Cardiac Contractility Modulation (CCM) Therapy in Subjects With Medically Refractory Heart Failure (IMPULSE-HF)

Cardiac Contractility Modulation (CCM) Therapy in Subjects With Medically Refractory Heart Failure: A Randomized Efficacy Study

The study is designed to substantiate the efficacy of Cardiac Contractility Modulation (CCM) in the heart failure population with ejection fraction ranging between 25 and 45%. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation.

Study Overview

• Status: Terminated
• Conditions: Heart Failure
• Intervention / Treatment: Device: OPTIMIZER; Drug: Optimal medical therapy

Detailed Description

This study will collect efficacy data in a randomized controlled setting, including New York Heart Association (NYHA) class II and III Heart Failure population with baseline ejection fraction (EF) of 25% to 45%.

There is previous evidence related to the beneficial effect of CCM in patients with baseline ejection fraction of <35%. While patients with EF between 35% and 45% were not prospectively studied in the original clinical study initially conducted to support Conformité Européene (CE) Marking of the OPTIMIZER System, recently available data from a randomized study that included such patients show CCM to be safe and effective in this group of patients as well. Furthermore, the literature supports that this population has very similar clinical characteristics, in practice are treated with nearly the same medications, and have similar underlying mechanisms of disease compared to patients with EF <35%. CCM has been successfully used also in patients with EF greater than 35% in routine use and in the FIX-HF-5 study.

Since the system is CE marked and since the population includes patients meeting the approved indication as well as population that has shown to benefit from CCM (EF 35%-45%), the risk involved in performing such a clinical investigation seems acceptable.

The study is designed to substantiate the efficacy of CCM in heart failure patients with EFs in the range of 25%-to-45% (inclusive). This is a prospective, randomized study comparing CCM plus optimal medical therapy (OMT) (Treatment Group) to OMT alone (Control Group) over a 24 week period. The primary endpoint shall be a comparison of changes in Peak VO2, which is an established objective physiological indicator of exercise capacity which is relevant in heart failure device studies. To further improve the accuracy and objectivity of measurements, double assessment of the Peak VO2 will be performed at each of the primary time points. Tests can be performed using upright and semi-supine bicycle ergometer or using treadmill. In sites where more than one option is available, bicycle ergometer is the preferred option. Treadmill is only allowed in case no bicycle is available at the site. Each subject shall be consistently tested using the same method throughout the study. The study is designed in an adaptive manner to ensure proper statistical significance and power of the primary efficacy evaluation.

The study will collect additional (exploratory) efficacy data on the difference between the treatment group and control group in the changes over 24 weeks in predicted survival probability. To evaluate the survival probability, two established models are used: the Seattle Heart Failure Model (SHFM), and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) model . These models use information collected at a certain time point to predict survival probabilities over the following years. The information used for such prediction includes status of the disease (NYHA, Left Ventricular EF (LVEF)), documented medical history and co-morbidities, documented therapies and medications, and standard blood tests values.

Additionally, hospitalization data will be collected from medical records of the site and/or from any other medical records of clinics/hospitals where the patient may have been treated for a timeframe of 12 months before enrollment and until 24 weeks after the Study Start Date (SSD).

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria
    • Universitätsklinik Innere Medizin
• Germany
  • Aachen, Germany
    • Universtitätsklinikum; Medizinische Klinik I
  • Erfurt, Germany
    • Helios Klinikum; 3. Medizinische Klinik
  • Hamburg, Germany
    • Albertinen Krankenhaus
  • Köln, Germany
    • Universitätsklinikum; Kardiologie im Herzzentrum
  • Leipzig, Germany
    • Universität Leipzig; Abteilung für Kardiologie und Angiologie
• Poland
  • Wroclaw, Poland
    • 4th Military Hospital
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Baseline ejection fraction ≥ 25% and ≤45% (as assessed by the site)
• NYHA class II or III (chronic, not transient, heart failure) despite receiving optimal medical therapy for heart failure
• Stable medication for heart failure for at least 30 days based on patient's medical records
• Baseline Peak VO2 ≥ 10 and ≤ 18.5 ml O2/Kg/min (as assessed by the site)

Exclusion Criteria:

• Potentially correctible cause of HF (valvular, congenital, or untreated ischemic heart disease)
• Clinically significant angina pectoris
• Hospitalization for HF requiring the use of inotropic support or IV diuretics within 30 days of enrollment
• PR interval greater than 375 ms
• Permanent or persistent atrial fibrillation/flutter or cardioversion within 30 days of enrollment.
• Exercise tolerance limited by condition other than heart failure (e.g., angina, chronic obstructive pulmonary disease (COPD), peripheral vascular disease, orthopedic or rheumatologic conditions) or unable to perform baseline stress testing
• Scheduled for a coronary artery bypass graft (CABG) or a percutaneous transluminal coronary angioplasty (PTCA) procedure, or CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.
• Biventricular pacing system, or indication for Biventricular pacing system
• Myocardial infarction within 90 days of enrollment.
• Mechanical tricuspid or aortic valves.
• Ventricular assist device
• Prior heart transplant
• Pregnant or planning to become pregnant during the study
• Age below 18
• Subject participating in another study, unrelated to CCM, at the same time (or within 30 days prior to enrollment to this study)
• Subjects on dialysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Device implant; Patients randomized to the treatment group will receive optimal medical therapy for heart failure. and implantation of the OPTIMIZER System.	Device: OPTIMIZER; The OPTIMIZER System delivers non-excitatory cardiac contractility modulation (CCM) signals to the heart that are intended to influence myocardial properties in patients with chronic heart failure. The system has no pacemaker or implantable cardioverter-defibrillator (ICD) functions.; Drug: Optimal medical therapy; OMT using standard heart failure (HF) drugs; Other Names: angiotensin receptor blockers; mineralocorticoid receptor antagonists; angiotensin receptor neprilysin inhibitors
Active Comparator: Optimal medical therapy; Patients randomized to the control group will receive optimal medical therapy for heart failure.	Drug: Optimal medical therapy; OMT using standard heart failure (HF) drugs; Other Names: angiotensin receptor blockers; mineralocorticoid receptor antagonists; angiotensin receptor neprilysin inhibitors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Comparison between the groups of the change in Peak VO2 from baseline to 24 weeks of follow-up.	from baseline to 24 weeks of follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
Comparison of change in quality of life as measure (MLWHFQ), from baseline to 24 weeks of follow-up	from baseline to 24 weeks of follow-up
Comparison of change in NYHA class, from baseline to 24 weeks of follow-up	from baseline to 24 weeks of follow-up
Comparison of change in Peak VO2 from baseline to 24 weeks of follow-up for each of the following subgroups separately: Baseline EF <35% , baseline EF ≥35%	from baseline to 24 weeks of follow-up

Other Outcome Measures

Outcome Measure	Time Frame
Comparison between the groups of the change in SHFM survival prediction model score from baseline to 24 weeks of follow-up	from baseline to 24 weeks of follow-up
Comparison between the groups of the change in MAGGIC survival prediction model score from baseline to 24 weeks of follow-up	from baseline to 24 weeks of follow-up
All-cause mortality	from baseline to 24 weeks of follow-up
Cardiovascular mortality	from baseline to 24 weeks of follow-up
Time to first event - cardiovascular related	from baseline to 24 weeks of follow-up
Time to first event - all causes	from baseline to 24 weeks of follow-up

Collaborators and Investigators

• Sponsor: Impulse Dynamics
• Investigators: Principal Investigator: Gerhard Hindricks, Prof., Herzzentrum Leipzig GmbH

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): February 15, 2018
• Study Completion (Actual): February 15, 2018

Study Registration Dates

• First Submitted: July 20, 2016
• First Submitted That Met QC Criteria: August 4, 2016
• First Posted (Estimate): August 5, 2016

Study Record Updates

• Last Update Posted (Actual): September 2, 2020
• Last Update Submitted That Met QC Criteria: September 1, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Diuretics, Potassium Sparing; Mineralocorticoid Receptor Antagonists; Mineralocorticoids; Angiotensin Receptor Antagonists
• Other Study ID Numbers: ID_CP_OPT2013-026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No