Assessment of CCM in HF With Higher Ejection Fraction

Heart Failure Clinical Trial

— AIM HIGHer  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05064709
• Other study ID #: CA_CP_340
• Status: Recruiting
• Phase: N/A
• 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
• 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;

Related Conditions & MeSH terms

• Diastolic Heart Failure
• Heart Failure
• Heart Failure With Mid Range Ejection Fraction
• Heart Failure With Preserved Ejection Fraction
• Heart Failure, Diastolic

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	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