Clinical trial NCT01534234: Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D
Official title: Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Heart Failure NYHA Class III and Ambulatory IV
Keywords: CRT-D device
Severe HF (NYHA Class III or ambulatory IV)
stable, optimal drug regimen
sinus rhythm
Lead sponsor: MicroPort CRM
Sponsor class: INDUSTRY
Collaborators: name: Sorin CRM
First posted: 2012-02-16
Enrollment: 1039
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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%.
timeFrame: 12 months
measure: Evaluation of Lead Safety: Acute SonRTipLead Complication-Free Rate (at 3 months)
timeFrame: 3 months
measure: Evaluation of Lead Safety: Chronic SonRTipLead Complication-Free Rate (from 3 months to 12 months)
timeFrame: 12 months
Secondary outcomes:
measure: Evaluation of CRT effectiveness and CRT Safety: evaluation of Mortality and HF hospitalizations at 12 months
timeFrame: 12 months
measure: Evaluation of CRT effectiveness and CRT therapy: Proportion of patients worsened at 12 months
timeFrame: 12 months
measure: SonR tip lead pacing threshold
timeFrame: 24 months
measure: SonR tip lead sensing threshold
timeFrame: 24 months
measure: SonR tip lead pacing impedance
timeFrame: 24 months
measure: Evaluation of CRT effectiveness and CRT and System Safety: Report deaths for any cause
timeFrame: 24 months
measure: Report Heart Failure-related events to assess CRT effectiveness
timeFrame: 24 months
measure: Report Quality of life (QOL) improvement to assess CRT effectiveness (percentage of patients with improvements in QOL)
timeFrame: 24 months
measure: Report NYHA class improvement to assess CRT effectiveness (the percentage of patients with improved in NYHA class)
timeFrame: 24 months
measure: Evaluation of CRT effectiveness: Report echocardiographic parameters trend at M12
timeFrame: 12 months
measure: Evaluation of SonR CRT Optimization Effectiveness - Superiority by assessment the proportion of responder patients in SonR group
timeFrame: 18/24 months
measure: Evaluation of the time spent for CRT optimization by the physician on optimization in each group (sonR and ECHO)
timeFrame: 24 months
measure: Evaluation of the Number of re-optimizations performed in both groups (SonR and ECHO)
timeFrame: 24 months
measure: Report Adverse Events for both group to assess CRT effectiveness / System Safety
timeFrame: 24 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Brookwood Medical Center CardioVascular Associates
state: Alabama
city: Phoenix
country: United States
facility: AZ Heart Rhythm Center
state: Arizona
city: Culver City
country: United States
facility: Brotman Medical Center
state: California
city: Newport Beach
country: United States
facility: Hoag Hospital
state: California
city: San Diego
country: United States
facility: Scripps Mercy Hospital
state: California
city: Fort Lauderdale
country: United States
facility: Broward General Medical Center
state: Florida
city: Jacksonville
country: United States
facility: St. Vincent's HealthCare
state: Florida
city: Atlanta
country: United States
facility: Piedmont Hospital Research Institute
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: Swedish Covenant Hospital
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medicine Hospital
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital-CAS
state: Massachusetts
city: Lansing
country: United States
facility: Sparrow Clinical Research Institute
state: Michigan
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: New York
country: United States
facility: St. Luke's Roosevelt Hospital Center
state: New York
city: New York
country: United States
facility: New York Presbyterian
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Winston-Salem
country: United States
facility: Forsyth Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Tulsa
country: United States
facility: St. Francis Hospital
state: Oklahoma
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of PA
state: Pennsylvania
city: Columbia
country: United States
facility: Lexington Cardiology
state: South Carolina
city: Columbia
country: United States
facility: Providence Cardiology d/b/a South Caroline Heart Center
state: South Carolina
city: Florence
country: United States
facility: McLeod Regional Medical Center
state: South Carolina
city: Dallas
country: United States
facility: VA North Texas Health Care System
state: Texas
city: Dallas
country: United States
facility: Baylor Heart & Vascular Hospital
state: Texas
city: Fort Worth
country: United States
facility: Plaza Medical Center of Fort Worth
state: Texas
city: Brisbane
country: Australia
facility: Princess Alexandra Hospital
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Feldkirch
country: Austria
facility: LKH Feldkirch
city: Innsbruck
country: Austria
facility: Lkh Innsbruck - Invasoren Kardiologie - Innere Medizin
city: Wien
country: Austria
facility: KH Hietzing,4. Medizinische Abteilung Mit Kardiologie
city: Wien
country: Austria
facility: Wilhelminenspital
city: Wien
country: Austria
facility: SMZ-Ost, 1 Medizinische Abteilung
city: Brest
country: France
facility: Hôpital de la Cavale Blanche-CHU BREST
city: Grenoble
country: France
facility: CHU - Hopital Michallon
city: Lille
country: France
facility: CHRU de Lille,Hôpital Cardiologique
city: Marseille
country: France
facility: Centre Hospitalier Universitaire de La Timone
city: Massy
country: France
facility: Institut Jacques Cartier
city: Nantes
country: France
facility: Nouvelles Cliniques Nantaises
city: Paris
country: France
facility: InParys CLINIQUE BIZET
city: Pessac
country: France
facility: CHU de Bordeaux, Groupe hospitalier Sud, Hôpital Haut-L'évêque
city: Poitiers
country: France
facility: CH Poitiers
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Saint Etienne
country: France
facility: CHU - Hopital Nord
city: Toulouse
country: France
facility: CH de Rangueil
city: Tours
country: France
facility: Chru Trousseau
city: Vandoeuvre Les Nancy
country: France
facility: CHU Brabois
city: Villeurbanne
country: France
facility: La Clinique du Tonkin
city: Bad Bevensen
country: Germany
facility: Herz- und Gefässzentrum Bad Bevensen
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik GmbH
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Bonn
country: Germany
facility: St.-Marien-Hospital
city: Bonn
country: Germany
facility: Universitätskliniken Bonn
city: Coburg
country: Germany
facility: Klinikum Coburg
city: Frankfurt
country: Germany
facility: Kardiocentrum Frankfurt and der Klinik Rotes Kreuz
city: Freiburg
country: Germany
facility: Universitäts-Herzzentrum Freiburg
city: Hamburg
country: Germany
facility: Albertinen-Krankenhaus
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-HolsteinCampus Kiel
city: Ludwigshafen
country: Germany
facility: Klinikum Ludwigshafen
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg gemeinnützige GmbH
city: München
country: Germany
facility: Klinikum Grosshadern
city: Münster
country: Germany
facility: Universitätsklinik Münster Innere Medizin C
city: Reinbek
country: Germany
facility: Krankenhaus Reinbek St. Adolf-Stift
city: Alessandria
country: Italy
facility: Ospedale Civile Ss. Antonio E Biago
city: Ancona
country: Italy
facility: Az. Osp-Univ. Ospedali Riuniti Umberto I-Lancisi-Salesi
city: Caserta
country: Italy
facility: Azienda Ospedaliera S. Anna e S. Sebastiano
city: Catania
country: Italy
facility: AOU Ferrarotti-Alessi
city: Cesena
country: Italy
facility: Ospedale Maurizio Bufalini
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce E Carle
city: Firenze
country: Italy
facility: Azienda Osped-Universitaria CAREGGI
city: Mercogliano
country: Italy
facility: Casa Di Cura Montevergine
city: Milan
country: Italy
facility: Osp. Niguarda
city: Mirano
country: Italy
facility: Ospedale Civile
city: Napoli
country: Italy
facility: SUN Ospedale Monaldi
city: Pisa
country: Italy
facility: Fondazione Toscana Gabriele Monasterio
city: Roma
country: Italy
facility: Policlinico Casilino
city: Rovigo
country: Italy
facility: Osp. S. Maria della Misericordia
city: Sesto San Giovanni
country: Italy
facility: IRCCS Multimedica
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza di Torino Cardiologia 1 - U
city: Torino
country: Italy
facility: A.O. Città della Salute e della Scienza di Torino Cardiologia 2 ospedaliera
city: Treviso
country: Italy
facility: Ospedale Cà Foncello
city: Trieste
country: Italy
facility: Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste
city: Udine
country: Italy
facility: Az. Osp. Univ. S. Maria della Misericordia
city: Doetinchem
country: Netherlands
facility: Slingeland Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC : University Medical Center
city: Schiedam
country: Netherlands
facility: Vlietland Ziekenhuis
city: Tilburg
country: Netherlands
facility: Sint Elisabeth Ziekenhuis
city: Veghel
country: Netherlands
facility: Ziekenhuis Bernhoven
city: Zwolle
country: Netherlands
facility: ISALA Klinieken
city: Amadora
country: Portugal
facility: Hospital Professor Doutor Fernando Fonseca
city: Carnaxide
country: Portugal
facility: Centro Hospitalar Lisboa Ocidental -Hospital de Santa Cruz (CHLO)
city: Lisboa
country: Portugal
facility: Hospital Santa Maria
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto CHP Hospital de Santo Antonio
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Ljubljana
country: Slovenia
facility: Klinični center Ljubljana
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Clinico de Barcelona
city: Granada
country: Spain
facility: H. Virgen de las Nieves
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Majadahonda
country: Spain
facility: Hospital Puerta de Hierro
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Oviedo
country: Spain
facility: H. Universitario Central de Asturias
city: San Sebastian
country: Spain
facility: Hospital Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla Sur
city: Sevilla
country: Spain
facility: Hospital Virgen de Valme
city: Valencia
country: Spain
facility: H. General Universit.
city: Vigo
country: Spain
facility: CHU VIGO
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne (CHUV)
city: Lugano
country: Switzerland
facility: Fondazione Cardiocentro Ticino
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cambridge
country: United Kingdom
facility: Papworth Everard
city: Chertsey
country: United Kingdom
facility: Ashford and St. Peter's Hospitals NHS Trust
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital Hull and East Yorkshire Hospitals NHS T
city: Leeds
country: United Kingdom
facility: Leeds General Infirmary
city: Leicester
country: United Kingdom
facility: Genfield General Hospital
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Josep Brugada
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brugada J, Delnoy PP, Brachmann J, Reynolds D, Padeletti L, Noelker G, Kantipudi C, Rubin Lopez JM, Dichtl W, Borri-Brunetto A, Verhees L, Ritter P, Singh JP; RESPOND CRT Investigators. Contractility sensor-guided optimization of cardiac resynchronization therapy: results from the RESPOND-CRT trial. Eur Heart J. 2017 Mar 7;38(10):730-738. doi: 10.1093/eurheartj/ehw526.
citation: Brugada J, Brachmann J, Delnoy PP, Padeletti L, Reynolds D, Ritter P, Borri-Brunetto A, Singh JP. Automatic optimization of cardiac resynchronization therapy using SonR-rationale and design of the clinical trial of the SonRtip lead and automatic AV-VV optimization algorithm in the paradym RF SonR CRT-D (RESPOND CRT) trial. Am Heart J. 2014 Apr;167(4):429-36. doi: 10.1016/j.ahj.2013.12.007. Epub 2013 Dec 19.