Adaptive Cardiac Resynchronization Therapy Study

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the AdaptivCRT algorithm is at least as good as manual echo based optimization in regard to patient outcomes and cardiac performance

Detailed Description
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The trial has 3 primary end points: to demonstrate that over 6-month follow-up, the proportion of the patients improved in the aCRT arm is at least as high as in the Echo arm to demonstrate that cardiac function is similar when using aCRT versus echo-optimized settings to demonstrate that aCRT does not result in inappropriate AV or VV delay settings

Official Title
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Adaptive Cardiac Resynchronization Therapy Study

Conditions
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Heart Failure

Intervention / Treatment
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* Device: Adaptive CRT (aCRT)
* Device: Echo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is willing to sign and date the study Informed Consent form Subject is at least 18 years of age (or older, if required by local law) Subject is expected to remain available for at least six months of follow-up visits Subject is indicated for a study device that will be implanted within 30 days after signing the Informed Consent form Subject has an intrinsic QRS duration greater than or equal to 120 milliseconds (documented within 30 days prior to enrollment) Subject has a left ventricular ejection fraction less than or equal to 35 percent (method per physician discretion) (documented within 180 days prior to enrollment) Subject is diagnosed with New York Heart Association (NYHA) class III or IV (within 30 days prior to enrollment) despite optimal medical therapy which is defined as: ACE-inhibitor (Angiotensin-Converting Enzyme) or Angiotensin II Receptor Blocker (ARB), if tolerated, for at least one month prior to implant, AND beta-blocker for at least three months preceding implant, if tolerated, and stable for one month, OR subject has an urgent medical need for an implantable cardioverter defibrillator (ICD) that precludes waiting the one or three months for the medication requirements for ACE inhibitor, ARB or beta-blocker Exclusion Criteria: Subject has chronic (permanent) atrial arrhythmias for which pharmacological therapy and/or cardioversion have been unsuccessful or have not been attempted Subject has existing CRT system Subject has non-intact or unstable leads Subject has medical conditions that would limit study participation (per physician discretion) Subject is enrolled in one or more concurrent studies that would confound the study results of this study as determined by Medtronic Subject has unstable angina, or experienced an acute myocardial infarction (MI) or received coronary artery revascularization (CABG) or coronary angioplasty (PTCA) (documented within 30 days prior to enrollment) Subject has a mechanical right heart valve or is scheduled to undergo valve repair or valve replacement during the course of the study Subject is post-heart transplant (subjects on the heart transplant list for the first time are not excluded) Subject has a limited life expectancy that would not allow completion of the 6 month visit Subject is pregnant (In the United States, all women of child-bearing potential must undergo a pregnancy test within seven days prior to aCRT download into device) Subject meets the exclusion criteria required by local law

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adaptive CRT (aCRT) arm<br>Intervention: Cardiac resynchronization therapy (CRT-D) with Adaptive CRT algorithm ON | Device: Adaptive CRT (aCRT)<br>* Adaptive CRT (aCRT) is an algorithm, which provides ambulatory adjustment of pacing configuration (LV-only or BiV) and AV and VV delays based on periodic automatic evaluation of electrical conduction to optimize cardiac function<br>* Other names: aCRT;|
| Active Comparator: Echo-optimized arm<br>Intervention: Cardiac resynchronization therapy (CRT-D) with standard biventricular pacing (Adaptive CRT algorithm OFF) | Device: Echo<br>* Standard BiV pacing with settings optimized using a standardized echocardiographic protocol<br>* Other names: Control;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Improved Heart Failure Outcomes Clinical Composite Score | Patients considered worsened if they died, were hospitalized with worsening heart failure (HF), crossed over to other arm, demonstrated worsening in New York Heart Association (NYHA) functional class, or reported moderately/markedly worse on 'patient global assessment' compared to before CRT implant. Patients are improved if they are not worsened and have an improved NYHA or reported moderately/markedly improved on the 'patient global assessment' compared to before CRT implant Global assessment question for the patient: Specifically in reference to your heart failure symptoms, how do you feel today as compared to how you felt before your CRT system was implanted? O Markedly improved O Moderately improved O Mildly improved O No change O Slightly worse O Moderately worse O Markedly worse | randomization to six month visit | 
| Correlation Between Aortic Velocity Time Integral (AoVTI) at Adaptive CRT and Echo-optimized Device Settings | Correlation between aortic velocity time integral (AoVTI) at Adaptive CRT and echo-optimized device settings. AoVTI is an echocardiographic representative of stroke volume and cardiac performance. | randomization visit and six month visit | 
| Percentage of Patients With a Safety Event (Inappropriate AV or VV Delay Settings Related to the aCRT Feature) | For each subject, the Adaptive CRT-determined AV and VV delay settings from randomization up to 183-days post-randomization were evaluated to identify any period of 28-days with a wide delay range (>60 ms) | randomization to 6 months post randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right Ventricular Pacing Percentage | The percentage of time the right ventricle is paced by the device | implant to six months post randomization | 
| Change in Left Ventricular End Systolic Volume Index (LVESVi) | Change in left ventricular end systolic volume index (LVESVi). | baseline to six month visit | 
| Change in Left Ventricular Ejection Fraction (LVEF) |  | baseline to six month visit | 
| Change in New York Heart Association (NYHA) Classification | The New York Heart Association (NYHA) Functional Classification places patients in one of four categories based on how much they are limited during physical activity. Class - Patient Symptoms I - No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea (shortness of breath). II- Slight limitation of physical activity. Comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea (shortness of breath). III- Marked limitation of physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. IV- Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. | baseline to six month visit | 
| Change in Distance Walked During the Six Minute Hall Walk |  | baseline to six month visit | 
| Change in Quality of Life Measured by the Minnesota Living With Heart Failure Questionnaire (MLWHF) | The MLWHF is a 21 question survey. Scores range from 0-105, with lower scores indicating better health. | baseline to six month visit |