Assessment of Combined CCM and ICD Device in HFrEF (INTEGRA-D)

Assessment of the Safety and Efficacy of a Combined Cardiac Contractility Modulation and Implantable Cardioverter Defibrillator Device for Subjects With Heart Failure and Reduced Ejection Fraction

The goal of this clinical trial is to demonstrate that the OPTIMIZER® Integra CCM-D System (the "CCM-D System") can safely and effective convert induced ventricular fibrillation (VF) and spontaneous ventricular tachycardia and/or ventricular fibrillation (VT/VF) episodes in subjects with Stage C or D heart failure who remain symptomatic despite being on guideline-directed medical therapy (GDMT), are not indicated for cardiac resynchronization therapy (CRT), and have heart failure with reduced left ventricular ejection fraction (LVEF ≤40%).

Eligible subjects will be implanted with the CCM-D System. A subset of subjects will be induced into ventricular fibrillation "on the table" in the implant procedure room. During the follow-up period, inappropriate shock rate and device-related complications will be evaluated. The follow-up period is expected to last at least two years.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure; Arrhythmias, Cardiac; Ventricular Fibrillation; Ventricular Tachycardia; Implantable Defibrillator User; Heart Failure With Reduced Ejection Fraction; Ischemic Cardiomyopathy; Sudden Cardiac Arrest; Non-ischemic Cardiomyopathy; CCM Therapy
• Intervention / Treatment: Device: OPTIMIZER® Integra CCM-D System (Treatment Arm)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Phoenix Heart
    • Mesa, Arizona, United States, 85206
      • CardioVascular Associates of Mesa
    • Mesa, Arizona, United States, 85208
      • Southwest Cardiovascular Associates
    • Phoenix, Arizona, United States, 85016
      • Arizona Heart Rhythm
    • Phoenix, Arizona, United States, 85032
      • CVC Cardiovascular Consultants
    • Phoenix, Arizona, United States, 85306
      • Phoenix Heart
    • Scottsdale, Arizona, United States, 85258
      • Honor Health
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford HealthCare
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward Health Medical Center
    • Miami, Florida, United States, 33173
      • Baptist Health South Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center Miami Beach
    • Orlando, Florida, United States, 32803
      • Advent Health Orlando
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • University of Kansas Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Hospital
    • St Louis, Missouri, United States, 63136
      • St. Louis Heart and Vascular
    • St Louis, Missouri, United States, 63106
      • St. Louis VA
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart and Lung Center
    • Cherry Hill, New Jersey, United States, 08034
      • Virtua
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
    • Haddon Heights, New Jersey, United States, 08035
      • The Heart House - Cardiovascular Associates of the Delaware Valley
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10016
      • NYU Langone
    • New York, New York, United States, 10029
      • Mount Sinai New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center / NewYork-Presbyterian
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Sanger Heart and Vascular Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Louis Stokes Cleveland VA Medical Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • St. Francis Tulsa
  • Oregon
    • Portland, Oregon, United States, 97239
      • Portland VA Medical Center
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's Bethlehem
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Medical Specialists Association
    • Lancaster, Pennsylvania, United States, 17602
      • Lancaster General Hospital
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Presbyterian
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny General Hospital
    • Pittsburgh, Pennsylvania, United States, 15219
      • University of Pittsburgh Medical Center
  • South Carolina
    • Greenville, South Carolina, United States, 29601
      • Prisma Health
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Cardiac Arrhythmia Research Foundation
    • Dallas, Texas, United States, 75390
      • UT Southwestern
    • Dallas, Texas, United States, 75230
      • Medical City Dallas
    • Fort Worth, Texas, United States, 76104
      • Medical City Fort Worth
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Houston, Texas, United States, 77030
      • Houston VA Hospital
    • Houston, Texas, United States, 77030
      • UT Memorial Hermann
    • Tyler, Texas, United States, 75702
      • Christus Trinity Clinic
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Centra Health
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23225
      • Chippenham Hospital
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish
    • Seattle, Washington, United States, 98108
      • Seattle VA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Individuals must meet all the following:

1. Patient is aged 18 years or older;
2. Patient meets the Stage C or D criteria of the Universal Definition of Heart Failure ;
3. Patient has HFrEF (LVEF ≤40%);
4. Patient is on GDMT for heart failure;
5. Patient has a Class I or Class II indication for an ICD
6. Patient has a reasonable expectation of meaningful survival of > 1 year;
7. Patient has either non-ischemic cardiomyopathy or ischemic cardiomyopathy and is at least 40 days post-MI, if an MI occurred;
8. Patient is willing to give informed consent, available for scheduled study follow-up visits, and able to complete all testing described in the study protocol at the investigational site location.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Patients should not have severe AI or AS, and should not have MS; additionally, patients undergoing DE testing should not have severe MR;
2. Patients who have undergone mitral valve repair or clip within 90 days prior to study consent;
3. Cardiac surgery within 90 days or a PCI procedure within 30 days prior to study consent;
4. Prior heart transplant or ventricular assist device;
5. Implanted mechanical tricuspid valve;
6. PR interval greater than 375ms or advanced AV block;
7. In situ S-ICD, pacemaker, or CRT device;
8. Indicated for CRT;
9. End stage renal disease, currently on dialysis, or with other major medical disorder (e.g. liver failure, terminal cancer);
10. Indicated for permanent bradyarrhythmia pacing;
11. Unstable angina pectoris within 30 days prior to study consent;
12. Pregnant or planning to become pregnant during the study;
13. Participating in another cardiac investigational device or drug study at the same time (or within 30 days prior to study consent); Note: Registries and other observational studies are acceptable.
14. Other criteria that preclude Optimizer INTEGRA CCM-D implantation and/or CCM therapy, as determined by Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CCM-D Implant; The subject is implanted with the CCM-D device.

Device: OPTIMIZER® Integra CCM-D System (Treatment Arm); The CCM-D System is an implantable cardiac device system that combines cardiac contractility modulation and implantable cardioverter defibrillator (ICD) modules into one device. CCM-D is also known as a "Cardiac Contractility Modulation - Defibrillator". All 300 subjects will be implanted with the CCM-D System and followed for a period of at least two years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Effectiveness in Converting Induced Ventricular Fibrillation (Primary Efficacy Objective)	Evaluate the device effectiveness in converting induced VF at the time of implantation.	Implant
Device-related Complications (Primary Safety Objective)	Evaluate device-related complications through 6-months (excluding lead-related complications).	Implant to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inappropriate Shock Rate out to 6-months (Secondary Safety Objective)	Evaluate the incidence of inappropriate ICD shocks through the time when the last subject enrolled completes the 6-month visit.	Implant to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inappropriate Shock Rate out to 2-years	Evaluate the device effectiveness in converting spontaneous VT/VF through the time when the last subject enrolled completes the 6-month visit. Each subject will be followed for 2-years after implant to capture additional spontaneous episodes that may occur.	Implant to 2 years
Charging non-compliance	Evaluate subject charging non-compliance defined as >14 days between interval charging sessions, overall and frequency of non-compliance in the same subject.	Implant to 2 years
Longitudinal levels of activity	Track longitudinal levels of activity weekly via OPTIhome (when available) and identification of trends.	Implant to 2 years
Battery degradation and longevity	Assess battery degradation and longevity either remotely or during an in-person follow-up at 2 years (+/- 60 days) by recording QHR battery voltage as measured by the Integra CCM-D IPG. The measurement under nominal conditions is expected to be 2.85V or higher, consistent with a 20-year device longevity.	Implant to 2 years
Compare worsening heart failure events pre- and post-implant	Track unscheduled cardiovascular-related healthcare encounters from 12 months prior to implant, if available, to 12 months post-implant	12 months prior to implant and 12 months post-implant
All-cause mortality	Assess all-cause mortality using Seattle Heart Failure Model (SHFM) and comorbidity burden as a predictive comparator at 1 year and 2 years post-implant	1 and 2 years post-implant
Kansas City Cardiomyopathy Questionnaire (KCCQ)	Compare change in subject's perception of their heart failure symptoms, as measured by KCCQ, from baseline to 6 months.	Baseline to 6-months
EQ-5D-5L	Compare change in subject's perception of their health status, as measured by the EQ-5D-5L, from baseline to 6 months.	Baseline to 6-months
Six Minute Walk Distance (6MWD)	Compare change in functional capacity, as measured by 6MWD, from baseline to 6 months.	Baseline to 6 months

Collaborators and Investigators

• Sponsor: Impulse Dynamics
• Investigators: Principal Investigator: Nir Uriel, MD, Columbia University; Principal Investigator: Niraj Varma, MD, PhD, The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: May 3, 2023
• First Posted (Actual): May 11, 2023

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Ventricular fibrillation; Stage C Heart Failure; Ventricular tachycardia; HFrEF; Implantable cardioverter defibrillator; Sudden cardiac arrest; Stage D Heart Failure; Defibrillation Efficacy Testing; Induced Ventricular Fibrillation
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Death; Heart Arrest; Death, Sudden; Tachycardia; Pathological Conditions, Signs and Symptoms; Heart Failure; Death, Sudden, Cardiac; Tachycardia, Ventricular; Arrhythmias, Cardiac; Ventricular Fibrillation
• Other Study ID Numbers: RG_PRO_345

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