CCM Italian Registry

NCT04327323 | Unknown

• 1 other identifier: CCM-REG-IT
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The Cardiac Contractility Modulation (CCM) system is a cardiac implantable device indicated for the treatment of patients with symptomatic heart failure with left ventricular systolic dysfunction despite optimal medical and electrical therapy. This system consists of a generator to which two stimulation leads are connected, which are fixed on the interventricular septum and deliver non-excitatory electrical signals during the absolute ventricular refractory period, with the aim of influencing the contractility properties of the myocardium in patients with chronic heart failure. Clinical data indicate that CCM therapy is safe and effective for the treatment of patients with symptomatic heart failure with reduced left ventricular systolic function, in which a significant improvement in quality of life and exercise tolerance has been shown, together with an impact on hospitalizations for heart failure. This prospective registry includes patients undergoing CCM implantation for the above clinical indications. The inclusion criteria are age over 18; chronic heart failure with reduced left ventricular systolic function (FE ≤ 45%), symptomatic (class NYHA II or greater; class III or greater or II with episodes of acute decompensation for patients with FE 36-45%); presence of appropriate and optimized medical therapy (including beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers or angiotensin-receptor neprylysin inhibitors and anti-aldosterone agents); narrow QRS (\<120 msec) or cardiac resynchronization therapy non-responders; written informed consent for enrollment and participation in the prospective register; life expectancy\> 1 year due to the absence of non-cardiac comorbidities that reduce its prognosis; availability of venous access that can be used for the implant. The exclusion criteria are the absence of venous access available for the implant; contraindication to the interventional CCM implant procedure; life expectancy of less than one year due to non-cardiovascular comorbidities. The aim of this multicenter, prospective, observational registry is to investigate the impact of CCM on the medium and long-term on clinical and functional characteristics of the enrolled patients at the end of the follow-up, with respect to the baseline value: NYHA class, 6-minute walk test, ejection fraction and volumes of the left ventricle, quality of life expressed through a specific questionnaire (Minnesota Living With Heart Failure Questionnaire, MLWHF), hospitalizations for heart failure or progression of the underlying heart disease. In addition, the survival of patients undergoing CCM device implantation will be assessed in an observational manner at 24 months and then annually. In addition, adverse events related to the device implantation procedure or to CCM therapy are collected in the registry as a safety parameter. In the case of patients undergoing heart transplantation or LVAD implantation, or in the event of interruption of therapy or explantation of a device, the information will be recorded with the motivation for discontinuing treatment. Clinical follow-up includes follow-up assessments at 3 months, 6 months, 12 months and every 6 months thereafter. Each clinical follow-up visit includes objective examination, ECG, device function check, administration of an MLWHF quality of life questionnaire, a 6-minute walk test (or cardiopulmonary exercise test) and pharmacological therapy assessment and optimization. Furthermore, during the follow-up visits at 3 months, 12 months and every 12 months thereafter, a transthoracic echocardiogram and blood chemistry tests are scheduled. This multicenter observational prospective registry therefore aims to assess the long-term clinical impact of CCM in patients suffering from symptomatic heart failure with moderately or severely impaired systolic function. In particular, it will allow to evaluate the impact on functional capacity, symptoms and quality of life, hospitalizations, survival and device-related complications, with the aim of defining the role of CCM therapy in management of patient with heart failure with reduced left ventricular systolic function.

Conditions

Heart Failure

Keywords

cardiac contractility modulation; heart failure; hospitalizations; exercise tolerance

Outcome Measures

Primary Outcomes (3)

• Exercise tolerance

  6-minute walking test distance (meters)

  24 months

• Quality of life measured by Minnesota Living With Heart Failure questionnaire

  Minnesota Living With Heart Failure questionnaire score (scale 0-105; high scorse mean worse outcome)

  24 months

• Functional class

  NYHA (New York Heart Association) class (range I-IV; IV means worse outcome)

  24 months

Secondary Outcomes (3)

• Left ventricular systolic function

  24 months

• Hospitalizations

  24 months

• Left ventricular volume

  24 months

Other Outcomes (3)

• Survival

  24 months

• Complications

  24 months

• Others

  24 months

Interventions

CCM device implantation DEVICE

CCM implantation involves the introduction of two active fixation stimulation leads, fixed on the interventricular septum, and connected to the CCM generator (Optimizer Smart IV, Impulse Dynamic, and any subsequent versions of the same device) inserted in the subcutaneous or submuscular pocket. The implantation is ususally performed using vascular access via right or left cephalic or subclavian vein. The CCM signal consists of 2-3 biphasic pulses lasting 10 msec (total duration of about 20 ms) with an amplitude between 4.0 and 7.5 V, delivered during the absolute refractory period of the ventricle, at a distance of 40 msec from ventricular sensing. The CCM device is compatible with other pacing and defibrillation devices already implanted in the patient; at the time of the implantation, the devices are checked in order to confirm the absence of interference between the devices. The patient is instructed to charge the device battery weekly.

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This prospective registry includes patients undergoing CCM implantation for the presence of symptomatic heart failure with moderately-to-severely reduced left ventricular systolic function despite optimal pharmacological and electrical therapy. The clinical trial study (prospective registry) will be conducted in accordance with this protocol, with the Helsinki Declaration and with the favorable opinion of the local Ethics Committee of the participating Centers.

You may qualify if:

• chronic heart failure with reduced left ventricular systolic function (EF ≤ 45%), symptomatic (class NYHA III or greater; or class II with previous episodes of acute decompensation for patients with FE 36-45%);
• presence of appropriate and optimized medical therapy, including: beta-blocker and angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker or angiotensin-receptor neprylysin inhibitor and anti-aldosterone agent, titrated as tolerated by the patients;
• narrow QRS (\<120 msec) or cardiac resynchronization carriers with documented non-response to this treatment;
• age above 18 years;
• written informed consent for enrollment and participation in the prospective register.

You may not qualify if:

• life expectancy \< 1 year due to non-cardiac comorbidities that reduce the prognosis;
• absence of vascular access that can be used for the implant;
• other contraindications to the CCM implantation procedure (e.g. active infective processes, active severe coagulopathies);
• refusal to be enrolled in the registry.

Sponsors & Collaborators

• S. Andrea Hospital: lead
• Ospedale Umberto I di Torino: collaborator
• A.O.U. Città della Salute e della Scienza - Molinette Hospital: collaborator
• Ospedale Cardinal Massaia: collaborator
• Azienda Ospedaliero Universitaria Maggiore della Carita: collaborator
• Azienda Ospedaliera S. Maria della Misericordia: collaborator
• IRCCS Multimedica: collaborator
• San Giovanni di Dio Hospital: collaborator
• Monaldi Hospital: collaborator
• Ospedale Miulli, Acquaviva delle Fonti: collaborator
• Ospedale San Bortolo di Vicenza: collaborator
• The Mediterranean Institute for Transplantation and Advanced Specialized Therapies: collaborator
• ASST Fatebenefratelli Sacco: collaborator
• Ospedale Policlinico San Martino: collaborator
• Azienda Ospedaliera Bolognini di Seriate Bergamo: collaborator
• Federico II University: collaborator
• Ospedale Santa Croce-Carle Cuneo: collaborator
• Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria: collaborator
• Martini Hospital, Turin, Italy: collaborator
• Ospedale di Ariano Irpino: collaborator
• Ospedale di Borgomanero: collaborator
• ASL Verbano Cusio Ossola: collaborator
• Policlinico Hospital: collaborator
• Azienda Ospedaliero Universitaria di Cagliari: collaborator
• Fatebenefratelli Hospital: collaborator
• Centro Cuore Morgagni, Pedara: collaborator
• Santa Maria delle Grazie Hospital: collaborator
• Ospedale di Gorizia: collaborator
• ASP Enna: collaborator
• Ospedale Garibaldi, Catania: collaborator
• Ospedali Riuniti Anzio-Nettuno: collaborator
• Ospedale Fracastoro, Soave San Bonifacio: collaborator
• Ospedale Magalini, Villafranca: collaborator
• Casa di Cura Pierangeli, Pescara: collaborator

Study Sites (1)

Sant'Andrea Hospital

Vercelli, VC, 13100, Italy

RECRUITING

Related Publications (8)

• Borggrefe MM, Lawo T, Butter C, Schmidinger H, Lunati M, Pieske B, Misier AR, Curnis A, Bocker D, Remppis A, Kautzner J, Stuhlinger M, Leclerq C, Taborsky M, Frigerio M, Parides M, Burkhoff D, Hindricks G. Randomized, double blind study of non-excitatory, cardiac contractility modulation electrical impulses for symptomatic heart failure. Eur Heart J. 2008 Apr;29(8):1019-28. doi: 10.1093/eurheartj/ehn020. Epub 2008 Feb 12.

  PMID: 18270213 BACKGROUND

• Kuck KH, Bordachar P, Borggrefe M, Boriani G, Burri H, Leyva F, Schauerte P, Theuns D, Thibault B; Document Reviewers; Kirchhof P, Hasenfuss G, Dickstein K, Leclercq C, Linde C, Tavazzi L, Ruschitzka F. New devices in heart failure: an European Heart Rhythm Association report: developed by the European Heart Rhythm Association; endorsed by the Heart Failure Association. Europace. 2014 Jan;16(1):109-28. doi: 10.1093/europace/eut311. Epub 2013 Nov 20.

  PMID: 24265466 BACKGROUND

• Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf.2018.04.010. Epub 2018 May 10.

  PMID: 29754812 BACKGROUND

• Kloppe A, Lawo T, Mijic D, Schiedat F, Muegge A, Lemke B. Long-term survival with Cardiac Contractility Modulation in patients with NYHA II or III symptoms and normal QRS duration. Int J Cardiol. 2016 Apr 15;209:291-5. doi: 10.1016/j.ijcard.2016.02.001. Epub 2016 Feb 3.

  PMID: 26908357 BACKGROUND

• Kuschyk J, Roeger S, Schneider R, Streitner F, Stach K, Rudic B, Weiss C, Schimpf R, Papavasilliu T, Rousso B, Burkhoff D, Borggrefe M. Efficacy and survival in patients with cardiac contractility modulation: long-term single center experience in 81 patients. Int J Cardiol. 2015 Mar 15;183:76-81. doi: 10.1016/j.ijcard.2014.12.178. Epub 2015 Jan 20.

  PMID: 25662055 BACKGROUND

• Butter C, Rastogi S, Minden HH, Meyhofer J, Burkhoff D, Sabbah HN. Cardiac contractility modulation electrical signals improve myocardial gene expression in patients with heart failure. J Am Coll Cardiol. 2008 May 6;51(18):1784-9. doi: 10.1016/j.jacc.2008.01.036.

  PMID: 18452785 BACKGROUND

• Imai M, Rastogi S, Gupta RC, Mishra S, Sharov VG, Stanley WC, Mika Y, Rousso B, Burkhoff D, Ben-Haim S, Sabbah HN. Therapy with cardiac contractility modulation electrical signals improves left ventricular function and remodeling in dogs with chronic heart failure. J Am Coll Cardiol. 2007 May 29;49(21):2120-8. doi: 10.1016/j.jacc.2006.10.082. Epub 2007 May 17.

  PMID: 17531662 BACKGROUND

• Anker SD, Borggrefe M, Neuser H, Ohlow MA, Roger S, Goette A, Remppis BA, Kuck KH, Najarian KB, Gutterman DD, Rousso B, Burkhoff D, Hasenfuss G. Cardiac contractility modulation improves long-term survival and hospitalizations in heart failure with reduced ejection fraction. Eur J Heart Fail. 2019 Sep;21(9):1103-1113. doi: 10.1002/ejhf.1374. Epub 2019 Jan 16.

  PMID: 30652394 BACKGROUND

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 31, 2020
• Study Start: September 1, 2019
• Primary Completion: September 1, 2021
• Study Completion: September 1, 2023
• Last Updated: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)