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

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by Sorin Group
Sponsor:
Information provided by:
Sorin Group
ClinicalTrials.gov Identifier:
NCT01534234
First received: September 27, 2011
Last updated: December 13, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Heart Failure NYHA Class III
Device: PARADYM RF SONR
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Clinical Trial of the SonRtip Lead and Automatic AV-VV Optimization Algorithm in the PARADYM RF SonR CRT-D

Resource links provided by NLM:


Further study details as provided by Sorin Group:

Primary Outcome Measures:
  • 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%. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    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.


  • Evaluation of Lead Safety: Acute SonRTipLead Complication-Free Rate (at 3 months) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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.

  • Evaluation of Lead Safety: Chronic SonRTipLead Complication-Free Rate (from 3 months to 12 months) [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Evaluation of CRT effectiveness and CRT Safety: evaluation of Mortality and HF hospitalizations at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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

  • Evaluation of CRT effectiveness and CRT therapy: Proportion of patients worsened at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    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

  • SonR tip lead pacing threshold [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    For all patients implanted with the SonRtip lead.

  • SonR tip lead sensing threshold [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    For all patients implanted with the SonRtip lead.

  • SonR tip lead pacing impedance [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    For all patients implanted with the SonRtip lead.

  • Evaluation of CRT effectiveness and CRT and System Safety: Report deaths for any cause [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    The report of the deaths occurred consists of the percentage of dead patients, the causes of death, the time to death, the survival curves.

  • Report Heart Failure-related events to assess CRT effectiveness [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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)

  • Report Quality of life (QOL) improvement to assess CRT effectiveness (percentage of patients with improvements in QOL) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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

  • Report NYHA class improvement to assess CRT effectiveness (the percentage of patients with improved in NYHA class) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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

  • Evaluation of CRT effectiveness: Report echocardiographic parameters trend at M12 [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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

  • Evaluation of SonR CRT Optimization Effectiveness - Superiority by assessment the proportion of responder patients in SonR group [ Time Frame: 18/24 months ] [ Designated as safety issue: No ]
    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).

  • Evaluation of the time spent for CRT optimization by the physician on optimization in each group (sonR and ECHO) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    The amount of time (mean, median, standard deviation, minimum, maximum)in each group will be evaluated in all patients implanted

  • Evaluation of the Number of re-optimizations performed in both groups (SonR and ECHO) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    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).

  • Report Adverse Events for both group to assess CRT effectiveness / System Safety [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    For all patients enrolled all Adverse Events will be reported.


Estimated Enrollment: 1032
Study Start Date: January 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: SonR group
SonR CRT Optimization
Device: PARADYM RF SONR
SonR CRT Optimization
ECHO group
Echocardiographic Optimization
Device: PARADYM RF SONR
Echocardiography Optimization

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01534234

Contacts
Contact: Alberto Borri Brunetto, Study manager +390161487211 alberto.borri.brunetto@sorin.com

  Show 106 Study Locations
Sponsors and Collaborators
Sorin Group
Investigators
Principal Investigator: Josep BRUGADA Hospital Clinic de Barcelona
  More Information

No publications provided by Sorin Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT01534234     History of Changes
Other Study ID Numbers: ITSY06 - RESPOND CRT
Study First Received: September 27, 2011
Last Updated: December 13, 2013
Health Authority: United States: Food and Drug Administration
Australia: Human Research Ethics Committee
Austria: Ethikkomission
France: Comité de protection des personnes
Germany: Ethics Commission
Italy: Ethics Committee
Portugal: Health Ethic Committee
Spain: Ethics Committee
Switzerland: Ethics Commission
United Kingdom: Research Ethics Committee
Slovenia: Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Sorin Group:
CRT-D device
Severe HF (NYHA Class III or IV)
stable, optimal drug regimen
sinus rhythm

Additional relevant MeSH terms:
Heart Failure
Cardiovascular Diseases
Heart Diseases

ClinicalTrials.gov processed this record on October 29, 2014