A Study Evaluating an Implantable Cardiac Microcurrent Device in Patients With Chronic Heart Failure

A Double Blind, Randomized, Sham Controlled Parallel-group Study, Evaluating the Performance of the Berlin Heals Cardiac Microcurrent (C-MIC) System With a Subcutaneously Implanted Left Ventricular Lead in Patients With Chronic Heart Failure With Reduced Ejection Fraction Stratified by Disease Etiology

This study evaluates the safety and performance/effectiveness of the C-MIC System, an active implantable medical device designed to treat patients with heart failure with reduced ejection fraction (HFrEF). The system delivers a non-excitatory, constant direct electrical microcurrent (DC) to the heart with the aim of improving cardiac function.

The C-MIC System is intended for use in patients with ischemic or non-ischemic dilated cardiomyopathy who have symptomatic, ambulatory heart failure despite receiving guideline-directed medical therapy. Eligible patients must have a left ventricular ejection fraction (LVEF) between ≥20% and ≤40%.

The device is implanted in the catheterization laboratory using a minimally invasive procedure that does not require open-heart surgery. Following implantation, patients receive C-MIC Therapy for a duration of six months. The therapy is designed to improve left ventricular performance, as well as functional capacity and patient well-being, including 6-minute walk distance, quality of life, and New York Heart Association (NYHA) functional class.

INCLUSION CRITERIA

• Only for Stratum 1: Patients with HFrEF with non-ischemic disease etiology1

• Only for Stratum 2: Patients with HFrEF with ischemic disease etiology. All Participants

  1. Informed consent in writing obtained from patient.

  2. Ambulatory patients with symptomatic chronic heart failure in NYHA functional class II-IV at the time of screening lasting for more than 1 year based on the date of diagnosis. Participants in NYHA II at screening must have one documented episode of NYHA III during the prior 6 months with either hospitalization or increase of heart failure medication dosage.

  3. Documented worsening heart failure episode within 12 months prior to screening, defined as HF hospitalization, requirement for intravenous diuretic therapy, or escalation of oral diuretic therapy due to clinically significant worsening HF symptoms requiring medical intervention, as evidenced by source documentation.

  4. Patients who have a baseline LVEF of ≥ 20 % and ≤ 40 % in echocardiography as assessed by the core-lab within 30 days prior to device implantation.

  5. Female and male patients aged 18 years to ≤ 80 years.

  6. Patients receiving appropriate, stable guideline-directed medical therapy for heart failure for at least 90 days prior to screening. [Note: Stable therapy is defined as no more than a 50 % increase or 50 % decrease in dose. If a patient is unable to take guideline recommended doses of heart failure medication, documented evidence must be available.]

  7. Patients who are able to perform a 6-minute walk test. At screening, the 6-minute walk test distance is between 100 and 450 m.

  8. Body habitus that, in the opinion of the Investigator, permits safe and feasible implantation of the C-MIC System, including adequate anatomical access and visualization required for the procedure

     EXCLUSION CRITERIA All Participants

• Patients who are not likely to experience improvement of their chronic heart failure by the microcurrent therapy, because the causes of the disease cannot be influenced even if the patients fulfill the indication for use of the device or if the therapy with the C MIC System is not possible or might be associated with unknown risks:

  1. Patients who have a potentially correctible cause of heart failure, such as severe valvular heart disease or congenital heart disease.
  2. Patients with an indication for a CRT system according to current guidelines.
  3. Patients who have been hospitalized for heart failure which required the use of inotropic support within 90 days before screening.
  4. Patients with systolic blood pressure (SBP) above 150 mmHg and diastolic blood pressure (DBP) above 90 mmHg despite optimal antihypertensive medical treatment.
  5. Patients with SBP < 90 mmHg at screening while not receiving vasopressor therapy, as assessed by the Investigator.
  6. Patients with hemoglobin blood level < 11 g/dL.
  7. Patients with primary severe pulmonary hypertension defined as estimated systolic pulmonary artery pressure (SPAP) > 80 mmHg on screening echocardiography.
  8. Patients who have genetic connective tissue disease (for example Marfan syndrome).
  9. Patients with a prosthetic tricuspid valve.
  10. Patients in whom access for implantation of the leads cannot be obtained (i.e. known venous occlusion, post radiation therapy).
  11. Patients with other anatomical features (e.g., thoracic deformities) that, in the investigator's judgment, would make straightforward device placement unlikely.
  12. Patients with a pacemaker, an ICD system, a CRT system or with a CCM system* [* In case the patient requires a pacemaker or has a CCM device, the impulses given from the device could change the C-MIC System setting into a safe state and stop the microcurrent.]
  13. Current pregnancy or Breast feeding/lactating women
  14. Women of childbearing potential (WOCBP), defined as all women who are physiologically capable of becoming pregnant, unless they are using a highly effective methods of contraception (failure rate < 1 % per year), as determined by the investigator, for at least 2 months prior to C-MIC therapy and continuing until 1 month after completion of therapy
  15. Patients whose exercise tolerance is limited by a condition other than heart failure (e.g. chronic obstructive pulmonary disease, peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to participate in a 6 minute walk test.
  16. Patients on immunosuppressive therapy.
  17. Patients with present malignancy.
  18. Patients with an active infection considered by the investigator to be unsafe for the patient's participation in the trial.
  19. Patients with renal dysfunction, i.e., estimated glomerular filtration rate (eGFR) <25 mL/min/1.73 m².
  20. Patients with history or presence of relevant liver diseases or hepatic dysfunction as indicated by abnormal liver function tests at screening and baseline: ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase (ALP) and serum bilirubin > 2 × upper limit of normal (ULN). Increase of these liver enzymes caused by cardiac disorders in the absence of other possible causes of liver damage are not meant by this.
  21. Patients with a history of drug or alcohol abuse within the 12 months prior to screening.
  22. Patients who, in the opinion of the Principal Investigator, are unlikely to comply with the protocol requirements, instructions and trial related restrictions, e.g., uncooperative attitude, inability to return for follow-up visits, psychological illness, and improbability of completing the trial.
  23. Participation in any study of an investigational device or drug within 90 days prior to planned study.
  24. Vulnerable Patients (e.g. patients requiring a legal representative, patients kept in detention, any service within the army, and employees of the sponsor or at an investigator site).
  25. Patients who are not able to avoid the following areas (i.e. due to work): a) Areas with strong magnetic fields. b) Areas with strong external electrical influences. c) Areas with a warning notice "Access prohibited for pacemaker patients" or similar. d) Areas with high temperatures Stratum 2 only (ischemic etiology)
  26. Acute coronary event within 3 months prior to screening (def.: unstable angina or STEMI or NSTEMI).
  27. Evidence of significant myocardial scar or left ventricular aneurysm based on imaging (e.g., echocardiography or other modalities), as assessed by the investigator.
  28. Relevant coronary stenosis with indication for re-vascularization (def.: ≥ 50 % stenosis in LMCA, ≥ 70 % stenosis in LAD, RCA, CX.