CCM in Heart Failure With Preserved Ejection Fraction (CCM-HFpEF)

Cardiac Contractility Modulation Therapy in Subjects With Heart Failure With Preserved Ejection Fraction

This pilot study will evaluate the efficacy and safety of CCM therapy in heart failure patients with baseline EF≥50% (HFpEF) who have New York Heart Association (NYHA) Class II or III symptoms despite appropriate medication.

The terminology of the HF classification HFpEF is based on the 2016 European Society of Cardiology (ESC) Heart Failure Guidelines.

Study Overview

• Status: Completed
• Conditions: Heart Failure, Diastolic
• Intervention / Treatment: Device: Optimizer SMART

Detailed Description

This is a pilot clinical study of CCM in addition to optimal medical therapy (OMT) over a 24 week period.The primary endpoint shall be mean change from baseline to 24 weeks in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score (reflecting integrated information on physical limitations, symptoms, self-efficacy, social interference and quality of life).

This pilot study will collect efficacy and safety data in heart failure patients having NYHA class II and III symptoms despite appropriate medication with baseline ejection fraction equal or greater than 50% (HFpEF populations).

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Bunbury, Australia, 6150
    • St. John of God Bunbury
  • Perth, Australia, 6000
    • St. John of God Murdoch Hospital
  • Queensland
    • Bundaberg, Queensland, Australia, 4670
      • Friendly Society Private Hospital
• Czechia
  • Praha 5, Czechia, 15030
    • Hospital Na Homolce
• Germany
  • Hesse
    • Bad Nauheim, Hesse, Germany, 61231
      • Kerckhoff-Klinik GmbH
• Italy
  • Milan, Italy
    • Auxologico Institute
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Rome
    • Ancona, Rome, Italy
      • INRCA IRCCS Ancona
• Poland
  • Warsaw, Poland, 02-097
    • Uniwersyteckie Centrum Kliniczne Warszawskiego Uniwersytetu Medycznego zakład leczniczy Centralnego Szpitala Klinicznego
  • Wroclaw, Poland, 50-981
    • 4 Wojskowy Szpital Kliniczny z Poliklinika SPZOZ we Wroclawiu
  • Wrocław, Poland, 50-556
    • Uniwersytecki Szpital Kliniczny we Wrocław
• Portugal
  • Lisbon, Portugal
    • West Lisbon Hospital Center, E.P.E., hereinafter referred to as CHLO, E.P.E
• Spain
  • Alicante, Spain, 3010
    • Hospital General de Alicante
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre Unidad de Insuficiencia Cardiaca y Trasplante Servicio de Cardiología, Planta 6. Bloque D.Ciber 8
  • Vigo, Spain, 36312
    • Hospital Alvaro Cunquero
  • C/ A Choupana S.n
    • Santiago De Compostela, C/ A Choupana S.n, Spain, 15706
      • Santiago de Compostella -- Servicio de Cardiología y UCC/ Cardiology and Coronary Care Department Hospital Clínico Universitario. XXI de Santiago de Compostela SERGAS
• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

1. Inclusion criteria

   1. Baseline ejection fraction ≥ 50% (as assessed by echocardiogram within 30 days of enrollment and confirmed by the echo core laboratory).
   2. NYHA class II or III symptoms despite receiving stable optimal medical therapy (OMT) for at least 30 days based on patient's medical records (chronic stable, not transient or crescendo heart failure or angina pectoris)
   3. Stable optimal medical therapy for Heart failure for 3 months.
   4. NT-proBNP > 220 pg/ml for subjects in sinus rhythm or > 600 pg/ml for subjects in atrial fibrillation

   5. Has the following (as assessed by the core lab):

      • LAVi ≥ 34 ml/m² or LVH >12mm AND either
      • E/e' ≥ 13 OR
      • septal e' < 7 cm/s or lateral e' <10 cm/s
   6. Patient giving informed consent, willing to be available for scheduled study follow-up visits, and able to complete all testing of the study protocol

2. Exclusion criteria

   1. Age below 40 or greater than 80
   2. Patients with expected lifespan of less than 12 months from time of enrollment
   3. Subjects referred to an institution based on a judicial or administrative order
   4. Dilated left ventricle, as evidenced by LVEDVI >= 97 mL/m2 (as assessed by the echo core lab)
   5. Primary cardiac valvular disease (anything more than grade 2)
   6. Congenital or untreated ischemic heart disease
   7. Infiltrative / inflammatory / genetic cardiomyopathy as documented in the medical record (e.g. amyloid, hemochromatosis, myocarditis, hypertrophic cardiomyopathy, M. Fabry, cardiac tumor), or persistent large pericardial effusion
   8. Unstable or frequent (>1 episode/week) angina pectoris
   9. Hospitalization for HF requiring the use of inotropic support or IABP within 30 days of enrollment
   10. Systolic Blood Pressure > 160 mmHg
   11. Uncorrected severe anemia (e.g. hemoglobin <9g/dL)
   12. PR interval greater than 375 ms
   13. Exercise tolerance limited due to noncardiac disorders (e.g. deconditioning, severe lung disease, frailty)
   14. Scheduled for a cardiac surgery or a PCI procedure, or had a cardiac surgery procedure within 90 days or a PCI procedure within 30 days prior to enrollment
   15. Myocardial infarction within 90 days of enrollment
   16. Cardioversion within 30 days of enrollment
   17. History of significant ectopy either on 12-lead ECG or Holter monitoring (more than 10% PVCs).
   18. Heart rate > 110 bpm on ECG for patients with atrial fibrillation
   19. Mechanical tricuspid valve
   20. Prior heart transplant or ventricular assist device
   21. Pregnant or planning to become pregnant during the study
   22. Breastfeeding subjects
   23. Subject participating in another medical therapy or device related study, unrelated to CCM™, at the same time or within 30 days prior to enrollment into this study
   24. Subjects on dialysis, or with documented GFR<30 or with other major medical disorder (e.g. severe anemia, liver failure)
   25. Subjects with any active non-cardiac implants

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CCM therapy; Optimizer SMART	Device: Optimizer SMART; Cardiac Contractility Modulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
KCCQ change	Mean change from baseline to 24 weeks in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Echocardiography	LAVi and diastolic function: septal E' velocity, septal E/E' ratio	24 weeks
NT-proBNP	Mean Change in 24 weeks	24 weeks
NYHA class	Mean Change in 24 weeks	24 weeks

Collaborators and Investigators

• Sponsor: Impulse Dynamics
• Investigators: Principal Investigator: Carsten Tschoepe, Prof., University Hospital Charite Berlin

Publications and helpful links

General Publications

• Tschope 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. No abstract available.
• Linde C, Grabowski M, Ponikowski P, Rao I, Stagg A, Tschope C. Cardiac contractility modulation therapy improves health status in patients with heart failure with preserved ejection fraction: a pilot study (CCM-HFpEF). Eur J Heart Fail. 2022 Dec;24(12):2275-2284. doi: 10.1002/ejhf.2619. Epub 2022 Aug 11.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2018
• Primary Completion (Actual): July 25, 2023
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: August 2, 2017
• First Submitted That Met QC Criteria: August 2, 2017
• First Posted (Actual): August 7, 2017

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: HFpEF
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Heart Failure, Diastolic
• Other Study ID Numbers: ID_CP_OPT2016-012_0

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No