PROACTIVE-HF-2 Trial Heart Failure NYHA Class II and III
- Conditions
- Heart Failure NYHA Class IIHeart FailureHeart Failure NYHA Class III
- Interventions
- Device: Cordella™ Pulmonary Artery Sensor System
- Registration Number
- NCT05934487
- Lead Sponsor
- Endotronix, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1750
Not provided
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Randomized Arm- Treatment Arm Cordella™ Pulmonary Artery Sensor System 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. Randomized Arm- Active Control Arm Cordella™ Pulmonary Artery Sensor System 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. Single Arm- Clinician-Directed Patient Self-Management Arm Cordella™ Pulmonary Artery Sensor System All subjects will receive the Cordella Sensor. Subjects will self-manage their Loop diuretics per protocol specific Clinician-Directed Patient Self-Management Treatment Guidelines and Clinicians will manage the patients according to Guideline-Directed Medical Therapy. Randomized Arm- Crossover Arm Cordella™ Pulmonary Artery Sensor System 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. Single Arm- Clinician Management Arm Cordella™ Pulmonary Artery Sensor System 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.
- Primary Outcome Measures
Name Time Method Safety- Single Arm- Freedom from pressure sensor failure 12 months Freedom from pressure sensor failure at 12 months
Efficacy- NYHA II Cohort - A composite of first HF event or death from Cardiovascular Death up to 24 months. 24 months A composite endpoint of first HF event or death from CVD up to 24 months.
Efficacy- NYHA III Cohort (Phase I) - a composite of HF events or death from cardiovascular disease at 6 months 12 months A composite of HF events or death from cardiovascular disease at 6 months
Safety- Randomized Arm- Freedom from device/system related complication 24 months Freedom from device/system related complication at 24 months
Safety- Randomized Arm-Freedom from pressure sensor failure 24 months Freedom from pressure sensor failure at 24 months
Safety- Single Arm-Freedom from device/system related complication 12 months Freedom from device/system related complication at 12 months
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 12 months 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
- Secondary Outcome Measures
Name Time Method Efficacy - NYHA II Cohort & NYHA III Cohort - Death from cardiovascular disease Duration of study (to 5 years) Death from cardiovascular disease
Efficacy - NYHA II Cohort & NYHA III Cohort - HF Hospitalizations Duration of study (to 5 years) Length of stay
Efficacy - NYHA II Cohort & NYHA III Cohort- HF Hospitalizations 12 months and 24 months -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
Efficacy - NYHA II Cohort & NYHA III Cohort - All-cause mortality Duration of study (to 5 years) All-cause mortality
Efficacy - NYHA II Cohort & NYHA III Cohort - Urgent HF visits Duration of study (to 5 years) Urgent HF visits
Efficacy - NYHA II Cohort - Incidence of HF hospitalizations or all-cause mortality 12 months Incidence of HF hospitalizations or all-cause mortality
Efficacy - NYHA III Cohort - Composite of first HF event (HF hospitalization or urgent HF visit or death from cardiovascular disease (CVD) Up to 24 months Composite of first HF event (HF hospitalization or urgent HF visit or
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 Duration of study (to 5 years) -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
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. Duration of study (to 5 years) Various measurements via ECHO and evaluated by ECHO core lab at Baseline, 12, 24, 36, 48 and 60 months.
Efficacy - NYHA II Cohort & NYHA III Cohort - Heart failure related medication changes Duration of study (to 5 years) Heart failure related medication changes
Efficacy - NYHA II Cohort & NYHA III Cohort - Change in PAP from baseline Duration of study (to 5 years) Change in PAP from baseline
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 Duration of study (to 5 years) 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
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) Duration of study (to 5 years) Patient Outcome Measures as measured by KCCQ, Brief Illness Perception Questionnaire, and EuroQol-5 Dimensions-5 Level (EQ-5D-5L)
Efficacy - NYHA II Cohort & NYHA III Cohort - Functional status improvement as measured by NYHA classification and 6MWT Duration of study (to 5 years) Functional status improvement as measured by NYHA classification and 6MWT
Efficacy - NYHA II Cohort & NYHA III Cohort - Health Economic Analysis Duration of study (to 5 years) Health Economic Analysis
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 Duration of study (to 5 years) HFH stratified by ejection fraction (HFrEF,
Efficacy - NYHA II Cohort & NYHA III Cohort - Mortality by baseline EF (HFrEF, HFmrEF, HFpEF, HF recovered EF), and baseline enrollmentECHO estimated systolic PAP Duration of study (to 5 years) Mortality by baseline EF (HFrEF, HFmrEF,
Efficacy - NYHA II Cohort & NYHA III Cohort - Days alive outside hospital (DAOH) Duration of study (to 5 years) Days alive outside hospital (DAOH)
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 Duration of study (to 5 years) Adherence to regular PAP and vital sign measurements including a sub-analysis on subjects who move to another area of the country
Safety - NYHA II Cohort - Freedom from device/system related complications at 12 months Duration of study (to 5 years) Freedom from device/system related complications at 12 months
Safety - NYHA III Cohort - Freedom from pressure sensor failure at 12 months Duration of study (to 5 years) Freedom from pressure sensor failure at 12 months
Safety - NYHA II Cohort & NYHA III Cohort - Pressure sensor failure rate throughout the study Duration of study (to 5 years) Pressure sensor failure rate throughout the study
Safety - NYHA II Cohort & NYHA III Cohort - Frequency of serious adverse events throughout the study Duration of study (to 5 years) Frequency of serious adverse events throughout the study
Safety - NYHA II Cohort & NYHA III Cohort - Frequency of implant procedure and procedure related adverse events and serious adverse events Duration of study (to 5 years) Frequency of implant procedure and procedure related adverse events and serious adverse events
Safety - NYHA III Cohort - Freedom from device/system related complications at 24 months Duration of study (to 5 years) Freedom from device/system related complications at 24 months
Safety - NYHA III Cohort - Freedom from pressure sensor failure at 24 months Duration of study (to 5 years) Freedom from pressure sensor failure at 24 months
Trial Locations
- Locations (46)
Beth Israel Deaconess Medical Center (BIDMC)
🇺🇸Boston, Massachusetts, United States
Centra Care Heart Center
🇺🇸St. Cloud, Minnesota, United States
St. Lukes/ Mid-American Heart Institute
🇺🇸Kansas City, Missouri, United States
Stony Brook University Med Center
🇺🇸Stony Brook, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Heart Care Centers of Illinois (HCCI)
🇺🇸Palos Park, Illinois, United States
Ascension St. Vincent's
🇺🇸Indianapolis, Indiana, United States
Minneapolis Heart Institute Foundation
🇺🇸Minneapolis, Minnesota, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
MedStar
🇺🇸Baltimore, Maryland, United States
Tufts Medical Center
🇺🇸Boston, Massachusetts, United States
Ascension Providence Hospital Cardiology - Heart Cardiology
🇺🇸Howell, Michigan, United States
Mount Sinai West
🇺🇸New York, New York, United States
Lenox Hill/ Northwell Health
🇺🇸New York, New York, United States
West Virginia University
🇺🇸Morgantown, West Virginia, United States
Advocate Aurora St. Luke's
🇺🇸Milwaukee, Wisconsin, United States
St. Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
USC
🇺🇸Los Angeles, California, United States
Baptist Health South Florida
🇺🇸Miami, Florida, United States
Piedmont
🇺🇸Atlanta, Georgia, United States
Advocate Health System
🇺🇸Downers Grove, Illinois, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Mount Sinai
🇺🇸New York, New York, United States
The Christ Hospital- Cincinnati
🇺🇸Cincinnati, Ohio, United States
Ascension Sacred Heart
🇺🇸Pensacola, Florida, United States
University of Kansas Medical Center (KUMC)
🇺🇸Kansas City, Kansas, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Penn State Health
🇺🇸Hershey, Pennsylvania, United States
PRISMA Health- Upstate
🇺🇸Greenville, South Carolina, United States
Sanford
🇺🇸Sioux Falls, South Dakota, United States
Austin Heart
🇺🇸Austin, Texas, United States
Providence Everett
🇺🇸Everett, Washington, United States
Methodist San Antonio
🇺🇸San Antonio, Texas, United States
University Hospital (Cleveland)
🇺🇸Cleveland, Ohio, United States
Medical City Healthcare Dallas
🇺🇸Dallas, Texas, United States
Baylor Scott & White -Dallas
🇺🇸Fort Worth, Texas, United States
Baylor/Texas Heart
🇺🇸Houston, Texas, United States
Baylor - Temple
🇺🇸Temple, Texas, United States
University of Vermont
🇺🇸Burlington, Vermont, United States
Providence St. Vincent's - Portland
🇺🇸Portland, Oregon, United States
Oregon Health Science Portland
🇺🇸Portland, Oregon, United States
University of Wisconsin
🇺🇸Madison, Wisconsin, United States
UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Vanderbilt
🇺🇸Nashville, Tennessee, United States