Clinical trial NCT04331769: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)
Dilated Cardiomyopathy
Keywords: Heart Failure
Reduced Ejection Fraction
Cardiomyopathy
Lead sponsor: Ancora Heart, Inc.
Sponsor class: INDUSTRY
First posted: 2020-04-02
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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: 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:

1. Treatment group: AccuCinch Ventricular Restoration System plus guideline-directed medical therapy (GDMT) (n\~200)
2. Control group: Guideline-directed medical therapy (GDMT) (n\~200)

Eligibility criteria: Inclusion Criteria:

1. Age 18-years or older
2. Ejection Fraction: ≥20% and ≤40% measured by transthoracic echocardiography (TTE) and assessed by an echocardiography (echo) core lab
3. LV end-diastolic diameter ≥55 mm measured by TTE and assessed by an echo core lab
4. Symptom Status:

   1. NYHA III,
   2. NYHA ambulatory IV, or
   3. NYHA II with a heart failure hospitalization within the prior 12 months (of signing the consent)
5. Able to complete six-minute walk test with distance between 100 m and 450 m.
6. 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.

   1. "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
   2. 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
   3. 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)
   4. When a dose-for-dose equivalent change in the class of medication change is made, no additional waiting is required before the screening assessments
   5. 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
   6. 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
   7. If an SGLT2 inhibitor dose changes per the stable definition above, no additional waiting is required before the screening assessments
   8. 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)
   9. 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
7. 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

1. Myocardial infarction or any percutaneous cardiovascular intervention, cardiovascular surgery, or carotid surgery within 90 days prior to consent
2. Untreated clinically significant coronary artery disease (CAD) requiring revascularization
3. Fluoroscopic or echocardiographic evidence of severe aortic arch calcification, mobile aortic atheroma, intracardiac mass, thrombus or vegetation
4. Suboptimal ventricular anatomy or wall thickness as determined from screening echocardiography and/or CT scan
5. 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)
6. Hemodynamic instability within 30 days prior to the implant defined as subject requiring inotropic support or mechanical hemodynamic support
7. Any planned cardiac surgery or interventions within the next 180 days post-randomization (including therapeutic right heart procedures)
8. Active bacterial endocarditis
9. Severe RV dysfunction assessed by right heart catheterization (RHC) and/or TTE
10. Fixed pulmonary hypertension with PA systolic pressure \>70 mmHg not responsive to vasodilator therapy
11. History of any stroke within the prior 90 days of consent or documented Modified Rankin Scale ≥ 2 disability from any prior stroke

    Valvular
12. Mitral regurgitation grade 3+ (moderate-severe) or 4+ (severe)
13. Untreated degenerative (primary) mitral valve disease (mild prolapse with no need for intervention is allowable)
14. Prior mitral or aortic valve replacement
15. Tricuspid regurgitation grade 4+ (severe)
16. Moderate or severe aortic valve stenosis (AVA less than 1.5 cm2 or peak velocity AV Vmax \>300 cm/sec)
17. Aortic regurgitation grade 2+ (moderate), 3+ (moderate-severe), or 4+ (severe)

    Procedural
18. 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)
19. Renal insufficiency (i.e., eGFR of \<25 ml/min/1.73 m2)
20. Subjects in whom anticoagulation during the procedure is contraindicated
21. Subjects in whom 90 days of antiplatelet therapy is contraindicated
22. Known allergy to nitinol, polyester, or polyethylene
23. 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
24. Life expectancy \<1 year due to non-cardiac conditions
25. Currently participating in another interventional investigational study
26. Subjects on high dose steroids or immunosuppressant therapy
27. Female subjects who are pregnant, of child-bearing potential without a documented birth control method, or who are lactating

Primary outcomes:
measure: Freedom from device- or femoral artery access-related major adverse events (MAE)
timeFrame: 180 days
measure: Change from baseline in Kansas City Cardiomyopathy Questionnaire Quality of Life Questionnaire (KCCQ) Score
timeFrame: 180 days
measure: 6-Minute Walk Test (6MWT) distance (m)
timeFrame: 180 days
measure: Freedom from device- or femoral artery access-related major adverse events (MAE)
timeFrame: 365 days
measure: 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)
timeFrame: 365 days
Secondary outcomes:
measure: Number of all-cause deaths or all-cause hospitalizations
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Number of all-cause deaths
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Number of all-cause hospitalizations
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Incidence of all serious adverse events, including device- and procedure- related complications
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Changes from baseline in New York Heart Association (NYHA) functional class
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Changes from baseline in Kansas City Cardiomyopathy Questionnaire Overall Score (KCCQ-OS)
timeFrame: 30 days, 90 days, 365 days, 545 days, 730 days
measure: Changes from baseline in 6-Minute Walk Test (6MWT)
timeFrame: 30 days, 90 days, 365 days, 545 days, 730 days
measure: Changes in left ventricular ejection fraction (LVEF) from baseline and from post-procedure/pre-hospital discharge as assessed by echo
timeFrame: 30 days, 90 days, 365 days, 730 days
measure: Changes in left ventricular ejection fraction (LVEF) from baseline and from post-procedure/pre-hospital discharge as assessed by echo and CT
timeFrame: 180 days
measure: Changes in left ventricular end-diastolic volume (LVEDV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo
timeFrame: 30 days, 90 days, 365 days, 730 days
measure: Changes in left ventricular end-diastolic volume (LVEDV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo and CT
timeFrame: 180 days
measure: Changes in left ventricular end-systolic volume (LVESV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo
timeFrame: 30 days, 90 days, 365 days, 730 days
measure: Changes in left ventricular end-systolic volume (LVESV) from baseline and from post-procedure/pre-hospital discharge as assessed by echo and CT
timeFrame: 180 days
measure: Rate and number of cardiovascular death events
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Rate and number of heart failure death events
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Rate and number of heart failure-related hospitalizations
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
Other outcomes:
measure: Changes from baseline in mitral effective regurgitant orifice area (EROA)
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
measure: Changes from baseline in left atrial strain measured by Echo
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
measure: Changes from baseline in left ventricular global longitudinal strain measured by Echo
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
measure: Changes from baseline in right ventricular free wall longitudinal strain measured by Echo
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
measure: Changes from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) individual domains
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Changes from baseline in EuroQol Five Dimension Five Level (EQ-5D-5L) Quality of Life Questionnaire
timeFrame: 30 days, 90 days, 180 days, 365 days, 545 days, 730 days
measure: Changes from baseline in right ventricular (RV) fractional area change measured by Echo
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
measure: Changes from baseline in tricuspid annular plane systolic excursion (TAPSE) measured by Echo
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
measure: Changes from baseline in tricuspid regurgitation measured by Echo
timeFrame: 30 days, 90 days, 180 days, 365 days, 730 days
Locations:
city: Birmingham
country: United States
facility: Grandview Medical Group Research, LLC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Dignity Health St. Joseph's Hospital and Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Phoenix Cardiovascular Research Group
state: Arizona
city: Tucson
country: United States
facility: Tucson Medical Center
state: Arizona
city: Little Rock
country: United States
facility: Baptist Health Heart Failure & Transplant Institute
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Hartford
country: United States
facility: Hartford Health
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Washington
country: United States
facility: Medstar Health Research Institute
state: District of Columbia
city: Atlantis
country: United States
facility: JFK Medical Center
state: Florida
city: Largo
country: United States
facility: HCA Florida Largo Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Pensacola
country: United States
facility: Ascension Sacred Heart
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Heart Institute
state: Georgia
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Downers Grove
country: United States
facility: Advocate Good Samaritan Hospital
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Cardiovascular Research Institute of Kansas
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Heart Specialists
state: Kentucky
city: Baton Rouge
country: United States
facility: Our Lady of the Lake Regional Medical Center
state: Louisiana
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Bangor
country: United States
facility: Northern Light Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Southfield
country: United States
facility: Ascension Providence Hospital
state: Michigan
city: Coon Rapids
country: United States
facility: Metropolitan Heart and Vascular Institute & Mercy Hosp
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: Jackson Heart Clinic
state: Mississippi
city: St. Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Browns Mills
country: United States
facility: Deborah Heart & Lung
state: New Jersey
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Robert Wood Johnson Medical School
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Heart Institute
state: New Mexico
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: CUMC/New York Presbyterian Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine-New York Presbyterian Hospital
state: New York
city: Poughkeepsie
country: United States
facility: Vassar Brothers Medical Center
state: New York
city: Roslyn
country: United States
facility: St. Francis Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart and Vascular Research, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: The Christ Hospital
state: Ohio
city: Cleveland
country: United States
facility: UH Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Harrisburg
country: United States
facility: Pinnacle Health Cardiovascular Institute
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Heart and Vascular Institute
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Prisma Health
state: South Carolina
city: Knoxville
country: United States
facility: Tennova Healthcare-Turkey Creek Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Ascension Saint Thomas
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Ascension Texas Cardiovascular
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Houston
country: United States
facility: Houston Heart
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine St. Luke's Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Houston
country: United States
facility: UT Health
state: Texas
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
city: Plano
country: United States
facility: Baylor Scott & White
state: Texas
city: San Antonio
country: United States
facility: Methodist Healthcare System, San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Intermountain Medical Center
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: CJW Chippenham Medical Center
state: Virginia
city: Richmond
country: United States
facility: Bon Secours St Mary's Hospital
state: Virginia
city: Roanoke
country: United States
facility: Carilion Roanoke Memorial Hospital
state: Virginia
city: Winchester
country: United States
facility: Valley Health Winchester
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Spokane
country: United States
facility: Providence Sacred Heart Medical Center
state: Washington
city: Charleston
country: United States
facility: Charleston Area Medical Center
state: West Virginia
city: Milwaukee
country: United States
facility: Aurora St. Luke's Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Minsk
country: Belarus
facility: Republican Scientific and Practical Centre of Cardiology
city: Aalst
country: Belgium
facility: OLV Heart Centre
city: Brugge
country: Belgium
facility: AZ Sint-Jan-Oostende AV Campus Brugge
city: Brno
country: Czechia
facility: St. Anne's University Hospital
city: Prague
country: Czechia
facility: Na Homolce Hospital
city: Marseille
country: France
facility: Hôpital de la Timone
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Toulouse
country: France
facility: Clinique-Pasteur
city: Bernau
country: Germany
facility: Immanuel Klinikum Bernau Herzzentrum Brandenburg Universitätsklinikum der Medizinischen Hochschule Brandenburg
city: Frankfurt
country: Germany
facility: CardioVasculäres Centrum
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Hamburg
country: Germany
facility: Universitäres Herz- und Gefäßzentrum Hamburg
city: Köln
country: Germany
facility: Universitätsklinikum Köln (AöR)
city: Athens
country: Greece
facility: Hygeia Hospital
city: Kallithéa
country: Greece
facility: Onassis Cardiac Surgery Center
city: Thessaloniki
country: Greece
facility: Interbalkan Medical Hospital of Thessaloniki
city: Milano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
state: Lombardy
city: Catania
country: Italy
facility: A O U Policlinico G. Rodolico - San Marco
city: Milano
country: Italy
facility: Centro Cardiologico Monzino S.p.a
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Belgrade
country: Serbia
facility: Institute of Cardiovascular Diseases of Vojvodina
city: Belgrade
country: Serbia
facility: Institute of Cardiovascular Diseases
city: Belgrade
country: Serbia
facility: University Clinical Centre of Serbia
city: Niš
country: Serbia
facility: University Clinical Center Niš
Study officials:
affiliation: Columbia University
name: Martin B Leon, MD
role: STUDY_CHAIR
affiliation: Montefiore Medical Center/Albert Einstein College of Medicine
name: Ulrich P Jorde, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Presbyterian/Weill Cornell Medicine
name: Mark Reisman, MD
role: PRINCIPAL_INVESTIGATOR
References: