AIM HIGHer: Assessment of CCM in HF With Higher Ejection Fraction

• Sponsor: Impulse Dynamics (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT05064709
• Collaborator: (none)
• Enrollment: 1,500
• Locations: 37
• Arms: 2
• Anticipated Duration (Months): 47.9
• Patients Per Site: 40.5
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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%.

Condition or Disease	Intervention/Treatment	Phase
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	Device: Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System; Device: OPTIMIZER™ Smart Mini System	N/A

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 1500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter, multi-national, randomized, quadruple-blind, sham controlled, 2-part, embedded IDE clinical trialMulticenter, 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
• Official Title: Assessment of Implantable CCM in the Heart Failure Group With Higher Ejection Fraction
• Actual Study Start Date: Feb 3, 2022
• Anticipated Primary Completion Date: Feb 1, 2025
• Anticipated Study Completion Date: Feb 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CCM Group (CCM ON) CCM therapy will be turned on in 2/3 of the subjects for the entire duration of the study.	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 Names: CCM Group (CCM ON)
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.	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 Names: Sham Group (CCM OFF)

Outcome Measures

Primary Outcome Measures

1. Part 1 Efficacy Endpoint - Change in 6-minute walk distance (6MWD) from baseline to 6 months. [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.

2. 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). [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.

3. Part 1 Safety Endpoint - The incidence of Optimizer device- or procedure-related complications within the first 12 months after implant [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.

4. Part 2 Endpoint - The hierarchical composite of mortality, morbidity, and health status outcomes (KCCQ CSS). [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Signed and dated informed consent form;

2. Male or non-pregnant female, 21 years or older;

3. Diagnosed with symptomatic heart failure;

4. LVEF ≥40 and ≤60% (as assessed by echo core lab);

5. Heart failure hospitalization within 12 months prior to study consent OR Urgent heart failure visit requiring IV therapy during the 6 months prior to study consent;

6. Elevated NT-proBNP levels, >200 pg/ml for subjects without atrial tachyarrhythmia (AT) or >600 pg/ml for subjects in AT OR Elevated BNP levels, >75 pg/ml for subjects without AT or >225 pg/ml for subjects in AT;

1. Subjects must be on a stable, scheduled oral loop diuretic treatment (not only PRN) for at least 30 days prior to study consent, unless documented allergy.

Exclusion Criteria:

1. Resting heart rate <50 or >110 bpm;

2. Resting systolic blood pressure <100 or ≥160 mmHg;

3. BMI greater than 40

4. Any moderate or 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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Grandview Medical Group Research, LLC	Birmingham	Alabama	United States	35243
2	CardioVascular Associates of Mesa	Mesa	Arizona	United States	85206
3	Chan Heart Rhythm Institute	Mesa	Arizona	United States	85206
4	Southwest Cardiovascular Associates	Mesa	Arizona	United States	85208
5	Arizona Heart Rhythm	Phoenix	Arizona	United States	85016
6	HonorHealth	Scottsdale	Arizona	United States	85258
7	Pima Heart and Vascular	Tucson	Arizona	United States	85712
8	Valley Clinical Trials- Foothill Cardiology	Northridge	California	United States	91325
9	Valley Clinical Trials- Northridge	Northridge	California	United States	91325
10	University of California, San Francisco	San Francisco	California	United States	94143
11	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
12	Memorial Healthcare System	Hollywood	Florida	United States	33021
13	Baptist Health South Florida	Miami	Florida	United States	33176
14	Piedmont Healthcare	Atlanta	Georgia	United States	30309
15	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
16	Baptist Health Lexington	Lexington	Kentucky	United States	40503
17	Minneapolis Heart Institute at Abbott Northwestern Hospital	Minneapolis	Minnesota	United States	55407
18	St. Louis Heart and Vascular	Bridgeton	Missouri	United States	63044
19	Our Lady of Lourdes	Camden	New Jersey	United States	08103
20	Hackensack University Medical Center	Edison	New Jersey	United States	08837
21	Cooper Hospital- Cardiovascular Associates of Delaware Valley	Haddon Heights	New Jersey	United States	08035
22	Atlantic Health System- Morristown Medical Center	Morristown	New Jersey	United States	07960
23	Weill Cornell Medicine	New York	New York	United States	10021
24	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
25	OhioHealth Research Institute	Columbus	Ohio	United States	43214
26	UPMC Pinnacle Harrisburg	Harrisburg	Pennsylvania	United States	17110
27	Lancaster General Hospital	Lancaster	Pennsylvania	United States	17602
28	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104-6061
29	Tower Health Reading Hospital	Reading	Pennsylvania	United States	19611
30	Prisma Health Upstate	Greenville	South Carolina	United States	29601
31	Texas Cardiac Arrhythmia Research Foundation	Austin	Texas	United States	78705
32	Baylor Scott and White Research Institute	Dallas	Texas	United States	75204
33	HCA Medical City Dallas	Dallas	Texas	United States	75230
34	Baylor Scott White- All Saints- Fort Worth	Fort Worth	Texas	United States	76104
35	Baylor College of Medicine	Houston	Texas	United States	77030
36	Heart Rhythm Specialists	McKinney	Texas	United States	75070
37	Baylor Scott and White- The Heart Hospital- Plano	Plano	Texas	United States	75093

Sponsors and Collaborators

• Impulse Dynamics

Investigators

• Principal Investigator: Javed Butler, MD, MPH, MBA, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
• Principal Investigator: Oussama Wazni, MD, MBA, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA

Study Documents (Full-Text)

None provided.

More Information

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.
• Tschöpe 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 3. doi: 10.1002/ehf2.13126. [Epub ahead of print]
• Tschöpe 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.
• 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.

• Responsible Party: Impulse Dynamics
• ClinicalTrials.gov Identifier: NCT05064709
• Other Study ID Numbers: CA_CP_340
• First Posted: Oct 1, 2021
• Last Update Posted: Aug 25, 2022
• Last Verified: May 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Impulse Dynamics: HFpEF; Heart failure; CCM; CCM therapy; cardiac contractility modulation; symptomatic heart failure; left ventricular ejection fraction; LVEF; Optimizer; Optimizer Smart Mini; Quality of Life
• Additional relevant MeSH terms: Heart Failure; Heart Failure, Diastolic

Study Results

No Results Posted as of Aug 25, 2022