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

• ClinicalTrials.gov Identifier: NCT05064709
• Recruitment Status: Recruiting
• First Posted: October 1, 2021
• Last Update Posted: April 17, 2024
• Sponsor: Impulse Dynamics
• Information provided by (Responsible Party): Impulse Dynamics

Tracking Information

• First Submitted Date: September 21, 2021
• First Posted Date: October 1, 2021
• Last Update Posted Date: April 17, 2024
• Actual Study Start Date: February 3, 2022
• Estimated Primary Completion Date: February 1, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 30, 2021)

• 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 ≤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.
• 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.
• 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.
• 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.

• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Assessment of CCM in HF With Higher Ejection Fraction
• Official Title: Assessment of Implantable CCM in the Heart Failure Group With Higher Ejection Fraction
• 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 ≤60%.

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 ≤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.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multicenter, multi-national, randomized, quadruple-blind, sham controlled, 2-part, embedded IDE clinical trial

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

In addition to the subject, the entire site research team, the implanting physician, the Clinical Events Committee (CEC), and the clinical study monitors will all be blinded to the treatment assignment. Site research staff and Impulse Dynamics monitoring personnel will not have viewing rights to the randomization assignment.

Primary Purpose: Treatment

Condition

• 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

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.
  Other Name: CCM Group (CCM ON)
• 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 Name: Sham Group (CCM OFF)

Study Arms

• Experimental: CCM Group (CCM ON)
  CCM therapy will be turned on in 2/3 of the subjects for the entire duration of the study.
  Intervention: Device: Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System
• 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.
  Intervention: Device: OPTIMIZER™ Smart Mini System

Publications *

• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 30, 2021): 1500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: February 1, 2026
• Estimated Primary Completion Date: February 1, 2025 (Final data collection date for primary outcome measure)

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 ≤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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Maria Fernanda Villarreal, MD; 8453592389; aimhigher@impulsedynamics.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05064709
• Other Study ID Numbers: CA_CP_340
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Impulse Dynamics
• Original Responsible Party: Same as current
• Current Study Sponsor: Impulse Dynamics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

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

• PRS Account: Impulse Dynamics
• Verification Date: September 2023