Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D

Heart Failure NYHA Class III and Ambulatory IV Clinical Trial

— RESPOND-CRT  

Official title:

Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01534234
• Other study ID #: ITSY06 - RESPOND CRT
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: January 2012
• Est. completion date: December 2019

Study information

• Verified date: January 2019
• Source: MicroPort CRM
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess the safety and effectiveness of the automatic atrioventricular (AV) delay and interventricular (VV) delay optimization algorithm used in the PARADYM RF SONR Cardiac Resynchronization Therapy with Defibrillation (CRT-D) device (Model 9770) in combination with the SonRtip Lead, which includes a SonR sensor in the tip of the atrial pacing lead, and compatible SmartView programming software.

This study will evaluate the effectiveness of the automatic optimization algorithm in increasing the rate of patients responding to the therapy as compared to an echocardiographic optimization method.

This study will also evaluate the safety and effectiveness of the SonRtip atrial pacing lead.

Description:

Since the introduction of cardiac resynchronization therapy (CRT) on a large scale, it has been observed that approximately 30% of recipient patients are non-responsive to therapy. This non-responsiveness can be decreased by optimizing the device programming, particularly the stimulation rate, paced and sensed atrioventricular (AV) delay, and the interventricular (VV) delay.

All CRT patients need a 100% rate of ventricular capture, but beyond this the achievement of therapy effectiveness requires the identification of the optimal pacing configuration, which varies among patients. The optimization of CRT systems, usually based on ultrasound imaging is time-consuming and the number of patients in need of multiple optimization procedures due to ventricular remodeling is growing rapidly.

The mechanical effects of a more coordinated contraction result in a shortening of the isovolumetric contraction phase and the pre-ejection time, and an increase in LV dP/dt (change in left ventricular pressure over time. The concept of measuring contractility with an implantable accelerometer was first clinically validated through a multicenter study on a rate responsive pacing system (BEST - Living from SORIN Biomedica) in 1996. This study positively demonstrates that measurement of Peak Endocardial Acceleration signal (called PEA or SonR) is feasible and reliable in the long-term, both for the purpose of rate response and as a hemodynamic monitor of cardiac function.

More recent clinical studies have demonstrated that optimal VV and AV Delays determined using algorithms based on SonR signal analysis (SonR method) are correlated with the highest hemodynamic improvement and lead to significant clinical benefit for the patients, thus reducing the rate of non-responsiveness to CRT therapy.

Therefore, automatic AV and VV delay optimization in patients with CRT devices could benefit both the patient and physician.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1039
• Est. completion date: December 2019
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient eligible with class I and IIa indication for implantation of a CRT-D device according to current available guidelines ;

2. Modere,Severe HF (NYHA Class III or ambulatory IV)

3. LVEF = 35 %

4. LBBB: QRS = 120 ms ; non-LBBB : QRS = 150 ms

5. On a stable, optimal drug regimen

6. Patient is in sinus rhythm at the time of enrollment;

7. Signed and dated informed consent

Exclusion Criteria:

1. Ventricular tachyarrhythmia of transient or reversible causes such as acute myocardial infarction, digitalis intoxication, drowning, electrocution, electrolyte imbalance, hypoxia or sepsis, uncorrected at the time of the enrolment;

2. Incessant ventricular tachyarrhythmia;

3. Unstable angina, or acute MI, CABG, or PTCA within the past 4 weeks;

4. Correctable valvular disease that is the primary cause of heart failure;

5. Recent CVA or TIA (within the previous 3 months);

6. Persistent or permanent atrial arrhythmias (or cardioversion for atrial fibrillation) within the past month;

7. Post heart transplant (patients who are waiting for a heart transplant are allowed in the study);

8. Renal failure (GFR<15 ml/min/1.73m2) or on dialysis

9. Previous implant with a CRT/CRT-D device;

10. Concurrent implant with another pacemaker or ICD (previously implanted pacemaker or ICD devices or RA leads should be removed prior to implant with the Paradym RF SONR CRT-D);

11. Already included in another clinical study that could confound the results of this study;

12. Life expectancy less than 1 year;

13. Inability to understand the purpose of the study or to understand and complete the QOL questionnaire;

14. Unavailability for scheduled follow-up or refusal to cooperate;

15. Sensitivity to 1 mg dexamethasone sodium phosphate (DSP)

16. Age of less than 18 years;

17. Pregnancy

18. Drug addiction or abuse

19. Under guardianship

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure NYHA Class III and Ambulatory IV

Intervention

Device:
• PARADYM RF SONR
SonR CRT Optimization
• PARADYM RF SONR
Echocardiography Optimization

Locations

Country	Name	City	State
Australia	Princess Alexandra Hospital	Brisbane
Australia	Royal Perth Hospital	Perth
Austria	LKH Feldkirch	Feldkirch
Austria	Lkh Innsbruck - Invasoren Kardiologie - Innere Medizin	Innsbruck
Austria	KH Hietzing,4. Medizinische Abteilung Mit Kardiologie	Wien
Austria	SMZ-Ost, 1 Medizinische Abteilung	Wien
Austria	Wilhelminenspital	Wien
France	Hôpital de la Cavale Blanche-CHU BREST	Brest
France	CHU - Hopital Michallon	Grenoble
France	CHRU de Lille,Hôpital Cardiologique	Lille
France	Centre Hospitalier Universitaire de La Timone	Marseille
France	Institut Jacques Cartier	Massy
France	Nouvelles Cliniques Nantaises	Nantes
France	InParys CLINIQUE BIZET	Paris
France	CHU de Bordeaux, Groupe hospitalier Sud, Hôpital Haut-L'évêque	Pessac
France	CH Poitiers	Poitiers
France	CHU Charles Nicolle	Rouen
France	CHU - Hopital Nord	Saint Etienne
France	CH de Rangueil	Toulouse
France	Chru Trousseau	Tours
France	CHU Brabois	Vandoeuvre Les Nancy
France	La Clinique du Tonkin	Villeurbanne
Germany	Herz- und Gefässzentrum Bad Bevensen	Bad Bevensen
Germany	Kerckhoff-Klinik GmbH	Bad Nauheim
Germany	Herz- und Diabeteszentrum Nordrhein-Westfalen	Bad Oeynhausen
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	St.-Marien-Hospital	Bonn
Germany	Universitätskliniken Bonn	Bonn
Germany	Klinikum Coburg	Coburg
Germany	Kardiocentrum Frankfurt and der Klinik Rotes Kreuz	Frankfurt
Germany	Universitäts-Herzzentrum Freiburg	Freiburg
Germany	Albertinen-Krankenhaus	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Schleswig-HolsteinCampus Kiel	Kiel
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Klinikum Magdeburg gemeinnützige GmbH	Magdeburg
Germany	Klinikum Grosshadern	München
Germany	Universitätsklinik Münster Innere Medizin C	Münster
Germany	Krankenhaus Reinbek St. Adolf-Stift	Reinbek
Italy	Ospedale Civile Ss. Antonio E Biago	Alessandria
Italy	Az. Osp-Univ. Ospedali Riuniti Umberto I-Lancisi-Salesi	Ancona
Italy	Azienda Ospedaliera S. Anna e S. Sebastiano	Caserta
Italy	AOU Ferrarotti-Alessi	Catania
Italy	Ospedale Maurizio Bufalini	Cesena
Italy	Azienda Ospedaliera S. Croce E Carle	Cuneo
Italy	Azienda Osped-Universitaria CAREGGI	Firenze
Italy	Casa Di Cura Montevergine	Mercogliano
Italy	Osp. Niguarda	Milan
Italy	Ospedale Civile	Mirano
Italy	SUN Ospedale Monaldi	Napoli
Italy	Fondazione Toscana Gabriele Monasterio	Pisa
Italy	Policlinico Casilino	Roma
Italy	Osp. S. Maria della Misericordia	Rovigo
Italy	IRCCS Multimedica	Sesto San Giovanni
Italy	A.O. Città della Salute e della Scienza di Torino Cardiologia 1 - U	Torino
Italy	A.O. Città della Salute e della Scienza di Torino Cardiologia 2 ospedaliera	Torino
Italy	Ospedale Cà Foncello	Treviso
Italy	Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste	Trieste
Italy	Az. Osp. Univ. S. Maria della Misericordia	Udine
Netherlands	Slingeland Ziekenhuis	Doetinchem
Netherlands	Erasmus MC : University Medical Center	Rotterdam
Netherlands	Vlietland Ziekenhuis	Schiedam
Netherlands	Sint Elisabeth Ziekenhuis	Tilburg
Netherlands	Ziekenhuis Bernhoven	Veghel
Netherlands	ISALA Klinieken	Zwolle
Portugal	Hospital Professor Doutor Fernando Fonseca	Amadora
Portugal	Centro Hospitalar Lisboa Ocidental -Hospital de Santa Cruz (CHLO)	Carnaxide
Portugal	Hospital Santa Maria	Lisboa
Portugal	Centro Hospitalar do Porto CHP Hospital de Santo Antonio	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Slovenia	Klinicni center Ljubljana	Ljubljana
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clinico de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	H. Virgen de las Nieves	Granada
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	H. Universitario Central de Asturias	Oviedo
Spain	Hospital Donostia	San Sebastian
Spain	Hospital Universitario Marques de Valdecilla Sur	Santander
Spain	Hospital Virgen de Valme	Sevilla
Spain	H. General Universit.	Valencia
Spain	CHU VIGO	Vigo
Switzerland	Centre Hospitalier Universitaire Vaudois Lausanne (CHUV)	Lausanne
Switzerland	Fondazione Cardiocentro Ticino	Lugano
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Papworth Everard	Cambridge
United Kingdom	Ashford and St. Peter's Hospitals NHS Trust	Chertsey
United Kingdom	Castle Hill Hospital Hull and East Yorkshire Hospitals NHS T	Cottingham
United Kingdom	Leeds General Infirmary	Leeds
United Kingdom	Genfield General Hospital	Leicester
United Kingdom	King's College Hospital NHS Foundation Trust	London
United States	Piedmont Hospital Research Institute	Atlanta	Georgia
United States	Brookwood Medical Center CardioVascular Associates	Birmingham	Alabama
United States	Massachusetts General Hospital-CAS	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Swedish Covenant Hospital	Chicago	Illinois
United States	The University of Chicago Medicine Hospital	Chicago	Illinois
United States	Good Samaritan Hospital	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals of Cleveland	Cleveland	Ohio
United States	Lexington Cardiology	Columbia	South Carolina
United States	Providence Cardiology d/b/a South Caroline Heart Center	Columbia	South Carolina
United States	Brotman Medical Center	Culver City	California
United States	Baylor Heart & Vascular Hospital	Dallas	Texas
United States	VA North Texas Health Care System	Dallas	Texas
United States	McLeod Regional Medical Center	Florence	South Carolina
United States	Broward General Medical Center	Fort Lauderdale	Florida
United States	Plaza Medical Center of Fort Worth	Fort Worth	Texas
United States	St. Vincent's HealthCare	Jacksonville	Florida
United States	Sparrow Clinical Research Institute	Lansing	Michigan
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	New York Presbyterian	New York	New York
United States	St. Luke's Roosevelt Hospital Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Hoag Hospital	Newport Beach	California
United States	Drexel University College of Medicine	Philadelphia	Pennsylvania
United States	Hospital of the University of PA	Philadelphia	Pennsylvania
United States	AZ Heart Rhythm Center	Phoenix	Arizona
United States	Rochester General Hospital	Rochester	New York
United States	Scripps Mercy Hospital	San Diego	California
United States	St. Francis Hospital	Tulsa	Oklahoma
United States	Forsyth Hospital	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
MicroPort CRM	Sorin CRM

Countries where clinical trial is conducted

United States,  Australia,  Austria,  France,  Germany,  Italy,  Netherlands,  Portugal,  Slovenia,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of SonR CRT Optimization Effectiveness in terms of proportion of responders at 12 months. The investigational(SonR)and control groups(ECHO)will be compared in a non-inferiority context employing a clinically meaningful difference of 10%.	The analysis will be done on all patients implanted with the entire system who have been followed out to 12 months. The patients will be classified as improved, unchanged or worsened based on composite criteria(death/heart failure (HF) events,New York Heart association(NYHA) class), Quality of life (QOL).; In the event that the non-inferiority test is met, a test of superiority will be conducted comparing the treatment and control groups.	12 months
Primary	Evaluation of Lead Safety: Acute SonRTipLead Complication-Free Rate (at 3 months)	SonRtip acute lead-related complication-free rate is defined as the proportion of patients not experiencing any complication related to the SonRtip lead within 3 months post-implant, relative to the total number of patients implanted with the lead.All patients who are successfully implanted with SonRtip lead will be included.	3 months
Primary	Evaluation of Lead Safety: Chronic SonRTipLead Complication-Free Rate (from 3 months to 12 months)	SonRtip lead-related complication-free rate is defined as the proportion of patients not experiencing any complication related to the SonRtip lead from 3 to 12 months post-implant.All patients who are successfully implanted with SonRtip lead will be included.	12 months
Secondary	Evaluation of CRT effectiveness and CRT Safety: evaluation of Mortality and HF hospitalizations at 12 months	This endpoint will compare treatment arms in a non-inferiority hypothesis test of the proportion of subjects that either died from any cause, or were hospitalized for heart failure	12 months
Secondary	Evaluation of CRT effectiveness and CRT therapy: Proportion of patients worsened at 12 months	This endpoint will compare treatment arms in a non-inferiority hypothesis test of the proportion of subjects classified as worsened, in order to evaluate the potential detrimental effects of the optimization method	12 months
Secondary	SonR tip lead pacing threshold	For all patients implanted with the SonRtip lead.	24 months
Secondary	SonR tip lead sensing threshold	For all patients implanted with the SonRtip lead.	24 months
Secondary	SonR tip lead pacing impedance	For all patients implanted with the SonRtip lead.	24 months
Secondary	Evaluation of CRT effectiveness and CRT and System Safety: Report deaths for any cause	The report of the deaths occurred consists of the percentage of dead patients, the causes of death, the time to death, the survival curves.	24 months
Secondary	Report Heart Failure-related events to assess CRT effectiveness	For all patients implanted it will be reported the percentage of patients with events, number of events for patients, event type, time to first occurence, survival curves)	24 months
Secondary	Report Quality of life (QOL) improvement to assess CRT effectiveness (percentage of patients with improvements in QOL)	In all patients implanted the evaluation of the Quality of Life Score will consist of reporting the percentage of patients who showed improvement in their KCCQ Score at each follow-up post-implant	24 months
Secondary	Report NYHA class improvement to assess CRT effectiveness (the percentage of patients with improved in NYHA class)	In all patients implanted the evaluation of the NYHA Classification will consist of reporting the percentage of patients who improved at least one NYHA class at each follow-up post-implant	24 months
Secondary	Evaluation of CRT effectiveness: Report echocardiographic parameters trend at M12	The intra-patient variations of the echocardiographic parameters measured at M12 as compared to those measured at baseline. The echo measures will be validated by an independent and blinded core lab	12 months
Secondary	Evaluation of SonR CRT Optimization Effectiveness - Superiority by assessment the proportion of responder patients in SonR group	The analysis will be done on all patients implanted with the entire system. The patients will be classified as improved, unchanged or worsened based on composite criteria(death/heart failure events,NYHA class, Quality of life (QOL).	18/24 months
Secondary	Evaluation of the time spent for CRT optimization by the physician on optimization in each group (sonR and ECHO)	The amount of time (mean, median, standard deviation, minimum, maximum)in each group will be evaluated in all patients implanted	24 months
Secondary	Evaluation of the Number of re-optimizations performed in both groups (SonR and ECHO)	In all patients implanted will be evaluated the number of re-optimizations performed (mean, median, standard deviation, minimum, maximum) in each group (study and control).	24 months
Secondary	Report Adverse Events for both group to assess CRT effectiveness / System Safety	For all patients enrolled all Adverse Events will be reported.	24 months