CCM in Heart Failure With Preserved Ejection Fraction

Heart Failure, Diastolic Clinical Trial

— CCM-HFpEF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03240237
• Other study ID #: ID_CP_OPT2016-012_0
• Status: Completed
• Phase: N/A
• Start date: May 1, 2018
• Est. completion date: July 25, 2023

Study information

• Verified date: April 2024
• Source: Impulse Dynamics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: July 25, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Diastolic

Intervention

Device:
• Optimizer SMART
Cardiac Contractility Modulation

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Impulse Dynamics

Countries where clinical trial is conducted

Australia,  Czechia,  Germany,  Italy,  Poland,  Portugal,  Spain,  Sweden, 

References & Publications (2)

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):22 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	KCCQ change	Mean change from baseline to 24 weeks in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall score	24 weeks
Secondary	Echocardiography	LAVi and diastolic function: septal E' velocity, septal E/E' ratio	24 weeks
Secondary	NT-proBNP	Mean Change in 24 weeks	24 weeks
Secondary	NYHA class	Mean Change in 24 weeks	24 weeks