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

Endotronix

Status: Enrolling

Conditions: Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure

Treatments: Device: Cordella™ Pulmonary Artery Sensor System

Study type: Interventional

Funder types: Industry

Identifiers

NCT05934487

ETX-HFS-PA-04

Details and patient eligibility

About

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.

Enrollment: 1,750 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

5. 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

6. 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

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,750 participants in 8 patient groups

NYHA II Treatment Arm

Experimental group

Description:

All subjects will receive the Cordella Sensor. Clinicians will manage the subjects to target PAP per protocols specific Treatment Guidelines and according to Guideline-Directed Medical Therapy.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA II Active Control Arm

Experimental group

Description:

All subjects will receive the Cordella Sensor. Clinicians will manage subjects using the subjects daily data trends (BP, weight, HR, SpO2 symptoms) according to Guideline Directed Medical Therapy. Once the primary endpoint (24 months) is met, subjects and clinicians will be unblinded to PAP.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA II Crossover Arm

Experimental group

Description:

All subjects will receive the Cordella Sensor. At least 12 months following implant and following an adjudicated HFH, subjects in the Active Control Arm can qualify to crossover to the Crossover Arm and both patients and clinicians would then be unmasked to PAP. Clinicians will then manage the subjects to target PAP per protocols specific Treatment Guidelines and according to Guideline-Directed Medical Therapy.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA III Phase I Treatment Arm

Experimental group

Description:

All subjects will receive the Cordella Sensor. Clinicians will manage the subjects to target PAP per protocols specific Treatment Guidelines and according to Guideline-Directed Medical Therapy.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA III Phase I Active Control Arm

Experimental group

Description:

All subjects will receive the Cordella Sensor. Clinicians will manage subjects using the subjects daily data trends (BP, weight, HR, SpO2 symptoms) according to Guideline Directed Medical Therapy. Once the primary endpoint (6 months) is met, subjects and clinicians will be unblinded to PAP.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA III Clinician-Directed Patient Self-Management Arm (randomized)

Experimental group

Description:

This is Phase II / Randomization #2 following implant provided patient meets eligiibity criteria. Subjects will be instructed to take their PAP measurements daily in addition to their weight, BP, SpO2, and HR. All data, including PAP, will be visible to the patient. Subjects will manage their diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines. Clinicians will oversee the patient self-management to target PAP per protocol specific Treatment Guidelines and according to Guideline-Directed Medical Therapy.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA III Clinician Management Arm (randomized)

Experimental group

Description:

This is Phase II / Randomization #2 following implant provided patient meets eligiibity criteria. Subjects will be instructed to take their PAP measurements daily in addition to their weight, BP, SpO2, and HR. All data, including PAP, will be visible to the patient. Subjects will manage their diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines. Clinicians will manage the patients to target PAP per protocols specific to Treatment Guidelines and according to Guideline Directed Medical Therapy.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System

NYHA III Clinician Management Arm (Not randomized)

Experimental group

Description:

Subject will not be randomized if they do not meet eligibility criteria to potentially be randomized to Clinician-Directed Patient Self-Management. Subjects will be instructed to take their PAP measurements daily in addition to their weight, BP, SpO2, and HR. All data, including PAP, will be visible to the patient. Subjects will manage their diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines. Clinicians will manage the patients to target PAP per protocols specific to Treatment Guidelines and according to Guideline Directed Medical Therapy.

Treatment:

Device: Cordella™ Pulmonary Artery Sensor System