Cardiac Resynchronization Therapy in Previously Untreatable and High Risk Upgrade Patients (SOLVE-CRT)

Stimulation Of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy in Non-Responders, Previously Untreatable and High Risk Upgrade Patients (SOLVE CRT)

This study is a prospective, multi-center, pivotal trial to study the safety and efficacy of the WiSE-CRT System for Cardiac Re-synchronization Therapy.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure
• Intervention / Treatment: Device: WiSE System

Detailed Description

The WiSE-CRT System is an implantable cardiac pacing system capable of delivering pacing energy to the left ventricle of the heart without using a pacing lead.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • Royal Prince Alfred Hospital
  • Canberra
    • Garran, Canberra, Australia, 2605
      • Canberra Hospital
  • New South Wales
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
    • Wahroonga, New South Wales, Australia
      • Sydney Adventist Hospital
  • Queensland
    • Chermside, Queensland, Australia
      • The Prince Charles Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Heart
    • Parkville, Victoria, Australia
      • Royal Melbourne Hospital / Royal Hobart Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• France
  • Grenoble, France
    • CHU Grenoble - Hopital Michallon Service de Cardiologie
  • Paris, France
    • Centre Cardiologique du Nord
  • Rennes, France
    • CHU-Hopital Pontchaillou
• Germany
  • Bernau, Germany, 16321
    • Immanuel Klinikum Bernau - Herzzentrum Brandenburg
  • Erlangen, Germany, 91054
    • Universitatsklinikum Erlangen
  • Hamburg, Germany
    • Universitäres Herzzentrum Hamburg (UKE Hamburg) GmbH (UHZ)
• Italy
  • Bologna, Italy, 40138
    • Policlinico S. Orsola
  • Monza, Italy
    • Ospedale San Gerardo
• Netherlands
  • Zwolle, Netherlands, 8025 AB
    • Isala Hartcentrum
• United Kingdom
  • Liverpool, United Kingdom, L14 3PE
    • Liverpool Heart and Chest Hospital
  • London, United Kingdom, EC1A 7BE
    • Barts Heart Centre
  • London, United Kingdom, SE1 7EH
    • St. Thomas Hospital
  • Manchester, United Kingdom, M13 9WL
    • Manchester Heart Centre
  • Middlesbrough, United Kingdom, TS4 3BW
    • James Cook University Hospital
  • Oxford, United Kingdom, OX3 9DU
    • John Radcliffe Hospital
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research
  • California
    • La Jolla, California, United States, 92037
      • University of California, San Diego
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Broward Health Medical Center
    • Jacksonville, Florida, United States, 32204
      • St. Vincent's HealthCare
    • Lakeland, Florida, United States, 33805
      • Watson Clinic
    • Naples, Florida, United States, 34102
      • Naples Community Hospital
    • Saint Petersburg, Florida, United States, 33709
      • Northside Hospital and Heart Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Healthcare
    • Atlanta, Georgia, United States, 30309
      • Piedmont Heart Institute
  • Illinois
    • Springfield, Illinois, United States, 62769
      • Prairie Heart
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • St. Vincent's Hospital and Healthcare Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
    • Kansas City, Kansas, United States, 63131
      • Saint Luke's Health System Kansas City
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70816
      • Ochsner Medical Center - Baton Rouge
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Canton, Michigan, United States, 48188
      • Michigan Heart
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Hazel Park, Michigan, United States, 48030
      • William Beaumont Hospital
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55102
      • United Heart and Vascular Clinic
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Physicians Clinic Heart Consultants
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers University
    • Pomona, New Jersey, United States, 08240
      • Atlanticare Regional Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Oregon
    • Springfield, Oregon, United States, 97477
      • PeaceHealth
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Health, Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC Heart and Vascular Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Gazes Research Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston
    • Houston, Texas, United States, 77030
      • Texas Heart Institute
    • Plano, Texas, United States, 75093
      • The Heart Hospital Baylor Plano
    • Sugar Land, Texas, United States, 77479
      • Houston Methodist
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Healthcare
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion/Exclusion:

Inclusion Criteria

1. Patient with a class I or IIa (1) or (2) indication for implantation of a CRT-D device according to current available guidelines (with additional QRS criteria on Class IIa (1)):

   1. Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms
   2. Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms
   3. Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms

2. Patient is a:

   1. 'Non-responder' [Not Enrolling]: Patients who have a CRT system that is functional and despite an adequate trial of Guideline Directed Medical Therapy (GDMT) and attempts at optimal device programming the patient has not responded to therapy for a minimum of 6 months. Non-response is defined as:

      • EF has remained unchanged or worsened (defined as < 5% increase since implant), and
      • The patient's clinical status based in the totality of available clinical evidence (such as NYHA Class, exercise tolerance, QOL, or global assessment) has remained unchanged or worsened, as determined by the local Site Enrollment Committee

      OR

   2. 'Previously Untreatable': Patients who have a full or partial CRT system, who meet general inclusion criteria and are deemed as 'previously untreatable' for one of the following reasons:

   i. Patients in whom CS lead implantation for CRT has failed

   • CS lead implant was attempted but abandoned due any of the following: difficult CS access or anatomy, inadequate lead location, inadequate pacing thresholds, persistent phrenic nerve pacing, or other procedural challenges

   ii. CS lead implanted but has been programmed OFF

   • LV lead that was implanted but not operational includes patients in whom the LV lead is inoperative or programmed off due to improper function such as high threshold, non-capture, phrenic nerve pacing, lead failure, lead dislodgement, or sub-optimal LV lead location

   OR

   c. 'High Risk Upgrade:

   Patients who have a relative contraindication to CS lead implant, due to:

   • venous occlusion or lesion precluding implant
   • pocket infection risk (at co-implanted device site)
   • considered high risk for CS implant due to co-morbidities
3. Patients on a stable Guideline Directed Medical Therapy (GDMT)
4. Patient must be 18 years old or over
5. Patient has signed and dated informed consent
6. Patient has suitable anatomy for implant of the WiSE CRT System (e.g. adequate acoustic window, LV wall thickness in target implant area ≥ 5 mm, absence of LV wall structural abnormalities which may preclude implant)

Exclusion Criteria

Patients who meet any one of these criteria will be excluded from the investigation:

1. Pure RBBB
2. LVEDD ≥ 8cm
3. Non-ambulatory or unstable NYHA class IV
4. Contraindication to heparin, chronic anticoagulants or antiplatelet agents
5. Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy
6. Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days.
7. Patients with planned or expected lithotripsy treatment post implant
8. Life expectancy of < 12 months
9. Chronic hemodialysis
10. Stage 4 or 5 renal dysfunction defined as eGFR < 30
11. Grade 4 mitral valve regurgitation
12. Noncardiac implanted electrical stimulation therapy devices
13. Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach
14. Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach
15. Unstable angina, acute MI, CABG, or PTCA within the past 1 month
16. Correctable valvular disease that is the primary cause of heart failure
17. Recent CVA or TIA (within the previous 3 months)
18. Patients with a history of paroxysmal or persistent atrial fibrillation/flutter are excluded if they have had a documented AF episode > 30 min or a cardioversion in the past 1 month.
19. Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%)
20. Already included in another clinical study that could confound the results of this study
21. Pregnancy
22. Known drug or alcohol addiction or abuse
23. Moderate or severe aortic stenosis
24. Subject unable to attend follow-up at the investigative center or unable, for physical or mental reasons, or to comply with the trial's procedures
25. For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment; WiSE System therapy ON with Guideline Directed Medical Therapy	Device: WiSE System; The WiSE System is an implantable cardiac system to provide LV pacing stimulation in conjunction with a co-implanted system that provides right ventricular stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety	Freedom from Procedure and Device System related Type 1 Complications	6 Months
Primary Efficacy 1	Mean relative % change in Left Ventricular End Systolic Volume (LVESV) baseline to 6 Months.	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Secondary Efficacy 1	Electrode Acoustic Pacing Capture Threshold (APCT) measured at the 6-month follow-up post-implant visit	6 Months
Secondary Efficacy 2	Electrode Acoustic Pacing Capture Threshold Stability (APCT Stability) measured from pre-discharge through the 6-month follow-up post-implant visit	6 Months
Secondary Efficacy 4	EF responder analysis for ≥ 5% absolute increase from baseline to 6 months.	6 months
Secondary Efficacy 5	KCCQ responder analysis for ≥ 5 points absolute increase from baseline to 6 months	6 months
Secondary Efficacy 3	% Bi-ventricular pacing at 6 months	6 months

Collaborators and Investigators

• Sponsor: EBR Systems, Inc.
• Investigators: Principal Investigator: Jagmeet Singh, MD, PhD, Massachusetts General Hospital; Principal Investigator: Mary N Walsh, MD, MACC, St. Vincent Heart Center

Publications and helpful links

General Publications

• Singh JP, Abraham WT, Auricchio A, Delnoy PP, Gold M, Reddy VY, Sanders P, Lindenfeld J, Rinaldi CA. Design and rationale for the Stimulation Of the Left Ventricular Endocardium for Cardiac Resynchronization Therapy in non-responders and previously untreatable patients (SOLVE-CRT) trial. Am Heart J. 2019 Nov;217:13-22. doi: 10.1016/j.ahj.2019.04.002. Epub 2019 Apr 9.

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: September 27, 2016
• First Submitted That Met QC Criteria: September 29, 2016
• First Posted (Estimated): October 3, 2016

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: CSP-03035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes