Investigational Device Exemption (IDE) Study for the Approval of Closed Loop Stimulation (CLS) and Cardiac Resyncronization Pacing Therapies (CRT) for the Treatment of Atrial Fibrillation (AF) With Ablate and Pace

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the safety and effectiveness of biventricular pacing over conventional right ventricular pacing in patients with persistent or permanent, symptomatic atrial fibrillation undergoing atrioventricular (AV) node ablation and permanent pacing therapy.

Detailed Description
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This study is a multi-center, prospective, randomized, blinded trial. The study will consist of approximately 265 patients who require treatment of persistent or permanent, symptomatic atrial fibrillation by atrioventricular (AV) node ablation and permanent pacing therapy i.e. Ablate and Pace therapy. All patients enrolled into the clinical study will be randomly assigned to one of three groups using a randomization ratio of 2:2:1. Patients will be assigned to receive either biventricular (biV) pacing with CLS-based rate adaptive pacing using the legally marketed Protos DR/CLS (Group 1), or biventricular pacing with accelerometer-based rate adaptive pacing using the Stratos LV (Group 2), or right ventricular (RV) pacing with accelerometer-based rate adaptive pacing using the Stratos LV (Group 3). Patients in all three groups will be implanted with legally marketed right and left ventricular pacing leads. The patients, the core lab used to interpret the echocardiographic data and the Clinical Events Committee adjudicating crossover, patient death and congestive heart failure (CHF) hospitalizations will be blinded to the randomization assignment.

Official Title
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AVAIL CLS/CRT: AV-node Ablation With CLS and CRT Pacing Therapies for the Treatment of AF

Conditions
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Atrial Fibrillation, Congestive Heart Failure

Intervention / Treatment
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* Device: Protos DR/CLS and Stratos LV CRT pacemakers


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the indications for therapy Persistent, symptomatic AF with poorly controlled rapid ventricular rates or permanent, symptomatic AF with poorly controlled rapid ventricular rates. Eligible for AV nodal ablation and permanent pacemaker implantation NYHA Class II or III heart failure Age ≥ 18 years Understand the nature of the procedure Ability to tolerate the surgical procedure required for implantation Give informed consent Able to complete all testing required by the clinical protocol Available for follow-up visits on a regular basis at the investigational site Exclusion Criteria: Meet one or more of the contraindications Have a life expectancy of less than six months Expected to receive heart transplantation within six months Enrolled in another cardiovascular or pharmacological clinical investigation Patients with an ICD, or being considered for an ICD Patients with previously implanted biventricular pacing systems Patients with previously implanted single or dual chamber pacing system with > 50% documented ventricular pacing Patients with previous AV node ablation Six-minute walk test distance greater than 450 meters Any condition preventing the patient from being able to perform required testing Presence of another life-threatening, underlying illness separate from their cardiac disorder Conditions that prohibit placement of any of the lead systems

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Biventricular pacing group with Closed Loop Stimulation rate adaptation (Protos CLS device) | Device: Protos DR/CLS and Stratos LV CRT pacemakers<br>* Protos DR/CLS is a dual chamber pacemaker with CLS rate adaption, Stratos LV is a biventricular pacemaker with accelerometer based rate adaption<br>* Other names: Protos DR/CLS dual chamber pacemaker;|
| Active Comparator: 2<br>Biventricular pacing group with accelerometer based rate adaption (Stratos LV device) | Device: Protos DR/CLS and Stratos LV CRT pacemakers<br>* Protos DR/CLS is a dual chamber pacemaker with CLS rate adaption, Stratos LV is a biventricular pacemaker with accelerometer based rate adaption<br>* Other names: Protos DR/CLS dual chamber pacemaker;|
| Active Comparator: 3<br>Right Ventricular pacing group with accelerometer based rate adaption (Stratos LV device) | Device: Protos DR/CLS and Stratos LV CRT pacemakers<br>* Protos DR/CLS is a dual chamber pacemaker with CLS rate adaption, Stratos LV is a biventricular pacemaker with accelerometer based rate adaption<br>* Other names: Protos DR/CLS dual chamber pacemaker;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Percentage Improvement From Baseline of the 6-minute Walk Test Distance and Minnesota Living With Heart Failure Quality of Life Score at 6-months | Combined, average percentage improvement in 6-minute walk test distance and Minnessota Living With Heart Failure Quality of Life score from baseline to 6-month follow-up for the Protos DR/CLS (Group 1) and Stratos LV (Group 2) compared with the active control (Group 3). The 6-minute walk test is a test that measure how far a patient can walk in 6 minutes in a standardized walking course. Percent Change (0% (worst)-100% (best)) | Change from baseline to six months post-procedure | 
| Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure | Complication-free rate was evaluated in an equivalence (non-inferiority) format compared to a target of 85% minus delta (10%), where delta is the clinically significant difference for establishing equivalence. This endpoint evaluated system-related complications. | At six months post-procedure | 
| Number of Participants Free of System-related Complications (Related to the Device, Leads, or Implant Procedure) at 6 Months Post-procedure | Complication-free rate was evaluated in an equivalence (non-inferiority) format compared to a target of 85% minus delta (10%), where delta is the clinically significant difference for establishing equivalence. This endpoint evaluated system-related complications. All Stratos systems (in both the biV and RV pacing arms) were evaluated together as pre-specified in the protocol. | At six months post-procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Six-minute Walk Test |  | Change from baseline to 6 months post-procedure | 
| Change in Quality Of Life (QOL) Score Over 6 Months Calculated as QOL Score at Baseline - QOL Score at 6 Months | Quality of Life was evaluated using the Minnesota Living with Heart Failure (MLHF) Quality of Life (QOL) Questionnaire.The questionnaire consists of 21 questions to measure the subjects' perception of how their HF and its treatment affected their ability to live as they wanted during the last month. The questions describe different ways in which some people are affected (i.e. physical, socioeconomic, and psychological impairments). If a question does not apply to a subject or is not related to their HF, then they can answer with a 0. If it does apply to them, then they can rate (from 1 to 5) how much it has affected them. From the 21 questions, the lowest possible total score is 0, and the highest possible total score is 105. A lower score is desirable. This outcome was calculated as QOL score at baseline minus QOL score at 6 months. Therefore, a positive change in QOL score represents an improvement in quality of life, while a negative change in QOL score represents a worsening. | Change from baseline to six months post-procedure | 
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Ejection Fraction |  | Change from baseline to six months post-procedure | 
| Changes in New York Heart Association (NYHA) Classification | The purpose is to evaluate the change in the participant's NYHA classification. There are four NYHA classes: Class I: Patients with cardiac disease, but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. Class II: Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain. Class III: Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of cardiac insufficiency or of anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased. | Change from baseline to six months post-procedure | 
| Percentage of Patients With Congestive Heart Failure (CHF) Related Hospitalizations |  | At six months post-procedure | 
| Mortality Rate |  | At six months post-procedure | 
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Atrial Volume |  | Change from baseline to six months post-procedure | 
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular Mass |  | Change from baseline to six months post-procedure | 
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Systolic Volume |  | Change from baseline to six months post-procedure | 
| Cardiac Remodeling Assessments by Echocardiography - Change in Left Ventricular End Diastolic Volume |  | Change from baseline to six months post-procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pacemaker, atrial fibrillation, AV node ablation, congestive heart failure