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

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.

Study Overview

• Status: Unknown
• Conditions: Heart Failure NYHA Class III and Ambulatory IV
• Intervention / Treatment: Device: PARADYM RF SONR; Device: PARADYM RF SONR

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.

• Study Type: Interventional
• Enrollment (Actual): 1039
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4104
    • Princess Alexandra Hospital
  • Perth, Australia, 6000
    • Royal Perth Hospital
• Austria
  • Feldkirch, Austria, 6807
    • LKH Feldkirch
  • Innsbruck, Austria, 6020
    • Lkh Innsbruck - Invasoren Kardiologie - Innere Medizin
  • Wien, Austria, 1160
    • Wilhelminenspital
  • Wien, Austria, 1130
    • KH Hietzing,4. Medizinische Abteilung Mit Kardiologie
  • Wien, Austria, 1220
    • SMZ-Ost, 1 Medizinische Abteilung
• France
  • Brest, France, 29609
    • Hôpital de la Cavale Blanche-CHU BREST
  • Grenoble, France, 38043
    • CHU - Hopital Michallon
  • Lille, France, 59037
    • CHRU de Lille,Hôpital Cardiologique
  • Marseille, France, 13000
    • Centre Hospitalier Universitaire de La Timone
  • Massy, France, 91300
    • Institut Jacques Cartier
  • Nantes, France, 44277
    • Nouvelles Cliniques Nantaises
  • Paris, France, 75016
    • InParys CLINIQUE BIZET
  • Pessac, France, 33604
    • CHU de Bordeaux, Groupe hospitalier Sud, Hôpital Haut-L'évêque
  • Poitiers, France
    • CH Poitiers
  • Rouen, France
    • CHU Charles Nicolle
  • Saint Etienne, France, 42055
    • Chu - Hopital Nord
  • Toulouse, France, 31059
    • CH de Rangueil
  • Tours, France, 37044
    • CHRU Trousseau
  • Vandoeuvre Les Nancy, France, 54500
    • CHU Brabois
  • Villeurbanne, France, 69626
    • La Clinique du Tonkin
• Germany
  • Bad Bevensen, Germany, 29549
    • Herz- und Gefasszentrum Bad Bevensen
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik GmbH
  • Bad Oeynhausen, Germany, 32545
    • Herz- und Diabeteszentrum Nordrhein-Westfalen
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin
  • Bonn, Germany
    • Universitatskliniken Bonn
  • Bonn, Germany, 53115
    • St.-Marien-Hospital
  • Coburg, Germany, 96450
    • Klinikum Coburg
  • Frankfurt, Germany, 60316
    • Kardiocentrum Frankfurt and der Klinik Rotes Kreuz
  • Freiburg, Germany, 79106
    • Universitäts-Herzzentrum Freiburg
  • Hamburg, Germany, 22457
    • Albertinen-Krankenhaus
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-HolsteinCampus Kiel
  • Ludwigshafen, Germany, 67063
    • Klinikum Ludwigshafen
  • Magdeburg, Germany, 39130
    • Klinikum Magdeburg gemeinnützige GmbH
  • München, Germany, 81377
    • Klinikum Großhadern
  • Münster, Germany, 48149
    • Universitätsklinik Münster Innere Medizin C
  • Reinbek, Germany, 21465
    • Krankenhaus Reinbek St. Adolf-Stift
• Italy
  • Alessandria, Italy, 15100
    • Ospedale Civile Ss. Antonio E Biago
  • Ancona, Italy, 60126
    • Az. Osp-Univ. Ospedali Riuniti Umberto I-Lancisi-Salesi
  • Caserta, Italy, 81100
    • Azienda Ospedaliera S. Anna e S. Sebastiano
  • Catania, Italy, 94124
    • AOU Ferrarotti-Alessi
  • Cesena, Italy
    • Ospedale Maurizio Bufalini
  • Cuneo, Italy, 12100
    • Azienda Ospedaliera S. Croce e Carle
  • Firenze, Italy, 50134
    • Azienda Osped-Universitaria CAREGGI
  • Mercogliano, Italy, 83040
    • Casa di Cura Montevergine
  • Milan, Italy
    • Osp. Niguarda
  • Mirano, Italy, 30035
    • Ospedale Civile
  • Napoli, Italy, 80131
    • SUN Ospedale Monaldi
  • Pisa, Italy, 56126
    • Fondazione Toscana Gabriele Monasterio
  • Roma, Italy, 00169
    • Policlinico Casilino
  • Rovigo, Italy, 45100
    • Osp. S. Maria Della Misericordia
  • Sesto San Giovanni, Italy, 20099
    • IRCCS MultiMedica
  • Torino, Italy, 10126
    • A.O. Città della Salute e della Scienza di Torino Cardiologia 1 - U
  • Torino, Italy, 10126
    • A.O. Città della Salute e della Scienza di Torino Cardiologia 2 ospedaliera
  • Treviso, Italy, 31100
    • Ospedale Ca Foncello
  • Trieste, Italy, 34142
    • Azienda Ospedaliero-Universitaria Ospedali Riuniti di Trieste
  • Udine, Italy, 33100
    • Az. Osp. Univ. S. Maria della Misericordia
• Netherlands
  • Doetinchem, Netherlands, 7000
    • Slingeland Ziekenhuis
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus MC : University Medical Center
  • Schiedam, Netherlands, 3118 JH
    • Vlietland Ziekenhuis
  • Tilburg, Netherlands, 5000 LC
    • Sint Elisabeth Ziekenhuis
  • Veghel, Netherlands, 5461 AA
    • Ziekenhuis Bernhoven
  • Zwolle, Netherlands, 8000
    • Isala Klinieken
• Portugal
  • Amadora, Portugal, 2720-276
    • Hospital Professor Doutor Fernando Fonseca
  • Carnaxide, Portugal, 2799
    • Centro Hospitalar Lisboa Ocidental -Hospital de Santa Cruz (CHLO)
  • Lisboa, Portugal
    • Hospital Santa Maria
  • Porto, Portugal
    • Centro Hospitalar do Porto CHP Hospital de Santo Antonio
  • Vila Nova de Gaia, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia
• Slovenia
  • Ljubljana, Slovenia, 1000
    • Klinicni center Ljubljana
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Badalona, Spain, 08916
    • Hospital Germans Trias i Pujol
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu i Sant Pau
  • Barcelona, Spain
    • Hospital Clínico de Barcelona
  • Granada, Spain
    • H. Virgen de las Nieves
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Majadahonda, Spain, 28222
    • Hospital Puerta de Hierro
  • Malaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Oviedo, Spain, 33006
    • H. Universitario Central de Asturias
  • San Sebastian, Spain, 20014
    • Hospital Donostia
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla Sur
  • Sevilla, Spain, 41014
    • Hospital Virgen de Valme
  • Valencia, Spain
    • H. General Universit.
  • Vigo, Spain, 3204
    • CHU VIGO
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois Lausanne (CHUV)
  • Lugano, Switzerland, 6900
    • Fondazione Cardiocentro Ticino
• United Kingdom
  • Birmingham, United Kingdom
    • Queen Elizabeth Hospital
  • Cambridge, United Kingdom, CB23 3RE
    • Papworth Everard
  • Chertsey, United Kingdom
    • Ashford and St. Peter's Hospitals NHS Trust
  • Cottingham, United Kingdom, HU16 5JQ
    • Castle Hill Hospital Hull and East Yorkshire Hospitals NHS T
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • Leicester, United Kingdom, LE39QP
    • Genfield General Hospital
  • London, United Kingdom
    • King's College Hospital NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Brookwood Medical Center CardioVascular Associates
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • AZ Heart Rhythm Center
  • California
    • Culver City, California, United States, 90232
      • Brotman Medical Center
    • Newport Beach, California, United States, 92663
      • Hoag Hospital
    • San Diego, California, United States, 92942
      • Scripps Mercy Hospital
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward General Medical Center
    • Jacksonville, Florida, United States, 32204
      • St. Vincent's Healthcare
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Piedmont Hospital Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital-CAS
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Sparrow Clinical Research Institute
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
  • New York
    • New York, New York, United States, 10025
      • St. Luke's Roosevelt Hospital Center
    • New York, New York, United States, 10032
      • New York Presbyterian
    • Rochester, New York, United States, 14625
      • Rochester General Hospital
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45220
      • Good Samaritan Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • St. Francis Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19102
      • Drexel University College of Medicine
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of PA
  • South Carolina
    • Columbia, South Carolina, United States, 29204
      • Lexington Cardiology
    • Columbia, South Carolina, United States, 29204
      • Providence Cardiology d/b/a South Caroline Heart Center
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • Texas
    • Dallas, Texas, United States, 75216
      • VA North Texas Health Care System
    • Dallas, Texas, United States, 75226
      • Baylor Heart & Vascular Hospital
    • Fort Worth, Texas, United States, 76104
      • Plaza Medical Center of Fort Worth

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SonR group; SonR CRT Optimization	Device: PARADYM RF SONR; SonR CRT Optimization; Other Names: Automatic Hemodynamic CRT Optimization; Device: PARADYM RF SONR; Echocardiography Optimization; Other Names: Echo Optimization
Active Comparator: ECHO group; Echocardiographic Optimization	Device: PARADYM RF SONR; SonR CRT Optimization; Other Names: Automatic Hemodynamic CRT Optimization; Device: PARADYM RF SONR; Echocardiography Optimization; Other Names: Echo Optimization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
SonR tip lead pacing threshold	For all patients implanted with the SonRtip lead.	24 months
SonR tip lead sensing threshold	For all patients implanted with the SonRtip lead.	24 months
SonR tip lead pacing impedance	For all patients implanted with the SonRtip lead.	24 months
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
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
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
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
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
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
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
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
Report Adverse Events for both group to assess CRT effectiveness / System Safety	For all patients enrolled all Adverse Events will be reported.	24 months

Collaborators and Investigators

• Sponsor: MicroPort CRM
• Collaborators: Sorin CRM
• Investigators: Principal Investigator: Josep Brugada, Hospital Clinic of Barcelona

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: September 27, 2011
• First Submitted That Met QC Criteria: February 13, 2012
• First Posted (Estimate): February 16, 2012

Study Record Updates

• Last Update Posted (Actual): January 11, 2019
• Last Update Submitted That Met QC Criteria: January 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: sinus rhythm; CRT-D device; Severe HF (NYHA Class III or ambulatory IV); stable, optimal drug regimen
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: ITSY06 - RESPOND CRT

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: Yes