Clinical Evaluation of the AccuCinch® Ventricular Restoration System in Patients Who Present With Symptomatic Heart Failure With Reduced Ejection Fraction (HFrEF): The CORCINCH-HF Study

Study Overview
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Brief Summary
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Prospective, randomized, open-label, international, multi-center clinical study to evaluate the safety and efficacy of the AccuCinch Ventricular Restoration System in patients with heart failure and reduced ejection fraction (HFrEF).

Detailed Description
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The CORCINCH-HF Study is a prospective, randomized, open-label, multicenter, international, clinical safety and efficacy investigation of the AccuCinch Ventricular Restoration System. Subjects will be randomized in a 1:1 ratio: Treatment group: AccuCinch Ventricular Restoration System plus guideline-directed medical therapy (GDMT) (n 200) Control group: Guideline-directed medical therapy (GDMT) (n 200)

Official Title
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Randomized Clinical Evaluation of the AccuCinch® Ventricular Restoration System in Patients Who Present With Symptomatic Heart Failure With Reduced Ejection Fraction (HFrEF): The CORCINCH-HF Study

Conditions
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Heart Failure With Reduced Ejection Fraction (HFrEF), Dilated Cardiomyopathy

Intervention / Treatment
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* Device: AccuCinch Ventricular Restoration System
* Drug: Guideline-Directed Medical Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-years or older Ejection Fraction: ≥20% and ≤40% measured by transthoracic echocardiography (TTE) and assessed by an echocardiography (echo) core lab LV end-diastolic diameter ≥55 mm measured by TTE and assessed by an echo core lab Symptom Status: NYHA III, NYHA ambulatory IV, or NYHA II with a heart failure hospitalization within the prior 12 months (of signing the consent) Able to complete six-minute walk test with distance between 100 m and 450 m. Diagnosis and treatment for heart failure should be established at least 90 days before the date of consent. Subjects should be on stable, optimally titrated medical therapy for at least 30 days, as recommended according to current guidelines as standard-of-care for Heart Failure therapy, with any intolerance documented. Stable is defined as no more than a 100% increase or a 50% decrease of total daily doses. Medication changes within this range do not require any additional waiting before the screening assessments When a total daily dose increase or decrease exceeds that which is considered stable, the screening TTE and CT will be postponed 30 days after the medication change When additional titration is required to optimize a subject's medication that exceeds what is considered stable, the screening TTE and CT will be postponed at least 30 days after achieving the optimal dose (provided the optimal dose remains outside of the stable parameters) When a dose-for-dose equivalent change in the class of medication change is made, no additional waiting is required before the screening assessments When a change in class medication change exceeds what is considered stable, OR a new class of medication is added, the screening TTE and CT will be postponed 30 days after the medication change If an SGLT2 inhibitor is added to a subject's medications, the screening TTE and CT will be postponed at least 30 days after the addition If an SGLT2 inhibitor dose changes per the stable definition above, no additional waiting is required before the screening assessments If an SGLT2 inhibitor dose change exceeds what is considered stable, the screening TTE and CT will be postponed at least 30 days after achieving the optimal dose (provided the dose remains outside of the stable parameters) When applicable, for guideline-directed device-based therapies: a CRT device must be placed > 90 days before the screening TTE and CT, and an ICD must be placed > 30 days before the screening TTE and CT Able and willing to complete all qualifying diagnostic and functional tests, willing to accept blood product transfusion if required and agrees to comply with study follow-up schedule Exclusion Criteria: Cardiovascular Myocardial infarction or any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 90 days prior to consent Untreated clinically significant coronary artery disease (CAD) requiring revascularization Fluoroscopic or echocardiographic evidence of severe aortic arch calcification, mobile aortic atheroma, intracardiac mass, thrombus or vegetation Suboptimal ventricular anatomy or wall thickness as determined from screening echocardiography and/or CT scan Heart failure on the basis other than ischemic or non-ischemic dilated cardiomyopathy (e.g., hypertrophic cardiomyopathy, amyloid cardiomyopathy, restrictive cardiomyopathy, uncorrected congenital heart disease, constrictive pericarditis) Hemodynamic instability within 30 days prior to the implant defined as subject requiring inotropic support or mechanical hemodynamic support Any planned cardiac surgery or interventions within the next 180 days post-randomization (including therapeutic right heart procedures) Active bacterial endocarditis Severe RV dysfunction assessed by right heart catheterization (RHC) and/or TTE Fixed pulmonary hypertension with PA systolic pressure >70 mmHg not responsive to vasodilator therapy History of any stroke within the prior 90 days of consent or documented Modified Rankin Scale ≥ 2 disability from any prior stroke Valvular Mitral regurgitation grade 3+ (moderate-severe) or 4+ (severe) Untreated degenerative (primary) mitral valve disease (mild prolapse with no need for intervention is allowable) Prior mitral or aortic valve replacement Tricuspid regurgitation grade 4+ (severe) Moderate or severe aortic valve stenosis (AVA less than 1.5 cm2 or peak velocity AV Vmax >300 cm/sec) Aortic regurgitation grade 2+ (moderate), 3+ (moderate-severe), or 4+ (severe) Procedural Anatomical pathology or constraints preventing appropriate access/implant of the AccuCinch Ventricular Restoration System (e.g., femoral arteries will not support a 20F Introducer sheath) Renal insufficiency (i.e., eGFR of <25 ml/min/1.73 m2) Subjects in whom anticoagulation during the procedure is contraindicated Subjects in whom 90 days of antiplatelet therapy is contraindicated Known allergy to nitinol, polyester, or polyethylene Any prior true anaphylactic reaction to contrast agents; defined as known anaphylactoid or other non-anaphylactic allergic reactions to contrast agents that cannot be adequately pre-medicated prior to the index procedure General Life expectancy <1 year due to non-cardiac conditions Currently participating in another interventional investigational study Subjects on high dose steroids or immunosuppressant therapy Female subjects who are pregnant, of child-bearing potential without a documented birth control method, or who are lactating

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Device group: AccuCinch Ventricular Restoration System<br>Subjects in this arm will receive the AccuCinch Ventricular Restoration System | Device: AccuCinch Ventricular Restoration System<br>* AccuCinch Ventricular Restoration System<br>|
| Active Comparator: Control group: Guideline-Directed Medical Therapy<br>Subjects in this arm will receive guideline-directed medical therapy (GDMT) | Drug: Guideline-Directed Medical Therapy<br>* Guideline-Directed Medical Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from device- or femoral artery access-related major adverse events (MAE) | MAE defined as: All-cause death, Myocardial infarction, Stroke, Need for non-elective cardiovascular surgery, Worsening of heart-failure requiring mechanical circulatory support for more than 24 hours Acute kidney injury requiring renal replacement therapy | 180 days | 
| Change from baseline in Kansas City Cardiomyopathy Questionnaire Quality of Life Questionnaire (KCCQ) Score | Higher scores in the KCCQ reflect better health status | 180 days | 
| 6-Minute Walk Test (6MWT) distance (m) | Change in 6MWT distance (m) from baseline | 180 days | 
| Freedom from device- or femoral artery access-related major adverse events (MAE) | MAE defined as: All-cause death, Myocardial infarction, Stroke, Need for non-elective cardiovascular surgery, Worsening of heart-failure requiring mechanical circulatory support for more than 24 hours Acute kidney injury requiring renal replacement therapy | 365 days | 
| A hierarchical composite endpoint of all-cause deaths, left ventricular assist device (LVAD) implants or heart transplants, heart failure hospitalizations, and changes from baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) | A hierarchical composite endpoint of number of all-cause deaths, number of left ventricular assist device (LVAD) implants or heart transplants, number of heart failure hospitalizations, and change from baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS), evaluated using the Win Ratio method | 365 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of all-cause deaths or all-cause hospitalizations |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Number of all-cause deaths |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Number of all-cause hospitalizations |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Incidence of all serious adverse events, including device- and procedure- related complications |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Changes from baseline in New York Heart Association (NYHA) functional class |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Changes from baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS) | Higher scores in the KCCQ reflect better health status | 30 days, 90 days, 365 days, 545 days, 730 days | 
| Changes from baseline in 6-Minute Walk Test (6MWT) | Measure in meters | 30 days, 90 days, 365 days, 545 days, 730 days | 
| Changes in left ventricular ejection fraction (LVEF) from baseline and from post-procedure/pre-hospital discharge as assessed by echo |  | 30 days, 90 days, 365 days, 730 days | 
| Changes in left ventricular ejection fraction (LVEF) from baseline and from post-procedure/pre-hospital discharge as assessed by echo and CT |  | 180 days | 
| Changes in left ventricular end-diastolic volume (LVEDV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo |  | 30 days, 90 days, 365 days, 730 days | 
| Changes in left ventricular end-diastolic volume (LVEDV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo and CT |  | 180 days | 
| Changes in left ventricular end-systolic volume (LVESV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo |  | 30 days, 90 days, 365 days, 730 days | 
| Changes in left ventricular end-systolic volume (LVESV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo and CT |  | 180 days | 
| Rate and number of cardiovascular death events |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Rate and number of heart failure death events |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 
| Rate and number of heart failure-related hospitalizations |  | 30 days, 90 days, 180 days, 365 days, 545 days, 730 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Reduced Ejection Fraction, Cardiomyopathy