Assessment of CCM in HF With Higher Ejection Fraction (AIM HIGHer)

May 4, 2026 updated by: Impulse Dynamics

Assessment of Implantable CCM in the Heart Failure Group With Higher Ejection Fraction

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%.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

1500

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35243
    • Arizona
      • Mesa, Arizona, United States, 85206
      • Mesa, Arizona, United States, 85206
        • Recruiting
        • CardioVascular Associates of Mesa
        • Contact:
      • Mesa, Arizona, United States, 85208
        • Recruiting
        • Southwest Cardiovascular Associates
        • Contact:
      • Phoenix, Arizona, United States, 85016
      • Phoenix, Arizona, United States, 85032
      • Scottsdale, Arizona, United States, 85258
      • Tuscon, Arizona, United States, 85712
    • California
      • Concord, California, United States, 94520
      • La Jolla, California, United States, 92093
      • Los Angeles, California, United States, 90048
      • Los Angeles, California, United States, 90033
      • Northridge, California, United States, 91325
      • Redwood City, California, United States, 94062
      • Sacramento, California, United States, 95817
        • Withdrawn
        • University of California Davis Health
      • San Francisco, California, United States, 94143
        • Withdrawn
        • University of California, San Francisco
    • Connecticut
    • Florida
      • Atlantis, Florida, United States, 33462
      • Cutler Bay, Florida, United States, 33189
      • Fort Lauderdale, Florida, United States, 33316
      • Hollywood, Florida, United States, 33021
        • Withdrawn
        • Memorial Healthcare System
      • Miami, Florida, United States, 33176
      • Naples, Florida, United States, 34102
        • Withdrawn
        • NCA Research Institute - Florida
      • Orlando, Florida, United States, 32803
      • Orlando, Florida, United States, 32807
      • Tallahassee, Florida, United States, 32308
        • Withdrawn
        • Tallahassee Research Institute
      • Weston, Florida, United States, 33326
        • Recruiting
        • Cleveland Clinic Foundation - Florida Weston Hospital
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 30309
        • Withdrawn
        • Piedmont Healthcare
    • Indiana
      • Indianapolis, Indiana, United States, 46260
      • Indianapolis, Indiana, United States, 46237
        • Withdrawn
        • Franciscan Health Indianapolis
    • Iowa
    • Kansas
    • Kentucky
      • Lexington, Kentucky, United States, 40503
        • Recruiting
        • Baptist Health Lexington
        • Contact:
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Withdrawn
        • Ochsner Clinic Foundation
    • Massachusetts
    • Michigan
      • Ann Arbor, Michigan, United States, 48113
        • Recruiting
        • University of Michigan
        • Contact:
        • Principal Investigator:
          • Thomas Crawford, MD
      • Detroit, Michigan, United States, 48236
      • Southfield, Michigan, United States, 48075
      • Ypsilanti, Michigan, United States, 48197
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Recruiting
        • Minneapolis Heart Institute at Abbott Northwestern Hospital
        • Contact:
    • Mississippi
      • Tupelo, Mississippi, United States, 38801
        • Withdrawn
        • North Mississippi Medical Center
    • Missouri
      • Bridgeton, Missouri, United States, 63044
        • Recruiting
        • St. Louis Heart and Vascular
        • Contact:
      • Chesterfield, Missouri, United States, 63017
        • Withdrawn
        • St. Luke's Hospital
      • Kansas City, Missouri, United States, 64111
        • Recruiting
        • St. Lukes Hospital Kansas City (Mid America Heart Institute)
        • Contact:
    • Nebraska
      • Lincoln, Nebraska, United States, 68506
      • Omaha, Nebraska, United States, 68198-5331
        • Withdrawn
        • University of Nebraska Medical Center
    • New Hampshire
      • Manchester, New Hampshire, United States, 03102
        • Withdrawn
        • Catholic Medical Center
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Recruiting
        • Our Lady of Lourdes
        • Contact:
      • Edison, New Jersey, United States, 08837
        • Withdrawn
        • Hackensack University Medical Center
      • Edison, New Jersey, United States, 08837
        • Withdrawn
        • Jersey Shore University Medical Center
      • Haddon Heights, New Jersey, United States, 08035
        • Recruiting
        • Cooper Hospital- Cardiovascular Associates of Delaware Valley
        • Contact:
      • Morristown, New Jersey, United States, 07960
      • Piscataway, New Jersey, United States, 08854
        • Withdrawn
        • Rutgers New Jersey Medical School
      • Pomona, New Jersey, United States, 08240
        • Recruiting
        • AtlantiCare Regional Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Haitham Dib, MD
    • New York
      • Buffalo, New York, United States, 14203
        • Recruiting
        • Buffalo General
        • Contact:
        • Principal Investigator:
          • Robert Cimato, MD, PhD
      • New York, New York, United States, 10021
        • Withdrawn
        • Weill Cornell Medicine
      • Poughkeepsie, New York, United States, 12601
        • Recruiting
        • Nuvance Health - Heart & Vascular Institute/Hudson Valley Cardiovascular Practice, PC
        • Contact:
      • Poughkeepsie, New York, United States, 12601
    • North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Withdrawn
        • Sanger Heart and Vascular
    • Ohio
      • Cincinnati, Ohio, United States, 45202
        • Withdrawn
        • TriHealth Bethesda
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic Foundation
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Withdrawn
        • University Hospitals Cleveland Medical Center
      • Columbus, Ohio, United States, 43214
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Wexner Medical Center
        • Contact:
      • Toledo, Ohio, United States, 43608
        • Withdrawn
        • Mercy Health- St. Vincent Medical Center LLC
    • Oklahoma
    • Oregon
    • Pennsylvania
      • Bryn Mawr, Pennsylvania, United States, 19010
        • Recruiting
        • Bryn Mawr Medical Specialists Association
        • Contact:
      • Harrisburg, Pennsylvania, United States, 17110
        • Withdrawn
        • UPMC Pinnacle Harrisburg
      • Hershey, Pennsylvania, United States, 17033
      • Lancaster, Pennsylvania, United States, 17602
        • Withdrawn
        • Lancaster General Hospital
      • Philadelphia, Pennsylvania, United States, 19107
        • Recruiting
        • Thomas Jefferson University Hospital
        • Contact:
        • Principal Investigator:
          • Susan Joseph, MD
      • Philadelphia, Pennsylvania, United States, 19140
      • Philadelphia, Pennsylvania, United States, 19104
      • Philadelphia, Pennsylvania, United States, 19104-6061
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh Medical Center
        • Contact:
      • Pittsburgh, Pennsylvania, United States, 15212
      • Reading, Pennsylvania, United States, 19611
        • Withdrawn
        • Tower Health Reading Hospital
      • York, Pennsylvania, United States, 17403
        • Withdrawn
        • WellSpan Health
    • South Carolina
      • Greenville, South Carolina, United States, 29601
      • Greenville, South Carolina, United States, 29607
        • Withdrawn
        • Bon Secours Upstate Cardiology
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57108
        • Recruiting
        • North Central Heart
        • Contact:
        • Principal Investigator:
          • Ovar Jonsson, MD, FACC
    • Tennessee
    • Texas
      • Austin, Texas, United States, 78756
      • Austin, Texas, United States, 78723
      • Austin, Texas, United States, 78705
        • Withdrawn
        • Texas Cardiac Arrhythmia Research Foundation
      • Dallas, Texas, United States, 75204
        • Recruiting
        • Baylor Scott and White Research Institute
        • Contact:
      • Dallas, Texas, United States, 75230
        • Withdrawn
        • HCA Medical City Dallas
      • Fort Worth, Texas, United States, 76104
      • Fort Worth, Texas, United States, 76104
      • Houston, Texas, United States, 77030
        • Recruiting
        • Baylor College of Medicine
        • Contact:
      • Houston, Texas, United States, 77030
      • Houston, Texas, United States, 77030
      • McKinney, Texas, United States, 75070
      • Plano, Texas, United States, 75093
        • Withdrawn
        • Baylor Scott and White- The Heart Hospital- Plano
      • Round Rock, Texas, United States, 78665
      • San Antonio, Texas, United States, 78229
        • Withdrawn
        • Methodist Hospital
    • Virginia
      • Richmond, Virginia, United States, 23226
        • Recruiting
        • Bon Secours St. Mary's
        • Contact:
        • Principal Investigator:
          • LaVone Smith, MD
      • Richmond, Virginia, United States, 23114
        • Recruiting
        • Bon Secours St. Mary's
        • Contact:
        • Principal Investigator:
          • LaVonne Smith, MD
    • Washington
      • Seattle, Washington, United States, 98122
      • Vancouver, Washington, United States, 98664

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CCM Group (CCM ON)
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
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.
Other Names:
  • CCM Group (CCM ON)
Sham Comparator: 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.
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.
Other Names:
  • Sham Group (CCM OFF)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Time Frame: 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.
6 months
Part 1 Safety Endpoint - The incidence of Optimizer device- or procedure-related complications within the first 12 months after implant
Time Frame: 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.
12 months
Part 2 Endpoint - The hierarchical composite of mortality, morbidity, and health status outcomes (KCCQ CSS).
Time Frame: 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.
18 months
Part 1 Efficacy Endpoint - Change in 6-minute walk distance (6MWD) from baseline to 6 months.
Time Frame: 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Impulse Dynamics

Investigators

  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 3, 2022

Primary Completion (Estimated)

February 1, 2029

Study Completion (Estimated)

February 1, 2029

Study Registration Dates

First Submitted

September 21, 2021

First Submitted That Met QC Criteria

September 30, 2021

First Posted (Actual)

October 1, 2021

Study Record Updates

Last Update Posted (Actual)

May 6, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA_CP_340

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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