Assessment of CCM in HF With Higher Ejection Fraction
- Conditions
- Heart FailureHeart Failure With Preserved Ejection FractionHeart Failure With Mid Range Ejection FractionHeart Failure With Moderately Reduced Ejection FractionDiastolic Heart Failure
- Interventions
- Device: Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini SystemDevice: OPTIMIZER™ Smart Mini System
- Registration Number
- NCT05064709
- Lead Sponsor
- Impulse Dynamics
- Brief Summary
The AIM HIGHer Clinical Trial will evaluate the safety and efficacy of Cardiac Contractility Modulation (CCM) therapy in patients with heart failure with LVEF ≥40% and ≤70%.
- Detailed Description
The AIM HIGHer Clinical Trial is a prospective, multi-center, randomized, quadruple-blind, sham-controlled, two-part embedded trial of the safety and efficacy of CCM therapy delivered via the OPTIMIZER Smart Mini System in subjects with heart failure and an LVEF ≥40% and ≤70%. Subjects will be enrolled at approximately 150 sites in the US and 75 sites OUS.
All subjects will undergo screening and baseline testing; all eligible subjects will be implanted with the Optimizer System. Subjects will be randomized in a 2:1 ratio to either CCM ON (CCM group) or to CCM OFF (Sham group). The trial will be blinded to the treatment assignment of the device for 18-months. Subjects in the Sham group will have CCM turned ON after completion of the 18-month study visit. Subjects enrolled during Part I (450 subjects) of the trial will continue follow-up through the end of Part II (up to an additional 1,050) and contribute data to both parts of the trial. Each part of the trial is distinguished by a separate scientific purpose. The specific purpose of each part is:
Part I - Establish safety and effectiveness based on functional capacity and health status.
Part II - Establish safety and effectiveness based on clinical outcome data.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
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Signed and dated informed consent form;
-
Male or non-pregnant female, 18 years or older;
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Diagnosed with symptomatic heart failure;
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LVEF ≥40 and ≤70% (as assessed by site echo);
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A. Heart failure hospitalization within 12 months prior to study consent OR an urgent heart failure visit requiring IV therapy within 6 months prior to study consent OR B. If there is no heart failure hospitalization within 12 months prior to study consent OR an urgent heart failure visit requiring IV therapy within 6 months prior to study consent, an elevated BMI-adjusted natriuretic peptide value must be achieved (Refer to Table 1 in Section 9.2.6)
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Subjects must meet one of the following conditions:
- Have stable, scheduled oral loop diuretic treatment (not just PRN) for a minimum of 30 days before providing study consent unless there is a documented allergy or intolerance.
- Eligibility for enrollment is maintained for patients on an SGLT2 inhibitor without prescribed concurrent standing loop diuretic therapy if investigators provide instructions for a flexible PRN diuretic regimen (deemed appropriate by the clinician in response to symptoms or weight gain) Note: Stable is defined as no more than a 100% increase or 50% decrease in dose within the last 30 days. A one-time hold of diuretic dosing for 24 hours during the 30-day period is allowed and not an exclusionary event.
- Resting ventricular rate <50 or >110 bpm;
- Resting systolic blood pressure <100 or ≥160 mmHg;
- BMI greater than 46
- Any severe valvular stenotic disease or any severe valvular regurgitation;
- Mechanical tricuspid valve;
- Complex congenital heart disease;
- Exercise tolerance limited by a condition other than heart failure that, in the opinion of the investigator, contributes significantly to the primary symptoms of shortness of breath and/or exercise intolerance;
- Unable to walk at least 100 meters or walks more than 450 meters during a 6MWT;
- A KCCQ CCS score higher than 85;
- Hypertrophic, infiltrative/restrictive or inflammatory cardiomyopathy;
- Unstable angina pectoris within 30 days prior to study consent;
- Acute, decompensated heart failure requiring IV therapy or ultrafiltration within 30 days prior to consent, in the hospital or an outpatient setting;
- Receiving cardiac resynchronization therapy (CRT); NOTE: Subjects with active/ongoing cardiac resynchronization therapy (CRT) implanted more than one year ago are eligible for inclusion if they are currently classified as NYHA class III or higher.
- Scheduled for a cardiac surgery or a percutaneous cardiac intervention (PCI) or have undergone cardiac surgery within 90 days or a PCI procedure within 30 days prior to study consent;
- Myocardial infarction within 90 days prior to study consent;
- Prior heart transplant or ventricular assist device;
- Planning to become pregnant during the study;
- Dialysis (permanent) or GFR <15 ml/min/1.73m2;
- Participating in another investigational drug or device study that may interfere with the interpretation of study data;
- Currently undergoing active chemotherapeutic and/or radiation treatment for cancer or has a history of chemotherapy during the 2-year period prior to study consent;
- Expected lifespan of less than 18 months from time of study consent;
- Unable to follow through study protocol for any reasons in the investigator's judgement.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CCM Group (CCM ON) Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System CCM therapy will be turned on in 2/3 of the subjects for the entire duration of the study. Sham Group (CCM OFF) OPTIMIZER™ Smart Mini System CCM therapy will be turned off in 1/3 of the subjects for the first 18 months of the study. After 18 months, CCM therapy will be turned on for the rest of the study duration.
- Primary Outcome Measures
Name Time Method Part 1 Efficacy Endpoint - Change in 6-minute walk distance (6MWD) from baseline to 6 months. 6 months Demonstrate that CCM therapy improves functional capacity in subjects with symptomatic heart failure with LVEF ≥40% and ≤70%. Compare the changes in functional capacity, as measured by the 6-minute walk distance (6MWD), from baseline to 6-months following the randomization date between the two study groups.
Part 1 Efficacy Endpoint - Change in the health status from baseline to 6 months as assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS). 6 months Demonstrate that CCM therapy improves health status in subjects with symptomatic heart failure with LVEF ≥40% and ≤60%. Compare the changes in health status, as measured by the KCCQ CSS, from baseline to 6-months following the randomization date between the two study groups.
Part 1 Safety Endpoint - The incidence of Optimizer device- or procedure-related complications within the first 12 months after implant 12 months Compare the composite incidence of Optimizer device-related and procedure-related SAEs (complications) for available data collected from implant to 12 months after the Optimizer implantation procedure to a performance goal of 75% free of complications.
Part 2 Endpoint - The hierarchical composite of mortality, morbidity, and health status outcomes (KCCQ CSS). 18 months Demonstrate that CCM therapy improves a composite endpoint of cardiovascular mortality at 18-months, heart failure hospitalizations at 18-months, urgent heart failure visits requiring IV diuretics at 18-months and the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS) at 12-months. Comparison of a hierarchical composite endpoint between the two study groups will be based on the Finkelstein-Schoenfeld global rank method.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (103)
Grandview Medical Group Research, LLC
🇺🇸Birmingham, Alabama, United States
The University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
CardioVascular Associates of Mesa
🇺🇸Mesa, Arizona, United States
Chan Heart Rhythm Institute
🇺🇸Mesa, Arizona, United States
Southwest Cardiovascular Associates
🇺🇸Mesa, Arizona, United States
Banner Health- Phoenix
🇺🇸Phoenix, Arizona, United States
Arizona Heart Rhythm
🇺🇸Phoenix, Arizona, United States
Cardiovascular Consultants, Ltd
🇺🇸Phoenix, Arizona, United States
HonorHealth
🇺🇸Scottsdale, Arizona, United States
Pima Heart and Vascular
🇺🇸Tuscon, Arizona, United States
John Muir Health
🇺🇸Concord, California, United States
Northbay Heart and Vascular
🇺🇸Fairfield, California, United States
University of California San Diego
🇺🇸La Jolla, California, United States
USC Keck School of Medicine
🇺🇸Los Angeles, California, United States
Cedars Sinai Medical Center
🇺🇸Los Angeles, California, United States
Valley Clinical Trials Pasadena
🇺🇸Northridge, California, United States
Valley Clinical Trials- Northridge
🇺🇸Northridge, California, United States
Sequoia Hospital
🇺🇸Redwood City, California, United States
University of California Davis Health
🇺🇸Sacramento, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Hartford Healthcare
🇺🇸Hartford, Connecticut, United States
Nuvance Health
🇺🇸Wilton, Connecticut, United States
HCA Florida JFK Hospital
🇺🇸Atlantis, Florida, United States
Nouvelle Clinical Research LLC
🇺🇸Cutler Bay, Florida, United States
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
Broward Health
🇺🇸Fort Lauderdale, Florida, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
Baptist Health South Florida
🇺🇸Miami, Florida, United States
NCA Research Institute - Florida
🇺🇸Naples, Florida, United States
AdventHealth Orlando
🇺🇸Orlando, Florida, United States
Revival Clinical Research
🇺🇸Orlando, Florida, United States
Tallahassee Research Institute
🇺🇸Tallahassee, Florida, United States
Cleveland Clinic Foundation - Florida Weston Hospital
🇺🇸Weston, Florida, United States
Piedmont Healthcare
🇺🇸Atlanta, Georgia, United States
WellStar Health System, Inc
🇺🇸Marietta, Georgia, United States
Franciscan Health Indianapolis
🇺🇸Indianapolis, Indiana, United States
Ascension Medical Group St. Vincent
🇺🇸Indianapolis, Indiana, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
MercyOne Iowa Heart
🇺🇸West Des Moines, Iowa, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Kansas City Cardiac Arrhythmia Research LLC
🇺🇸Overland Park, Kansas, United States
Baptist Health Lexington
🇺🇸Lexington, Kentucky, United States
University of Kentucky Research Foundation
🇺🇸Lexington, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Ascension St. John
🇺🇸Detroit, Michigan, United States
Ascension Providence Hospital
🇺🇸Southfield, Michigan, United States
Trinity health- Michigan Heart
🇺🇸Ypsilanti, Michigan, United States
Minneapolis Heart Institute at Abbott Northwestern Hospital
🇺🇸Minneapolis, Minnesota, United States
North Mississippi Medical Center
🇺🇸Tupelo, Mississippi, United States
Our Lady of Lourdes
🇺🇸Camden, New Jersey, United States
Sanger Heart and Vascular
🇺🇸Charlotte, North Carolina, United States
TriHealth Bethesda
🇺🇸Cincinnati, Ohio, United States
St. Louis Heart and Vascular
🇺🇸Bridgeton, Missouri, United States
St. Lukes Hospital Kansas City (Mid America Heart Institute)
🇺🇸Kansas City, Missouri, United States
Bryan Heart
🇺🇸Lincoln, Nebraska, United States
Catholic Medical Center
🇺🇸Manchester, New Hampshire, United States
Jersey Shore University Medical Center
🇺🇸Edison, New Jersey, United States
St. Luke's Hospital
🇺🇸Chesterfield, Missouri, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Hackensack University Medical Center
🇺🇸Edison, New Jersey, United States
Cooper Hospital- Cardiovascular Associates of Delaware Valley
🇺🇸Haddon Heights, New Jersey, United States
Atlantic Health System- Morristown Medical Center
🇺🇸Morristown, New Jersey, United States
Rutgers New Jersey Medical School
🇺🇸Piscataway, New Jersey, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
OhioHealth Research Institute
🇺🇸Columbus, Ohio, United States
Mercy Health- St. Vincent Medical Center LLC
🇺🇸Toledo, Ohio, United States
Oklahoma Heart Institute
🇺🇸Tulsa, Oklahoma, United States
St. Francis Hospital - Tulsa
🇺🇸Tulsa, Oklahoma, United States
Providence Heart & Vascular
🇺🇸Portland, Oregon, United States
Bryn Mawr Medical Specialists Association
🇺🇸Bryn Mawr, Pennsylvania, United States
UPMC Pinnacle Harrisburg
🇺🇸Harrisburg, Pennsylvania, United States
Penn State Hershey Medical City
🇺🇸Hershey, Pennsylvania, United States
Lancaster General Hospital
🇺🇸Lancaster, Pennsylvania, United States
Penn Presbyterian Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Hospital of the University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Tower Health Reading Hospital
🇺🇸Reading, Pennsylvania, United States
WellSpan Health
🇺🇸York, Pennsylvania, United States
Prisma Health Upstate
🇺🇸Greenville, South Carolina, United States
The Stern Cardiovascular Foundation
🇺🇸Germantown, Tennessee, United States
Texas Cardiac Arrhythmia Research Foundation
🇺🇸Austin, Texas, United States
Ascension Seton
🇺🇸Austin, Texas, United States
Austin Heart
🇺🇸Austin, Texas, United States
Baylor Scott and White Research Institute
🇺🇸Dallas, Texas, United States
HCA Medical City Dallas
🇺🇸Dallas, Texas, United States
Baylor Scott White- All Saints- Fort Worth
🇺🇸Fort Worth, Texas, United States
Medical City Fort Worth Hospital
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Houston Methodist
🇺🇸Houston, Texas, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
Heart Rhythm Specialists
🇺🇸McKinney, Texas, United States
Baylor Scott and White- The Heart Hospital- Plano
🇺🇸Plano, Texas, United States
Baylor Scott and White Research Institute - Round Rock
🇺🇸Round Rock, Texas, United States
Methodist Hospital
🇺🇸San Antonio, Texas, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Peace Health
🇺🇸Vancouver, Washington, United States