Clinical trial NCT05064709: Assessment of CCM in HF With Higher Ejection Fraction
Official title: Assessment of Implantable CCM in the Heart Failure Group With Higher Ejection Fraction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: 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
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
Lead sponsor: Impulse Dynamics
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 1500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicenter, multi-national, randomized, quadruple-blind, sham controlled, 2-part, embedded IDE clinical trial
Primary purpose: TREATMENT

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%.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part 1 Efficacy Endpoint - Change in 6-minute walk distance (6MWD) from baseline to 6 months.
timeFrame: 6 months
measure: 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).
timeFrame: 6 months
measure: Part 1 Safety Endpoint - The incidence of Optimizer device- or procedure-related complications within the first 12 months after implant
timeFrame: 12 months
measure: Part 2 Endpoint - The hierarchical composite of mortality, morbidity, and health status outcomes (KCCQ CSS).
timeFrame: 18 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Grandview Medical Group Research, LLC
state: Alabama
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Mesa
country: United States
facility: CardioVascular Associates of Mesa
state: Arizona
city: Mesa
country: United States
facility: Chan Heart Rhythm Institute
state: Arizona
city: Mesa
country: United States
facility: Southwest Cardiovascular Associates
state: Arizona
city: Phoenix
country: United States
facility: Banner Health- Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Arizona Heart Rhythm
state: Arizona
city: Phoenix
country: United States
facility: Cardiovascular Consultants, Ltd
state: Arizona
city: Scottsdale
country: United States
facility: HonorHealth
state: Arizona
city: Tuscon
country: United States
facility: Pima Heart and Vascular
state: Arizona
city: Concord
country: United States
facility: John Muir Health
state: California
city: Fairfield
country: United States
facility: Northbay Heart and Vascular
state: California
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: USC Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials Pasadena
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials- Northridge
state: California
city: Redwood City
country: United States
facility: Sequoia Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Health
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Hartford
country: United States
facility: Hartford Healthcare
state: Connecticut
city: Wilton
country: United States
facility: Nuvance Health
state: Connecticut
city: Atlantis
country: United States
facility: HCA Florida JFK Hospital
state: Florida
city: Cutler Bay
country: United States
facility: Nouvelle Clinical Research LLC
state: Florida
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Fort Lauderdale
country: United States
facility: Broward Health
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Miami
country: United States
facility: Baptist Health South Florida
state: Florida
city: Naples
country: United States
facility: NCA Research Institute - Florida
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Orlando
country: United States
facility: Revival Clinical Research
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Foundation - Florida Weston Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Healthcare
state: Georgia
city: Marietta
country: United States
facility: WellStar Health System, Inc
state: Georgia
city: Indianapolis
country: United States
facility: Franciscan Health Indianapolis
state: Indiana
city: Indianapolis
country: United States
facility: Ascension Medical Group St. Vincent
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: West Des Moines
country: United States
facility: MercyOne Iowa Heart
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Overland Park
country: United States
facility: Kansas City Cardiac Arrhythmia Research LLC
state: Kansas
city: Lexington
country: United States
facility: Baptist Health Lexington
state: Kentucky
city: Lexington
country: United States
facility: University of Kentucky Research Foundation
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Ascension St. John
state: Michigan
city: Southfield
country: United States
facility: Ascension Providence Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Trinity health- Michigan Heart
state: Michigan
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute at Abbott Northwestern Hospital
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Bridgeton
country: United States
facility: St. Louis Heart and Vascular
state: Missouri
city: Chesterfield
country: United States
facility: St. Luke&#39;s Hospital
state: Missouri
city: Kansas City
country: United States
facility: St. Lukes Hospital Kansas City (Mid America Heart Institute)
state: Missouri
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Camden
country: United States
facility: Our Lady of Lourdes
state: New Jersey
city: Edison
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Edison
country: United States
facility: Jersey Shore University Medical Center
state: New Jersey
city: Haddon Heights
country: United States
facility: Cooper Hospital- Cardiovascular Associates of Delaware Valley
state: New Jersey
city: Morristown
country: United States
facility: Atlantic Health System- Morristown Medical Center
state: New Jersey
city: Piscataway
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Charlotte
country: United States
facility: Sanger Heart and Vascular
state: North Carolina
city: Cincinnati
country: United States
facility: TriHealth Bethesda
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Toledo
country: United States
facility: Mercy Health- St. Vincent Medical Center LLC
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Heart Institute
state: Oklahoma
city: Tulsa
country: United States
facility: St. Francis Hospital - Tulsa
state: Oklahoma
city: Portland
country: United States
facility: Providence Heart & Vascular
state: Oregon
city: Bryn Mawr
country: United States
facility: Bryn Mawr Medical Specialists Association
state: Pennsylvania
city: Harrisburg
country: United States
facility: UPMC Pinnacle Harrisburg
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical City
state: Pennsylvania
city: Lancaster
country: United States
facility: Lancaster General Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Reading
country: United States
facility: Tower Health Reading Hospital
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Upstate
state: South Carolina
city: Greenville
country: United States
facility: Bon Secours Upstate Cardiology
state: South Carolina
city: Germantown
country: United States
facility: The Stern Cardiovascular Foundation
state: Tennessee
city: Austin
country: United States
facility: Texas Cardiac Arrhythmia Research Foundation
state: Texas
city: Austin
country: United States
facility: Ascension Seton
state: Texas
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Dallas
country: United States
facility: HCA Medical City Dallas
state: Texas
city: Fort Worth
country: United States
facility: Baylor Scott White- All Saints- Fort Worth
state: Texas
city: Fort Worth
country: United States
facility: Medical City Fort Worth Hospital
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Houston Methodist
state: Texas
city: Houston
country: United States
facility: Memorial Hermann Texas Medical Center
state: Texas
city: McKinney
country: United States
facility: Heart Rhythm Specialists
state: Texas
city: Plano
country: United States
facility: Baylor Scott and White- The Heart Hospital- Plano
state: Texas
city: Round Rock
country: United States
facility: Baylor Scott and White Research Institute - Round Rock
state: Texas
city: San Antonio
country: United States
facility: Methodist Hospital
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Vancouver
country: United States
facility: Peace Health
state: Washington
Study officials:
affiliation: Baylor Scott and White Research Institute, Dallas, Texas
name: Javed Butler, MD, MPH, MBA
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA
name: Oussama Wazni, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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.