CCM Device for Heart Failure

(INTEGRA-D Trial)

Recruiting at 61 trial locations

Overseen By Gary Cranke

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Impulse Dynamics

Must be taking: Guideline-directed therapy

Disqualifiers: Severe AI, AS, MS, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

300 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should already be on guideline-directed medical therapy for heart failure, so you may need to continue those medications.

How is the CCM Device for Heart Failure treatment different from other treatments?

The CCM Device for Heart Failure, specifically the OPTIMIZER® Integra CCM-D System, is unique because it uses electrical signals to improve heart function in patients who do not qualify for other device therapies like cardiac resynchronization therapy (CRT). It is implanted in a minimally invasive way and works by enhancing the heart's contractility without causing additional heartbeats, improving exercise tolerance and quality of life. ^{1 2 3 4 5}

Research Team

Niraj Varma, MD

Principal Investigator

The Cleveland Clinic

Nir Uriel, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults over 18 with heart failure (HFrEF) and a left ventricular ejection fraction (LVEF) of 40% or less, who are symptomatic despite treatment but don't qualify for cardiac resynchronization therapy. They must not be pregnant, have severe valve disease, unstable angina, other major medical conditions like end-stage renal disease, or be in another device/drug study.

Inclusion Criteria

I have a type of heart muscle disease and it's been over 40 days since my last heart attack, if I had one.

You have been recommended to have an implantable cardioverter defibrillator (ICD) because of your heart condition.

I am on standard treatment for heart failure.

Exclusion Criteria

Pregnant or planning to become pregnant during the study

I have not had unstable chest pain in the last 30 days.

You have a mechanical tricuspid valve implanted.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Implantation

Eligible subjects are implanted with the CCM-D System, and a subset is induced into ventricular fibrillation during the procedure

1 day

1 visit (in-person)

Initial Follow-up

Evaluate device-related complications and inappropriate ICD shocks

6 months

Regular visits (in-person and virtual)

Long-term Follow-up

Monitor inappropriate shock rate, device effectiveness, and battery longevity

2 years

Regular visits (in-person and virtual)

Treatment Details

Interventions

• OPTIMIZER® Integra CCM-D System

Trial Overview The OPTIMIZER® Integra CCM-D System is being tested to see if it can safely and effectively manage life-threatening rapid heartbeats in patients with advanced heart failure who aren't candidates for certain other therapies. The system will be implanted and monitored over at least two years.

Participant Groups

Group I: CCM-D Implant Experimental Treatment 1 Intervention

The subject is implanted with the CCM-D device.

OPTIMIZER® Integra CCM-D System is already approved in United States, European Union for the following indications:

Approved in United States as Optimizer System for:

• Moderate to severe chronic heart failure in patients who remain symptomatic despite guideline-directed medical therapy, are not indicated for cardiac resynchronization therapy, and have a left ventricular ejection fraction ranging from 25 to 45 percent

Approved in European Union as Optimizer System for:

• Moderate to severe chronic heart failure in patients who remain symptomatic despite guideline-directed medical therapy, are not indicated for cardiac resynchronization therapy, and have a left ventricular ejection fraction ranging from 25 to 45 percent

Who Is Running the Clinical Trial?

Impulse Dynamics

Lead Sponsor

Trials

14

Recruited

3,800+

Findings from Research

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]

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]

In a study of 70 heart failure patients treated with cardiac contractility modulation (CCM) over an average follow-up of 2.8 years, the QRS duration remained stable, indicating that CCM therapy may prevent the worsening of intra-ventricular conduction associated with heart failure.

Unlike other heart failure treatments that typically show an increase in QRS duration over time, CCM therapy appears to maintain QRS duration, suggesting it may have long-term safety benefits and potentially improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long term impact of cardiac contractility modulation on QRS duration. Röger, S., Michels, J., Heggemann, F., et al.[2014]

Cardiac contractility modulation (CCM) therapy is effective for patients with systolic heart failure, improving peak VO2, quality of life, and exercise tolerance, making it a valuable addition to existing treatments like implantable cardioverter defibrillators (ICDs).

CCM therapy is recommended for symptomatic patients with a left ventricular ejection fraction of 35% or less, but it is contraindicated in those with atrial fibrillation, high-grade arrhythmias, or significant AV block, highlighting the importance of patient selection for safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treating congestive heart failure with cardiac contractility modulation (CCM) : possibilities and study overview]. Tönnis, T., Kuck, KH.[2021]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Optimizer Smart in the treatment of moderate-to-severe chronic heart failure. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Optimizer Smart System for the treatment of chronic heart failure: Overview of its safety and efficacy. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Long term impact of cardiac contractility modulation on QRS duration. [2014]

4. Germany pubmed.ncbi.nlm.nih.gov

[Treating congestive heart failure with cardiac contractility modulation (CCM) : possibilities and study overview]. [2021]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term survival with Cardiac Contractility Modulation in patients with NYHA II or III symptoms and normal QRS duration. [2016]