Cardiac Resynchronization Therapy in Previously Untreatable and High Risk Upgrade Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Heart Failure

Intervention / Treatment
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* Device: WiSE System


Participation Criteria
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Eligibility Criteria
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Inclusion/Exclusion: Inclusion Criteria 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)): Class I: NYHA II, III, IV, EF ≤ 35%, LBBB, QRS ≥ 150ms Class IIa (1): NYHA II, III, IV, EF≤ 35%, LBBB, QRS ≥ 130 to < 150ms Class IIa (2): NYHA II, III, IV, EF≤ 35%, non-LBBB, QRS ≥ 150ms Patient is a: '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 '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 Patients on a stable Guideline Directed Medical Therapy (GDMT) Patient must be 18 years old or over Patient has signed and dated informed consent 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: Pure RBBB LVEDD ≥ 8cm Non-ambulatory or unstable NYHA class IV Contraindication to heparin, chronic anticoagulants or antiplatelet agents Triple anticoagulant patients who cannot tolerate peri-procedural stopping of anticoagulation therapy Attempted device implant (pacemaker, ICD, CRT, LV lead) or successful co-implant within prior 30 days. Patients with planned or expected lithotripsy treatment post implant Life expectancy of < 12 months Chronic hemodialysis Stage 4 or 5 renal dysfunction defined as eGFR < 30 Grade 4 mitral valve regurgitation Noncardiac implanted electrical stimulation therapy devices Patients with a prosthetic aortic valve in which the electrode cannot be implanted via a transseptal approach Patients with a prosthetic mitral valve in which the electrode cannot be implanted via a retrograde aortic approach Unstable angina, acute MI, CABG, or PTCA within the past 1 month Correctable valvular disease that is the primary cause of heart failure Recent CVA or TIA (within the previous 3 months) 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. Patients with permanent AF are excluded if they have intact AV node conduction (RV pacing <95%) Already included in another clinical study that could confound the results of this study Pregnancy Known drug or alcohol addiction or abuse Moderate or severe aortic stenosis 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 For Part II Randomized patients only, those who will not tolerate being randomized to the Control Group for 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>WiSE System therapy ON with Guideline Directed Medical Therapy | Device: WiSE System<br>* 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.<br>|

What is the study measuring?
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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 3 | % Bi-ventricular pacing at 6 months | 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 |