CCM Therapy for Heart Failure

(AIM HIGHer Trial)

Recruiting at 85 trial locations

Overseen By Rachael Riccitello

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Impulse Dynamics

Must be taking: Loop diuretics

Disqualifiers: Dialysis, Cancer treatment, Heart surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

1500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Cardiac Contractility Modulation (CCM) therapy for people with heart failure. The researchers aim to determine if CCM therapy can improve heart function in those with a specific type of heart failure, where the heart's pumping ability is moderately reduced (between 40% and 70%). Participants will receive either active CCM therapy or a placebo (inactive treatment) for a period and then switch to active therapy. Individuals experiencing heart failure symptoms, who have had a related hospital visit in the past year, and are on consistent heart medication might be suitable for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research and potentially benefit from an innovative treatment.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of oral loop diuretics for at least 30 days before joining. It doesn't specify if you need to stop other medications, so it's best to discuss with the trial team.

What prior data suggests that Cardiac Contractility Modulation therapy is safe for heart failure patients?

Research shows that Cardiac Contractility Modulation (CCM) therapy is generally well-tolerated by people with heart failure. The OPTIMIZER™ Smart Mini System provides this therapy. Studies indicate that the FDA has approved this therapy for treating heart failure, suggesting it is reasonably safe. However, one study noted that specific safety details, such as certain side effects, weren't always reported. While the therapy is approved and considered safe, some specific side effects might not be fully detailed in all studies. Overall, CCM therapy appears promising for managing heart failure, with a reassuring safety profile based on its FDA approval. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Cardiac Contractility Modulation (CCM) Therapy because it offers a novel approach to treating heart failure. Unlike traditional treatments that often focus on managing symptoms or reducing the workload on the heart, CCM Therapy enhances the heart's contractility through electrical pulses delivered by the OPTIMIZER™ Smart Mini System. This unique mechanism targets the heart's natural contractions, potentially improving its pumping ability without the need for more invasive procedures or medications. This can lead to better patient outcomes and a higher quality of life for those with heart failure.

What evidence suggests that Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System could be effective for heart failure?

Research shows that Cardiac Contractility Modulation (CCM) therapy could be beneficial for treating heart failure. In this trial, participants in the CCM Group will receive CCM therapy, which studies have found improves heart function, enhances quality of life, and increases exercise capacity. People using the CCM device have experienced better heart pumping and overall heart health. Clinical data also show that CCM therapy can significantly improve the heart's ability to pump blood in patients with heart failure. The FDA has approved this therapy, supporting its effectiveness for treating heart failure. Meanwhile, participants in the Sham Group will initially receive inactive therapy for the first 18 months before transitioning to active CCM therapy for the remainder of the study. ^{1 2 3 6 7}

Who Is on the Research Team?

Oussama Wazni, MD, MBA

Principal Investigator

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA

Javed Butler, MD, MPH, MBA

Principal Investigator

Baylor Scott and White Research Institute, Dallas, Texas

Are You a Good Fit for This Trial?

Adults diagnosed with symptomatic heart failure, who have been hospitalized for it or needed urgent IV therapy in the past year, and have a left ventricular ejection fraction (LVEF) between 40% and 60%. They must be on stable diuretic treatment. Exclusions include pregnancy plans during the study, certain heart rates, complex heart conditions, inability to walk specific distances, recent acute heart issues or procedures.

Inclusion Criteria

I am a man or a non-pregnant woman aged 21 or older.

I was hospitalized for heart failure or needed urgent IV therapy for it in the past year.

Your NT-proBNP levels are too high, or your BNP levels are too high, especially if you have atrial tachyarrhythmia.

Exclusion Criteria

I can't walk 100 meters but can walk more than 450 meters in a 6-minute walk test.

You have trouble exercising because of a health condition other than heart failure, and it makes you feel very short of breath or tired.

My heart-related quality of life score is above 85.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Testing and Implantation

All eligible subjects will undergo baseline testing and be implanted with the Optimizer System

1-2 weeks

1 visit (in-person)

Treatment Part I

CCM therapy is evaluated for safety and effectiveness based on functional capacity and health status

6 months

Regular visits (in-person)

Treatment Part II

CCM therapy is evaluated for safety and effectiveness based on clinical outcome data

12 months

Regular visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System
• OPTIMIZER™ Smart Mini System
• Sham Therapy

Trial Overview

The AIM HIGHer trial is testing the safety and effectiveness of Cardiac Contractility Modulation (CCM) therapy using the OPTIMIZER™ Smart Mini System in patients with moderate levels of heart failure (LVEF ≥40% ≤60%).

How Is the Trial Designed?

Group I: CCM Group (CCM ON) Experimental Treatment 1 Intervention

CCM therapy will be turned on in 2/3 of the subjects for the entire duration of the study.

Group II: Sham Group (CCM OFF) Placebo Group 1 Intervention

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.

Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System is already approved in United States, European Union for the following indications:

Approved in United States as Optimizer Smart Mini for:

• Heart failure in NYHA Class III patients with LVEF ranging from 25% to 45%, who remain symptomatic despite guideline directed medical therapy and are not indicated for CRT

Approved in European Union as Optimizer Smart Mini for:

• Heart failure in NYHA Class III patients with LVEF ranging from 25% to 45%, who remain symptomatic despite guideline directed medical therapy and are not indicated for CRT

Who Is Running the Clinical Trial?

Impulse Dynamics

Lead Sponsor

Trials

14

Recruited

3,800+

Published Research Related to This Trial

Cardiac contractility modulation (CCM) therapy showed similar effectiveness in reducing left ventricular end-systolic volume (LVESV) compared to cardiac resynchronization therapy (CRT) in patients with mildly prolonged QRS duration, indicating it can be a viable alternative for certain heart failure patients.

However, CRT was more effective in patients with very wide QRS durations, achieving a greater reduction in LVESV and a higher responder rate, suggesting that the choice of therapy may depend on the specific characteristics of the patient's heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of left ventricular reverse remodeling induced by cardiac contractility modulation and cardiac resynchronization therapy in heart failure patients with different QRS durations. Zhang, Q., Chan, YS., Liang, YJ., et al.[2013]

In a retrospective study of 68 heart failure patients treated with Cardiac Contractility Modulation (CCM), long-term mortality rates were significantly lower than predicted by the Seattle Heart Failure Model, suggesting a potential survival benefit from this treatment.

The study followed patients for an average of 4.5 years, showing that CCM may improve survival outcomes in heart failure patients with NYHA II-III symptoms and a QRS duration of ≤130ms, indicating its efficacy in this specific population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with Cardiac Contractility Modulation in patients with NYHA II or III symptoms and normal QRS duration. Kloppe, A., Lawo, T., Mijic, D., et al.[2016]

In a study of 174 patients with chronic heart failure receiving cardiac contractility modulation (CCM) therapy, those with non-ischemic cardiomyopathy (NICM) showed significant improvements in left ventricular ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) after 3 and 5 years, respectively.

Patients with ischemic cardiomyopathy (ICM) had lower mortality rates than predicted at 3 years, indicating that CCM therapy may provide a survival benefit for this group, although overall mortality rates were similar between ICM and NICM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Contractility Modulation in Patients with Ischemic versus Non-ischemic Cardiomyopathy: Results from the MAINTAINED Observational Study. Fastner, C., Yuecel, G., Rudic, B., et al.[2021]

Cardiac contractility modulation (CCM) therapy using the Optimizer Smart System is a new, minimally invasive device therapy for heart failure patients who do not qualify for traditional treatments like cardiac resynchronization therapy (CRT).

Initial findings suggest that CCM therapy is safe and feasible for a broad range of heart failure patients, but further large-scale randomized controlled trials are needed to confirm its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizer Smart System for the treatment of chronic heart failure: Overview of its safety and efficacy. Chera, HH., Al-Sadawi, M., Michelakis, N., et al.[2021]

The Optimizer Smart device, which uses cardiac contractility modulation (CCM), is FDA-approved for treating chronic heart failure in patients with a left ventricular ejection fraction (LVEF) between 25% and 45%, offering a new option for those who are symptomatic despite optimal medical therapy.

Clinical trials show that CCM therapy is safe and effective, leading to reduced hospitalizations for heart failure and improved symptoms, quality of life, and functional performance, particularly for patients who do not qualify for traditional cardiac resynchronization therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizer Smart in the treatment of moderate-to-severe chronic heart failure. Campbell, CM., Kahwash, R., Abraham, WT.[2021]

The OPTIMIZER System, which delivers cardiac contractility modulating (CCM) signals, has been successfully used in a patient who did not respond to a cardiac resynchronization therapy device, indicating its potential as a new treatment option for heart failure patients who are non-responders to CRT.

The study demonstrates that the implantation of the OPTIMIZER System is technically feasible and that it can coexist with CRT devices without interference, leading to acute improvements in both hemodynamics and clinical symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First use of cardiac contractility modulation (CCM) in a patient failing CRT therapy: clinical and technical aspects of combined therapies. Butter, C., Meyhöfer, J., Seifert, M., et al.[2011]

Cardiac contractility modulation (CCM) is a promising treatment for patients with moderate to severe systolic heart failure, enhancing heart function without increasing oxygen demand, unlike traditional inotropic drugs.

CCM has been shown to be safe and effective in multicenter studies, providing an alternative for patients who do not respond to optimal medical therapy, regardless of their QRS duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Improving left ventricular contractility by stimulation during the absolute refractory period--cardiac contractility modulation (CCM)]. Seifert, M., Hoffmann, J., Meyhöfer, J., et al.[2021]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11152971/

Cardiac contractility modulation in patients with heart failure

Cardiac contractility modulation in patients with heart failure: The added value of cardiac rehabilitation in identification, management, and follow-up.

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cms.gov

cms.gov/medicare-coverage-database/view/ncacal-decision-memo.aspx?proposed=Y&NCAId=317

Cardiac Contractility Modulation (CCM) for Heart Failure

Use this page to view details for the Proposed Decision Memo for Cardiac Contractility Modulation (CCM) for Heart Failure (CAG-00469N).

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8360159/

Long‐term clinical experience with cardiac contractility ...

Cardiac contractility modulation therapy improved functional status, quality of life, LVEF and, compared to patients' prior history, reduced heart failure ...

4.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCHEARTFAILURE.119.006512

Safety, Performance, and Efficacy of Cardiac Contractility ...

Collectively, the results of these prior randomized studies indicated that CCM improves functional class, quality of life, and exercise ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2772930323011778

Cardiac Contractility Modulation for Heart Failure

Cardiac contractility modulation (CCM) is a Food and Drug Administration-approved device-based therapy for patients with heart failure.

6.

aetna.com

aetna.com/cpb/medical/data/900_999/0930.html

Cardiac Contractility Modulation (CCM) Therapy

The purpose of the Optimizer System post-approval study is to provide long-term safety and effectiveness data for the Optimizer Smart System. The study is a ...

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jscai.org

jscai.org/article/S2772-9303(23)01177-8/fulltext

Cardiac Contractility Modulation for Heart Failure

Cardiac contractility modulation (CCM) is a Food and Drug Administration-approved device-based therapy for patients with heart failure.