Assessment of CCM in HF With Higher Ejection Fraction

NCT05064709 | Recruiting DMC FDA Device

• 1 other identifier: CA_CP_340
• Study Type: interventional
• Target: 1,500
• Locations: 1 country
• Sites: 105

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%.

Conditions

Heart Failure; Heart Failure With Moderately Reduced Ejection Fraction; Diastolic Heart Failure; Heart Failure With Preserved Ejection Fraction; Heart Failure With Mid Range Ejection Fraction

Keywords

HFpEF; Heart failure; CCM; CCM therapy; cardiac contractility modulation; symptomatic heart failure; left ventricular ejection fraction; LVEF; Optimizer; Optimizer Smart Mini; Quality of Life

Outcome Measures

Primary Outcomes (4)

• Part 1 Efficacy Endpoint - Change in 6-minute walk distance (6MWD) from baseline to 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.

  6 months

• 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).

  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.

  6 months

• Part 1 Safety Endpoint - The incidence of Optimizer device- or procedure-related complications within the first 12 months after implant

  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.

  12 months

• Part 2 Endpoint - The hierarchical composite of mortality, morbidity, and health status outcomes (KCCQ CSS).

  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.

  18 months

Study Arms (2)

CCM Group (CCM ON)

EXPERIMENTAL

CCM therapy will be turned on in 2/3 of the subjects for the entire duration of the study.

Device: Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System

Sham Group (CCM OFF)

SHAM COMPARATOR

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.

Device: OPTIMIZER™ Smart Mini System

Interventions

OPTIMIZER™ Smart Mini System DEVICE

The OPTIMIZER™ Smart Mini System will be implanted and CCM will be programmed OFF for the first 18 months (blinded phase). CCM will be turned on following completion of the 18-month visit.

Also known as: Sham Group (CCM OFF)

Sham Group (CCM OFF)

Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System DEVICE

The OPTIMIZER™ Smart Mini System will be implanted and CCM will be programmed ON for the first 18 months (blinded phase). CCM therapy will be programmed to deliver 7 one-hour phases of CCM therapy that are distributed equally over every 24-hour period. CCM will remain on following completion of the 18-month visit.

Also known as: CCM Group (CCM ON)

CCM Group (CCM ON)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent form;
• Male or non-pregnant female, 18 years or older;
• Diagnosed with symptomatic heart failure;
• LVEF ≥40 and ≤70% (as assessed by site echo);
• 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)
• 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.

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• Impulse Dynamics: lead

Study Sites (105)

Grandview Medical Group Research, LLC

Birmingham, Alabama, 35243, United States

RECRUITING

CardioVascular Associates of Mesa

Mesa, Arizona, 85206, United States

RECRUITING

Chan Heart Rhythm Institute

Mesa, Arizona, 85206, United States

RECRUITING

Southwest Cardiovascular Associates

Mesa, Arizona, 85208, United States

RECRUITING

Arizona Heart Rhythm

Phoenix, Arizona, 85016, United States

RECRUITING

Cardiovascular Consultants, Ltd

Phoenix, Arizona, 85032, United States

RECRUITING

HonorHealth

Scottsdale, Arizona, 85258, United States

RECRUITING

Pima Heart and Vascular

Tuscon, Arizona, 85712, United States

RECRUITING

John Muir Health

Concord, California, 94520, United States

RECRUITING

University of California San Diego

La Jolla, California, 92093, United States

RECRUITING

USC Keck School of Medicine

Los Angeles, California, 90033, United States

RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Valley Clinical Trials- Northridge

Northridge, California, 91325, United States

RECRUITING

Sequoia Hospital

Redwood City, California, 94062, United States

RECRUITING

University of California Davis Health

Sacramento, California, 95817, United States

WITHDRAWN

University of California, San Francisco

San Francisco, California, 94143, United States

WITHDRAWN

Nuvance Health - Danbury Hospital

Danbury, Connecticut, 06810, United States

RECRUITING

Hartford Healthcare

Hartford, Connecticut, 06103, United States

RECRUITING

HCA Florida JFK Hospital

Atlantis, Florida, 33462, United States

RECRUITING

Nouvelle Clinical Research LLC

Cutler Bay, Florida, 33189, United States

RECRUITING

Broward Health

Fort Lauderdale, Florida, 33316, United States

RECRUITING

Memorial Healthcare System

Hollywood, Florida, 33021, United States

WITHDRAWN

Baptist Health South Florida

Miami, Florida, 33176, United States

RECRUITING

NCA Research Institute - Florida

Naples, Florida, 34102, United States

WITHDRAWN

AdventHealth Orlando

Orlando, Florida, 32803, United States

RECRUITING

Revival Clinical Research

Orlando, Florida, 32807, United States

RECRUITING

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

WITHDRAWN

Cleveland Clinic Foundation - Florida Weston Hospital

Weston, Florida, 33326, United States

RECRUITING

Piedmont Healthcare

Atlanta, Georgia, 30309, United States

WITHDRAWN

Franciscan Health Indianapolis

Indianapolis, Indiana, 46237, United States

WITHDRAWN

Ascension Medical Group St. Vincent

Indianapolis, Indiana, 46260, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

MercyOne Iowa Heart

West Des Moines, Iowa, 50266, United States

RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

Kansas City Cardiac Arrhythmia Research LLC

Overland Park, Kansas, 66211, United States

RECRUITING

Baptist Health Lexington

Lexington, Kentucky, 40503, United States

RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

WITHDRAWN

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

University of Michigan

Ann Arbor, Michigan, 48113, United States

RECRUITING

Henry Ford St. John Hospital

Detroit, Michigan, 48236, United States

RECRUITING

Ascension Providence Hospital

Southfield, Michigan, 48075, United States

RECRUITING

Trinity health- Michigan Heart

Ypsilanti, Michigan, 48197, United States

RECRUITING

Minneapolis Heart Institute at Abbott Northwestern Hospital

Minneapolis, Minnesota, 55407, United States

RECRUITING

North Mississippi Medical Center

Tupelo, Mississippi, 38801, United States

WITHDRAWN

St. Louis Heart and Vascular

Bridgeton, Missouri, 63044, United States

RECRUITING

St. Luke&#39;s Hospital

Chesterfield, Missouri, 63017, United States

WITHDRAWN

St. Lukes Hospital Kansas City (Mid America Heart Institute)

Kansas City, Missouri, 64111, United States

RECRUITING

Bryan Heart

Lincoln, Nebraska, 68506, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198-5331, United States

WITHDRAWN

Catholic Medical Center

Manchester, New Hampshire, 03102, United States

WITHDRAWN

Our Lady of Lourdes

Camden, New Jersey, 08103, United States

RECRUITING

Hackensack University Medical Center

Edison, New Jersey, 08837, United States

WITHDRAWN

Jersey Shore University Medical Center

Edison, New Jersey, 08837, United States

WITHDRAWN

Cooper Hospital- Cardiovascular Associates of Delaware Valley

Haddon Heights, New Jersey, 08035, United States

RECRUITING

Atlantic Health System- Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

Rutgers New Jersey Medical School

Piscataway, New Jersey, 08854, United States

WITHDRAWN

AtlantiCare Regional Medical Center

Pomona, New Jersey, 08240, United States

RECRUITING

Buffalo General

Buffalo, New York, 14203, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10021, United States

WITHDRAWN

Nuvance Health - Heart & Vascular Institute/Hudson Valley Cardiovascular Practice, PC

Poughkeepsie, New York, 12601, United States

RECRUITING

Nuvance Health - Vassar brothers Medical Center

Poughkeepsie, New York, 12601, United States

RECRUITING

Sanger Heart and Vascular

Charlotte, North Carolina, 28203, United States

WITHDRAWN

TriHealth Bethesda

Cincinnati, Ohio, 45202, United States

WITHDRAWN

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

WITHDRAWN

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

RECRUITING

Mercy Health- St. Vincent Medical Center LLC

Toledo, Ohio, 43608, United States

WITHDRAWN

Oklahoma Heart Institute

Tulsa, Oklahoma, 74104, United States

RECRUITING

St. Francis Hospital - Tulsa

Tulsa, Oklahoma, 74136, United States

RECRUITING

Providence Heart & Vascular

Portland, Oregon, 97225, United States

RECRUITING

Bryn Mawr Medical Specialists Association

Bryn Mawr, Pennsylvania, 19010, United States

RECRUITING

UPMC Pinnacle Harrisburg

Harrisburg, Pennsylvania, 17110, United States

WITHDRAWN

Penn State Hershey Medical City

Hershey, Pennsylvania, 17033, United States

RECRUITING

Lancaster General Hospital

Lancaster, Pennsylvania, 17602, United States

WITHDRAWN

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, 19104-6061, United States

RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Tower Health Reading Hospital

Reading, Pennsylvania, 19611, United States

WITHDRAWN

WellSpan Health

York, Pennsylvania, 17403, United States

WITHDRAWN

Prisma Health Upstate

Greenville, South Carolina, 29601, United States

RECRUITING

Bon Secours Upstate Cardiology

Greenville, South Carolina, 29607, United States

WITHDRAWN

North Central Heart

Sioux Falls, South Dakota, 57108, United States

RECRUITING

The Stern Cardiovascular Foundation

Germantown, Tennessee, 38138, United States

RECRUITING

Texas Cardiac Arrhythmia Research Foundation

Austin, Texas, 78705, United States

WITHDRAWN

Ascension Seton

Austin, Texas, 78723, United States

RECRUITING

Austin Heart

Austin, Texas, 78756, United States

RECRUITING

Baylor Scott and White Research Institute

Dallas, Texas, 75204, United States

RECRUITING

HCA Medical City Dallas

Dallas, Texas, 75230, United States

WITHDRAWN

Baylor Scott White- All Saints- Fort Worth

Fort Worth, Texas, 76104, United States

RECRUITING

Medical City Fort Worth Hospital

Fort Worth, Texas, 76104, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Houston Methodist

Houston, Texas, 77030, United States

RECRUITING

Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States

RECRUITING

Heart Rhythm Specialists

McKinney, Texas, 75070, United States

RECRUITING

Baylor Scott and White- The Heart Hospital- Plano

Plano, Texas, 75093, United States

WITHDRAWN

Baylor Scott and White Research Institute - Round Rock

Round Rock, Texas, 78665, United States

RECRUITING

Methodist Hospital

San Antonio, Texas, 78229, United States

WITHDRAWN

Bon Secours St. Mary's

Richmond, Virginia, 23114, United States

RECRUITING

Bon Secours St. Mary's

Richmond, Virginia, 23226, United States

RECRUITING

Swedish Medical Center

Seattle, Washington, 98122, United States

RECRUITING

Peace Health

Vancouver, Washington, 98664, United States

RECRUITING

Related Publications (4)

• Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.

  PMID: 29754812 BACKGROUND

• Wiegn P, Chan R, Jost C, Saville BR, Parise H, Prutchi D, Carson PE, Stagg A, Goldsmith RL, Burkhoff D. Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System: The FIX-HF-5C2 Study. Circ Heart Fail. 2020 Apr;13(4):e006512. doi: 10.1161/CIRCHEARTFAILURE.119.006512. Epub 2020 Apr 8.

  PMID: 32264716 BACKGROUND

• Tschope C, Butler J, Farmakis D, Morley D, Rao I, Filippatos G. Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function. ESC Heart Fail. 2020 Dec;7(6):3531-3535. doi: 10.1002/ehf2.13126. Epub 2020 Dec 3.

  PMID: 33274601 BACKGROUND

• Tschope C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, Gutterman D, Linke WA, Pieske B, Hamdani N, Roser M. Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF. Int J Cardiol. 2016 Jan 15;203:1061-6. doi: 10.1016/j.ijcard.2015.10.208. Epub 2015 Oct 27. No abstract available.

  PMID: 26638055 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Heart Failure, Diastolic

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Javed Butler, MD, MPH, MBA

  Baylor Scott and White Research Institute, Dallas, Texas

  PRINCIPAL INVESTIGATOR

• Oussama Wazni, MD, MBA

  Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rachael Riccitello

CONTACT

856-434-7981; aimhigher@impulsedynamics.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In addition to the subject, the entire site research team, the implanting physician, the Clinical Events Committee (CEC), and the clinical study monitors will all be blinded to the treatment assignment. Site research staff and Impulse Dynamics monitoring personnel will not have viewing rights to the randomization assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, multi-national, randomized, quadruple-blind, sham controlled, 2-part, embedded IDE clinical trial

Study Record Dates

• First Submitted: September 21, 2021
• First Posted: October 1, 2021
• Study Start: February 3, 2022
• Primary Completion (Estimated): February 1, 2029
• Study Completion (Estimated): February 1, 2029
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (105)