Portland
country: United States
facility: Providence St. Vincent's - Portland
state: Oregon
city: Portland
country: United States
facility: Oregon Health Science Portland
state: Oregon
city: Hershey
country: United States
facility: Penn State Health
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Greenville
country: United States
facility: PRISMA Health- Upstate
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Medical City Healthcare Dallas
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott & White -Dallas
state: Texas
city: Houston
country: United States
facility: Baylor/Texas Heart
state: Texas
city: San Antonio
country: United States
facility: Methodist San Antonio
state: Texas
city: Temple
country: United States
facility: Baylor - Temple
state: Texas
city: Burlington
country: United States
facility: University of Vermont
state: Vermont
city: Everett
country: United States
facility: Providence Everett
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Advocate Aurora St. Luke's
state: Wisconsin
Study officials:
affiliation: Endotronix, Inc.
name: Andrea Sauerland
role: STUDY_DIRECTOR
References: