Evaluation of ACUITY™ X4 Quadripolar Coronary Venous Leads and RELIANCE™ 4-FRONT Defibrillation Leads

Study Overview
=================
Brief Summary
-----------------
The objective of the NAVIGATE X4 Clinical Study is to gather data to establish the safety, performance and effectiveness of the ACUITY™ X4 quadripolar coronary venous leads and the RELIANCE 4-FRONT™ ventricular defibrillation leads to satisfy FDA requirements for pre-market submission. Additionally, data from this study will be used to support post-market approval requirements for the ACUITY X4 and RELIANCE 4-FRONT leads.

Official Title
-----------------
Evaluation of ACUITY™ X4 Quadripolar Coronary Venous Leads and RELIANCE™ 4-FRONT Defibrillation Leads: NAVIGATE X4

Conditions
-----------------
Cardiac Resynchronization Therapy

Intervention / Treatment
-----------------
* Device: ACUITY X4 quadripolar coronary venous lead and RELIANCE 4-FRONT defibrillation lead


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects indicated for a CRT-D that fulfill one of the following 5 criteria[1]: Subject with left ventricular ejection fraction (LVEF) less than or equal to 35%, sinus rhythm, left bundle branch block (LBBB) with a QRS duration greater than or equal to 150 ms, and a NYHA class II, III or ambulatory IV symptoms on Guideline-Directed Medical Therapy (GDMT)* Subject with LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT* Subject with LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with a QRS duration greater than or equal to 150 ms, and NYHA class III/ ambulatory class IV symptoms on GDMT* Subject with atrial fibrillation and LVEF less than or equal to 35% on GDMT* if a) the subject requires ventricular pacing or otherwise meets CRT criteria [listed here] and b) AV nodal ablation or pharmacologic rate control will allow near 100% ventricular pacing with CRT Subject on GDMT* who have LVEF less than or equal to 35% and are undergoing new device placement with anticipated requirement for significant (>40%) ventricular pacing *GDMT = Guideline-directed medical therapy (formerly known as optimal pharmaceutical therapy (OPT)), represents optimal medical therapy as defined by ACCF/ AHA guideline-recommended therapies (primarily Class I) Subject is intended to receive the ACUITY X4 LV lead and RELIANCE 4-FRONT RV lead (optional in Study Phase 1) and BSC CRT-D with quadripolar header as their initial (de novo) cardiac implants Subject is willing and capable of providing informed consent (which can include the use of a legally authorized representative [LAR] for documentation of informed consent) and participating in all testing associated with this investigation at an approved center and at the intervals defined by this protocol Subject is age 18 or above, or of legal age to give informed consent specific to state and national law Exclusion Criteria: Subjects who meet any one of the following criteria will be excluded from this clinical study. Subject has a known or suspected sensitivity to dexamethasone acetate (DXA) Subject has a mechanical tricuspid heart valve Subject is enrolled in any other concurrent study, with the exception of local mandatory governmental registries and observational studies/registries* that are not in conflict and do not affect the following: Schedule of procedures for the Study (i.e. should not cause additional or missed visits); Study outcome (i.e. involve medications that could affect the heart rate of the subject); Conduct of the Study per good clinical practice (GCP) / International Organization for Standardization (ISO) 14155:2011/ 21 Code of Federal Regulations (CFR) 812, local regulations Subject is currently on the active heart transplant list Subject has a documented life expectancy of less than twelve months Women of childbearing potential who are or might be pregnant at the time of study enrollment or CRT-D System implant (method of assessment upon physician's discretion) Subjects currently requiring chronic dialysis *Sponsors of such studies/registries should be informed and Boston Scientific must be informed by the investigator about the parallel conduct of these projects in the subject and of the project's basic nature. The decision if a desired mandatory governmental registry or observational study/ registry is in conflict with this exclusion criterion is up to the enrolling investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Every subject had access to two study devices and were followed as a single group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enrolled Patients<br>Subjects undergo an implant procedure to receive at least one investigational lead -- ACUITY X4 left ventricular (LV) CRT lead, RELIANCE 4-FRONT right ventricular (RV) ICD lead | Device: ACUITY X4 quadripolar coronary venous lead and RELIANCE 4-FRONT defibrillation lead<br>* The ACUITY X4 leads are intended for chronic left ventricular pacing and sensing. The leads have 3 tip configuration designs (straight tip, short tip spiral, and long tip spiral), which is intended to provide choices for patients with different anatomies. The RELIANCE 4-FRONT leads are designed for right-side heart applications within the ventricle, atrium, and superior vena cava. It is intended for permanent sensing, pacing, and defibrillation when used with a compatible implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D). Subjects were allowed to receive both the ACUITY X4 and RELIANCE 4-FRONT lead.<br>* Other names: RV defibrillation Lead;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of ACUITY X4 Spiral Leads Free From Complication Through 6 Months | Lead-related complication-free rate of ACUITY X4 Spiral Leads from implant through 6 months post implant. | Implant through 6 months | 
| Percentage of ACUITY X4 Straight Leads Free From Complication Through 6 Months | Lead-related complication-free rate of ACUITY X4 Straight Leads from implant through 6 months post implant. | Implant through 6 months | 
| Percentage of ACUITY X4 Leads With Acceptable Pacing Capture Thresholds (PCT) | PCT measurements in the programmed configuration were collected at 3 months post-implant. Programmed configuration refers to the pacing configuration that was selected by the physician to provide LV pacing therapy. The percentage of measurements with PCT ≤ 2.5 V were calculated. | Implant through 3 months | 
| Percentage of ACUITY X4 Spiral Leads With Acceptable Pacing Capture Thresholds (PCT) Using the Best Proximal Electrode | PCT measurements in the in the proximal zone (electrodes 2, 3, 4) were collected at 3 months post-implant. Physician investigators were instructed to use the best proximal electrode (E2, E3 or E4) as the cathode and the RV lead coil or pulse generator as the anode; best was defined as the electrode with the lowest PCT without phrenic nerve stimulation. The percentage of measurements with PCT ≤ 2.5 V were calculated. | 3 months | 
| Percentage of RELIANCE 4-FRONT Leads Free From Complication Through 3 Months | Lead-related complication-free rate of RELIANCE 4-FRONT Leads from implant through 3 months post implant. | Implant through 3 months | 
| Percentage of RELIANCE 4-FRONT Leads Free From Complication From 3 Through 24 Months | Lead-related complication-free rate of RELIANCE 4-FRONT Leads from 3 through 24 months post implant. | 3 months through 24 months | 
| Mean Pacing Capture Threshold (PCT) of RELIANCE 4-FRONT Leads at 3 Months | PCT measurements from RELIANCE 4-FRONT leads were collected at 3 months post-implant. Measurements were performed using 0.5 millisecond pulse width. | Implant through 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Sensed Amplitude of ACUITY X4 Spiral Leads at 3 Months | Sensed amplitude measurements from ACUITY X4 Spiral leads were collected at 3 months post-implant. | 3 months | 
| Mean Sensed Amplitude of ACUITY X4 Straight Leads at 3 Months | Sensed amplitude measurements from ACUITY X4 Straight leads were collected at 3 months post-implant. | 3 months | 
| Mean Pacing Impedance of ACUITY X4 Spiral Leads at 3 Months | Pacing impedance measurements from ACUITY X4 Spiral leads were collected at 3 months post-implant. | 3 months | 
| Mean Pacing Impedance ACUITY X4 Straight Leads at 3 Months | Pacing impedance measurements from ACUITY X4 Straight leads were collected at 3 months post-implant. | 3 months | 
| Mean Detection Time of Induced Ventricular Tachycardia / Ventricular Fibrillation (VT/VF) Episodes Using RELIANCE 4-FRONT Leads | The mean detection time, in seconds, of induced VT/VF episodes occurring within 30 days of implant were evaluated. Subjects were required to implanted with RELIANCE 4-FRONT leads to be evaluated. | Within 30 days of implant | 
| Mean Sensed Amplitude of RELIANCE 4-FRONT Leads at 3 Months | Sensed amplitude measurements from RELIANCE 4-FRONT leads were collected at 3 months post-implant. | 3 months | 
| Mean Pacing Impedance of RELIANCE 4-FRONT Active Fixation Leads at 3 Months | Pacing impedance measurements from RELIANCE 4-FRONT Active Fixation leads were collected at 3 months post-implant. | 3 months | 
| Mean Pacing Impedance of RELIANCE 4-FRONT Passive Fixation Leads at 3 Months | Pacing impedance measurements from RELIANCE 4-FRONT Passive Fixation leads were collected at 3 months post-implant. | 3 months | 
| Percentage of Successfully Converted Induced Ventricular Tachycardia / Ventricular Fibrillation (VT/VF) Episodes Using RELIANCE 4-FRONT Leads | Ventricular Tachyarrhythmia (VT/VF) Shock Conversion Efficacy, analyzed within 30 days of implant | Within 30 days of implant |