Assessment of CCM in HF With Higher Ejection Fraction

NCT ID: NCT05064709

Last Updated: 2026-01-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

1500 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-03

Study Completion Date

2029-02-01

Brief Summary

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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

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicenter, multi-national, randomized, quadruple-blind, sham controlled, 2-part, embedded IDE clinical trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
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.

Study Groups

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CCM Group (CCM ON)

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

Group Type EXPERIMENTAL

Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System

Intervention Type 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.

Sham Group (CCM OFF)

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.

Group Type SHAM_COMPARATOR

OPTIMIZER™ Smart Mini System

Intervention Type 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.

Interventions

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Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System

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.

Intervention Type DEVICE

OPTIMIZER™ Smart Mini System

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.

Intervention Type DEVICE

Other Intervention Names

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CCM Group (CCM ON) Sham Group (CCM OFF)

Eligibility Criteria

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Inclusion Criteria

1. Signed and dated informed consent form;
2. Male or non-pregnant female, 18 years or older;
3. Diagnosed with symptomatic heart failure;
4. LVEF ≥40 and ≤70% (as assessed by site echo);
5. 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)
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.
* 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.

Exclusion Criteria

1. Resting ventricular rate \<50 or \>110 bpm;
2. Resting systolic blood pressure \<100 or ≥160 mmHg;
3. BMI greater than 46
4. Any severe valvular stenotic disease or any severe valvular regurgitation;
5. Mechanical tricuspid valve;
6. Complex congenital heart disease;
7. 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;
8. Unable to walk at least 100 meters or walks more than 450 meters during a 6MWT;
9. A KCCQ CCS score higher than 85;
10. Hypertrophic, infiltrative/restrictive or inflammatory cardiomyopathy;
11. Unstable angina pectoris within 30 days prior to study consent;
12. Acute, decompensated heart failure requiring IV therapy or ultrafiltration within 30 days prior to consent, in the hospital or an outpatient setting;
13. 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.
14. 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;
15. Myocardial infarction within 90 days prior to study consent;
16. Prior heart transplant or ventricular assist device;
17. Planning to become pregnant during the study;
18. Dialysis (permanent) or GFR \<15 ml/min/1.73m2;
19. Participating in another investigational drug or device study that may interfere with the interpretation of study data;
20. 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;
21. Expected lifespan of less than 18 months from time of study consent;
22. Unable to follow through study protocol for any reasons in the investigator's judgement.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Impulse Dynamics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Javed Butler, MD, MPH, MBA

Role: PRINCIPAL_INVESTIGATOR

Baylor Scott and White Research Institute, Dallas, Texas

Oussama Wazni, MD, MBA

Role: PRINCIPAL_INVESTIGATOR

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

Locations

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Grandview Medical Group Research, LLC

Birmingham, Alabama, United States

Site Status RECRUITING

The University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status WITHDRAWN

CardioVascular Associates of Mesa

Mesa, Arizona, United States

Site Status RECRUITING

Chan Heart Rhythm Institute

Mesa, Arizona, United States

Site Status RECRUITING

Southwest Cardiovascular Associates

Mesa, Arizona, United States

Site Status RECRUITING

Banner Health- Phoenix

Phoenix, Arizona, United States

Site Status WITHDRAWN

Arizona Heart Rhythm

Phoenix, Arizona, United States

Site Status RECRUITING

Cardiovascular Consultants, Ltd

Phoenix, Arizona, United States

Site Status RECRUITING

HonorHealth

Scottsdale, Arizona, United States

Site Status RECRUITING

Pima Heart and Vascular

Tuscon, Arizona, United States

Site Status RECRUITING

John Muir Health

Concord, California, United States

Site Status RECRUITING

Northbay Heart and Vascular

Fairfield, California, United States

Site Status WITHDRAWN

University of California San Diego

La Jolla, California, United States

Site Status RECRUITING

USC Keck School of Medicine

Los Angeles, California, United States

Site Status RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Valley Clinical Trials Pasadena

Northridge, California, United States

Site Status WITHDRAWN

Valley Clinical Trials- Northridge

Northridge, California, United States

Site Status RECRUITING

Sequoia Hospital

Redwood City, California, United States

Site Status RECRUITING

University of California Davis Health

Sacramento, California, United States

Site Status WITHDRAWN

University of California, San Francisco

San Francisco, California, United States

Site Status WITHDRAWN

Nuvance Health - Danbury Hospital

Danbury, Connecticut, United States

Site Status RECRUITING

Hartford Healthcare

Hartford, Connecticut, United States

Site Status RECRUITING

HCA Florida JFK Hospital

Atlantis, Florida, United States

Site Status RECRUITING

Nouvelle Clinical Research LLC

Cutler Bay, Florida, United States

Site Status RECRUITING

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status WITHDRAWN

Broward Health

Fort Lauderdale, Florida, United States

Site Status RECRUITING

Memorial Healthcare System

Hollywood, Florida, United States

Site Status WITHDRAWN

Baptist Health South Florida

Miami, Florida, United States

Site Status RECRUITING

NCA Research Institute - Florida

Naples, Florida, United States

Site Status WITHDRAWN

AdventHealth Orlando

Orlando, Florida, United States

Site Status RECRUITING

Revival Clinical Research

Orlando, Florida, United States

Site Status RECRUITING

Tallahassee Research Institute

Tallahassee, Florida, United States

Site Status WITHDRAWN

Cleveland Clinic Foundation - Florida Weston Hospital

Weston, Florida, United States

Site Status RECRUITING

Piedmont Healthcare

Atlanta, Georgia, United States

Site Status WITHDRAWN

WellStar Health System, Inc

Marietta, Georgia, United States

Site Status RECRUITING

Franciscan Health Indianapolis

Indianapolis, Indiana, United States

Site Status WITHDRAWN

Ascension Medical Group St. Vincent

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

MercyOne Iowa Heart

West Des Moines, Iowa, United States

Site Status RECRUITING

University of Kansas Medical Center

Kansas City, Kansas, United States

Site Status RECRUITING

Kansas City Cardiac Arrhythmia Research LLC

Overland Park, Kansas, United States

Site Status RECRUITING

Baptist Health Lexington

Lexington, Kentucky, United States

Site Status RECRUITING

University of Kentucky Research Foundation

Lexington, Kentucky, United States

Site Status RECRUITING

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status WITHDRAWN

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Henry Ford St. John Hospital

Detroit, Michigan, United States

Site Status RECRUITING

Ascension Providence Hospital

Southfield, Michigan, United States

Site Status RECRUITING

Trinity health- Michigan Heart

Ypsilanti, Michigan, United States

Site Status RECRUITING

Minneapolis Heart Institute at Abbott Northwestern Hospital

Minneapolis, Minnesota, United States

Site Status RECRUITING

North Mississippi Medical Center

Tupelo, Mississippi, United States

Site Status WITHDRAWN

St. Louis Heart and Vascular

Bridgeton, Missouri, United States

Site Status RECRUITING

St. Luke&#39;s Hospital

Chesterfield, Missouri, United States

Site Status WITHDRAWN

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

Kansas City, Missouri, United States

Site Status RECRUITING

Bryan Heart

Lincoln, Nebraska, United States

Site Status RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status WITHDRAWN

Catholic Medical Center

Manchester, New Hampshire, United States

Site Status WITHDRAWN

Our Lady of Lourdes

Camden, New Jersey, United States

Site Status RECRUITING

Hackensack University Medical Center

Edison, New Jersey, United States

Site Status WITHDRAWN

Jersey Shore University Medical Center

Edison, New Jersey, United States

Site Status WITHDRAWN

Cooper Hospital- Cardiovascular Associates of Delaware Valley

Haddon Heights, New Jersey, United States

Site Status RECRUITING

Atlantic Health System- Morristown Medical Center

Morristown, New Jersey, United States

Site Status RECRUITING

Rutgers New Jersey Medical School

Piscataway, New Jersey, United States

Site Status WITHDRAWN

AtlantiCare Regional Medical Center

Pomona, New Jersey, United States

Site Status RECRUITING

Buffalo General

Buffalo, New York, United States

Site Status RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status WITHDRAWN

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

Poughkeepsie, New York, United States

Site Status RECRUITING

Nuvance Health - Vassar brothers Medical Center

Poughkeepsie, New York, United States

Site Status RECRUITING

Sanger Heart and Vascular

Charlotte, North Carolina, United States

Site Status WITHDRAWN

TriHealth Bethesda

Cincinnati, Ohio, United States

Site Status WITHDRAWN

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status WITHDRAWN

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

OhioHealth Research Institute

Columbus, Ohio, United States

Site Status RECRUITING

Mercy Health- St. Vincent Medical Center LLC

Toledo, Ohio, United States

Site Status WITHDRAWN

Oklahoma Heart Institute

Tulsa, Oklahoma, United States

Site Status RECRUITING

St. Francis Hospital - Tulsa

Tulsa, Oklahoma, United States

Site Status RECRUITING

Providence Heart & Vascular

Portland, Oregon, United States

Site Status RECRUITING

Bryn Mawr Medical Specialists Association

Bryn Mawr, Pennsylvania, United States

Site Status RECRUITING

UPMC Pinnacle Harrisburg

Harrisburg, Pennsylvania, United States

Site Status WITHDRAWN

Penn State Hershey Medical City

Hershey, Pennsylvania, United States

Site Status RECRUITING

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Site Status WITHDRAWN

Penn Presbyterian Medical Center

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Tower Health Reading Hospital

Reading, Pennsylvania, United States

Site Status WITHDRAWN

WellSpan Health

York, Pennsylvania, United States

Site Status WITHDRAWN

Prisma Health Upstate

Greenville, South Carolina, United States

Site Status RECRUITING

Bon Secours Upstate Cardiology

Greenville, South Carolina, United States

Site Status WITHDRAWN

North Central Heart

Sioux Falls, South Dakota, United States

Site Status RECRUITING

The Stern Cardiovascular Foundation

Germantown, Tennessee, United States

Site Status RECRUITING

Texas Cardiac Arrhythmia Research Foundation

Austin, Texas, United States

Site Status WITHDRAWN

Ascension Seton

Austin, Texas, United States

Site Status RECRUITING

Austin Heart

Austin, Texas, United States

Site Status RECRUITING

Baylor Scott and White Research Institute

Dallas, Texas, United States

Site Status RECRUITING

HCA Medical City Dallas

Dallas, Texas, United States

Site Status WITHDRAWN

Baylor Scott White- All Saints- Fort Worth

Fort Worth, Texas, United States

Site Status RECRUITING

Medical City Fort Worth Hospital

Fort Worth, Texas, United States

Site Status RECRUITING

Baylor College of Medicine

Houston, Texas, United States

Site Status RECRUITING

Houston Methodist

Houston, Texas, United States

Site Status RECRUITING

Memorial Hermann Texas Medical Center

Houston, Texas, United States

Site Status RECRUITING

Heart Rhythm Specialists

McKinney, Texas, United States

Site Status RECRUITING

Baylor Scott and White- The Heart Hospital- Plano

Plano, Texas, United States

Site Status WITHDRAWN

Baylor Scott and White Research Institute - Round Rock

Round Rock, Texas, United States

Site Status RECRUITING

Methodist Hospital

San Antonio, Texas, United States

Site Status WITHDRAWN

Bon Secours St. Mary's

Richmond, Virginia, United States

Site Status RECRUITING

Bon Secours St. Mary's

Richmond, Virginia, United States

Site Status RECRUITING

Swedish Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Peace Health

Vancouver, Washington, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rachael Riccitello

Role: CONTACT

856-434-7981

Facility Contacts

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Lauren Bryant

Role: primary

2059717553

Adam Gitkin

Role: primary

4806415400 ext. 2107

Olivia Rivera

Role: primary

Kim Helgeson

Role: primary

4809454343 ext. 244

Brandon Buscaglia

Role: primary

Helen Foughi

Role: primary

Rachel Hultman

Role: primary

Monica Varela

Role: primary

5203294139

Rita Trachuk

Role: primary

Kendell Oliver

Role: primary

Melissa Ramos

Role: primary

Silvia Perez

Role: backup

Goran Stankovic

Role: primary

Haydee Gutierrez

Role: primary

Juanita Fujii

Role: primary

Tricia Landi

Role: primary

Jennifer Rossi

Role: primary

Elizabeth Diebel

Role: primary

Alexander Cabrera

Role: primary

Nilda Cespedes

Role: backup

Laura Hudson

Role: primary

Jetsenea Coto

Role: primary

7865962421

Chanti Garvey

Role: primary

Joseniesse Figueroa

Role: primary

Maria Mejia Gomez

Role: primary

Jessica Drury

Role: primary

Denise Grove

Role: backup

Sabrina Rotondo

Role: primary

Trisha Elliott

Role: primary

Cayla Garner

Role: primary

Quratulain (Annie) Mushtaq

Role: primary

9139456488

Donita Atkins

Role: primary

Jenny Bush

Role: backup

Kristie Schneider

Role: primary

8592606429

Ronald Smith

Role: primary

Chinemerem Nwokemodo-Ihejirika

Role: primary

Kirsta Bray

Role: primary

Renee Bess

Role: primary

Candice Edillo

Role: primary

Autumn Howe

Role: primary

Jessica Whelan

Role: primary

6128631661

Paige Brown

Role: primary

3147410911 ext. 4044

Amanda Huffman

Role: primary

Nicci Thompson

Role: primary

Marisa Brown

Role: primary

8563551226

Erin Siderio

Role: primary

8565822000 ext. 5207

Diane Agar

Role: primary

9739714205

Jackie White

Role: primary

609-652-3550

Alison Hallam

Role: backup

609-652-3550

Courtney Bishop

Role: primary

716-888-4859

Tricia Landi

Role: primary

845-473-8675

Tricia Landi

Role: primary

845-473-8675

Barbara Gus

Role: primary

Maeve McLoughlin

Role: primary

6142924084

Reem (Mimi) Bekheet

Role: primary

Colene Holland son

Role: primary

Miriam Brooks

Role: backup

Martha Dixon

Role: primary

918-671-8660

Sarah Jackson

Role: primary

Morgan Battiste

Role: primary

Lisa Fox

Role: primary

Katie Shoemaker

Role: primary

Emily Marvel

Role: primary

Blaire Cain

Role: primary

484-756-0929

Kriti Rawat

Role: primary

Kelly Kuniak

Role: primary

Traci McGaha

Role: primary

Kenneth Alfieri

Role: primary

8644557793

Robin Farley

Role: primary

Kristen Page

Role: primary

Kari Fondren

Role: backup

Sarah Benedict

Role: primary

Mary Fraser

Role: primary

Tein Luu

Role: primary

2148651685 ext. 481685

Felicity Vaughan

Role: primary

8179222575

Jessica Blades

Role: primary

Brenda Tapia

Role: backup

Stephen Harold

Role: primary

Deborah Barr

Role: primary

Lawana Self

Role: primary

Isabella Lefebvre

Role: backup

Emily Buchanan

Role: primary

Catherine Lyman

Role: primary

Janet Barrett

Role: primary

804-794-6400|

Janet Barrett

Role: primary

804-794-6400

Michelle Garcia

Role: primary

Nancy Fitch

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 29754812 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32264716 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33274601 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26638055 (View on PubMed)

Other Identifiers

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CA_CP_340

Identifier Type: -

Identifier Source: org_study_id

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