Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05064709
Other study ID # CA_CP_340
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date February 3, 2022
Est. completion date February 1, 2026

Study information

Verified date September 2023
Source Impulse Dynamics
Contact Maria Fernanda Villarreal, MD
Phone 8453592389
Email aimhigher@impulsedynamics.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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 ≤60%.


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 ≤60%. 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 information / eligibility

Status Recruiting
Enrollment 1500
Est. completion date February 1, 2026
Est. primary completion date February 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 =60% (as assessed by echo core lab); 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, AND elevated BMI-adjusted natriuretic peptide values (Refer to Table A in Section 9.2.6) 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 B in Section 9.2.6) 6. Subjects must be on stable, scheduled oral loop diuretic treatment (not only PRN) for at least 30 days prior to study consent, unless documented allergy/intolerance. 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); 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 <20 ml/min/1.73m2; 19. Participating in another investigational study; 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;

Study Design


Related Conditions & MeSH terms


Intervention

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.
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.

Locations

Country Name City State
United States Piedmont Healthcare Atlanta Georgia
United States HCA Florida JFK Hospital Atlantis Florida
United States Ascension Seton Austin Texas
United States Austin Heart Austin Texas
United States Texas Cardiac Arrhythmia Research Foundation Austin Texas
United States Grandview Medical Group Research, LLC Birmingham Alabama
United States The University of Alabama at Birmingham Birmingham Alabama
United States Massachusetts General Hospital Boston Massachusetts
United States St. Louis Heart and Vascular Bridgeton Missouri
United States Bryn Mawr Medical Specialists Association Bryn Mawr Pennsylvania
United States Our Lady of Lourdes Camden New Jersey
United States Sanger Heart and Vascular Charlotte North Carolina
United States St. Luke's Hospital Chesterfield Missouri
United States TriHealth Bethesda Cincinnati Ohio
United States Cleveland Clinic Foundation Cleveland Ohio
United States University Hospitals Cleveland Medical Center Cleveland Ohio
United States Ohio State University Wexner Medical Center Columbus Ohio
United States OhioHealth Research Institute Columbus Ohio
United States John Muir Health Concord California
United States Nouvelle Clinical Research LLC Cutler Bay Florida
United States Baylor Scott and White Research Institute Dallas Texas
United States HCA Medical City Dallas Dallas Texas
United States Ascension St. John Detroit Michigan
United States Hackensack University Medical Center Edison New Jersey
United States Jersey Shore University Medical Center Edison New Jersey
United States Northbay Heart and Vascular Fairfield California
United States Broward Health Fort Lauderdale Florida
United States Holy Cross Hospital Fort Lauderdale Florida
United States Baylor Scott White- All Saints- Fort Worth Fort Worth Texas
United States Medical City Fort Worth Hospital Fort Worth Texas
United States The Stern Cardiovascular Foundation Germantown Tennessee
United States Prisma Health Upstate Greenville South Carolina
United States Cooper Hospital- Cardiovascular Associates of Delaware Valley Haddon Heights New Jersey
United States UPMC Pinnacle Harrisburg Harrisburg Pennsylvania
United States Hartford Healthcare Hartford Connecticut
United States Penn State Hershey Medical City Hershey Pennsylvania
United States Memorial Healthcare System Hollywood Florida
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 Ascension Medical Group St. Vincent Indianapolis Indiana
United States Franciscan Health Indianapolis Indianapolis Indiana
United States University of Iowa Iowa City Iowa
United States St. Lukes Hospital Kansas City (Mid America Heart Institute) Kansas City Missouri
United States University of Kansas Medical Center Kansas City Kansas
United States University of California San Diego La Jolla California
United States Lancaster General Hospital Lancaster Pennsylvania
United States Baptist Health Lexington Lexington Kentucky
United States University of Kentucky Research Foundation Lexington Kentucky
United States Bryan Heart Lincoln Nebraska
United States Cedars Sinai Medical Center Los Angeles California
United States USC Keck School of Medicine Los Angeles California
United States Catholic Medical Center Manchester New Hampshire
United States WellStar Health System, Inc Marietta Georgia
United States Heart Rhythm Specialists McKinney Texas
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 Baptist Health South Florida Miami Florida
United States Minneapolis Heart Institute at Abbott Northwestern Hospital Minneapolis Minnesota
United States Atlantic Health System- Morristown Medical Center Morristown New Jersey
United States NCA Research Institute - Florida Naples Florida
United States Ochsner Clinic Foundation New Orleans Louisiana
United States Weill Cornell Medicine New York New York
United States Valley Clinical Trials- Foothill Cardiology Northridge California
United States Valley Clinical Trials- Northridge Northridge California
United States University of Nebraska Medical Center Omaha Nebraska
United States AdventHealth Orlando Orlando Florida
United States Revival Clinical Research Orlando Florida
United States Kansas City Cardiac Arrhythmia Research LLC Overland Park Kansas
United States Hospital of the University of Pennsylvania Philadelphia Pennsylvania
United States Penn Presbyterian Medical Center Philadelphia Pennsylvania
United States Temple University Hospital Philadelphia Pennsylvania
United States Arizona Heart Rhythm Phoenix Arizona
United States Banner Health- Phoenix Phoenix Arizona
United States Cardiovascular Consultants, Ltd Phoenix Arizona
United States Rutgers New Jersey Medical School Piscataway New Jersey
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States Baylor Scott and White- The Heart Hospital- Plano Plano Texas
United States Providence Heart & Vascular Portland Oregon
United States Tower Health Reading Hospital Reading Pennsylvania
United States Sequoia Hospital Redwood City California
United States Baylor Scott and White Research Institute - Round Rock Round Rock Texas
United States University of California Davis Health Sacramento California
United States Methodist Hospital San Antonio Texas
United States University of California, San Francisco San Francisco California
United States HonorHealth Scottsdale Arizona
United States Swedish Medical Center Seattle Washington
United States Ascension Providence Hospital Southfield Michigan
United States Tallahassee Research Institute Tallahassee Florida
United States Mercy Health- St. Vincent Medical Center LLC Toledo Ohio
United States Pima Heart and Vascular Tucson Arizona
United States Oklahoma Heart Institute Tulsa Oklahoma
United States North Mississippi Medical Center Tupelo Mississippi
United States Peace Health Vancouver Washington
United States MercyOne Iowa Heart West Des Moines Iowa
United States Cleveland Clinic Foundation - Florida Weston Hospital Weston Florida
United States Nuvance Health Wilton Connecticut
United States WellSpan Health York Pennsylvania
United States Trinity health- Michigan Heart Ypsilanti Michigan

Sponsors (1)

Lead Sponsor Collaborator
Impulse Dynamics

Country where clinical trial is conducted

United States, 

References & 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. Erratum In: JACC Heart Fail. 2023 Jan;11(1):132. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 =60%. 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
Primary 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
Primary 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
Primary 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
See also
  Status Clinical Trial Phase
Recruiting NCT05196659 - Collaborative Quality Improvement (C-QIP) Study N/A
Recruiting NCT05654272 - Development of CIRC Technologies
Recruiting NCT05650307 - CV Imaging of Metabolic Interventions
Active, not recruiting NCT05896904 - Clinical Comparison of Patients With Transthyretin Cardiac Amyloidosis and Patients With Heart Failure With Reduced Ejection Fraction N/A
Completed NCT05077293 - Building Electronic Tools To Enhance and Reinforce Cardiovascular Recommendations - Heart Failure
Recruiting NCT05631275 - The Role of Bioimpedance Analysis in Patients With Chronic Heart Failure and Systolic Ventricular Dysfunction
Enrolling by invitation NCT05564572 - Randomized Implementation of Routine Patient-Reported Health Status Assessment Among Heart Failure Patients in Stanford Cardiology N/A
Enrolling by invitation NCT05009706 - Self-care in Older Frail Persons With Heart Failure Intervention N/A
Recruiting NCT04177199 - What is the Workload Burden Associated With Using the Triage HF+ Care Pathway?
Terminated NCT03615469 - Building Strength Through Rehabilitation for Heart Failure Patients (BISTRO-STUDY) N/A
Recruiting NCT06340048 - Epicardial Injection of hiPSC-CMs to Treat Severe Chronic Ischemic Heart Failure Phase 1/Phase 2
Recruiting NCT05679713 - Next-generation, Integrative, and Personalized Risk Assessment to Prevent Recurrent Heart Failure Events: the ORACLE Study
Completed NCT04254328 - The Effectiveness of Nintendo Wii Fit and Inspiratory Muscle Training in Older Patients With Heart Failure N/A
Completed NCT03549169 - Decision Making for the Management the Symptoms in Adults of Heart Failure N/A
Recruiting NCT05572814 - Transform: Teaching, Technology, and Teams N/A
Enrolling by invitation NCT05538611 - Effect Evaluation of Chain Quality Control Management on Patients With Heart Failure
Recruiting NCT04262830 - Cancer Therapy Effects on the Heart
Completed NCT06026683 - Conduction System Stimulation to Avoid Left Ventricle Dysfunction N/A
Withdrawn NCT03091998 - Subcu Administration of CD-NP in Heart Failure Patients With Left Ventricular Assist Device Support Phase 1
Recruiting NCT05564689 - Absolute Coronary Flow in Patients With Heart Failure With Reduced Ejection Fraction and Left Bundle Branch Block With Cardiac Resynchronization Therapy