AdaptResponse Clinical Trial

Study Overview
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Brief Summary
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The purpose of this clinical study is to test the hypothesis that market released Cardiac Resynchronization Therapy (CRT) devices which contain the AdaptivCRT® (aCRT) algorithm have a superior outcome compared to standard CRT devices in CRT indicated patients with normal atrio-ventricular (AV) conduction and left bundle branch block (LBBB).

Official Title
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AdaptResponse Clinical Trial

Conditions
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Heart Failure With Left Bundle Branch Block

Intervention / Treatment
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* Device: aCRT ON
* Device: aCRT OFF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is willing to sign and date the study Patient Informed Consent Form. Subject is indicated for a CRT device according to local guidelines. Sinus Rhythm at time of enrollment Complete Left Bundle Branch Block (LBBB) as documented on an ECG (within 30 days prior to enrollment). Strauss Criteria used for LBBB. Intrinsic, normal AV conduction as documented on an ECG by a PR interval less than or equal to 200ms (within 30 days prior to enrollment). Left ventricular ejection fraction less than or equal to 35% (documented within 180 days prior to enrollment). NYHA class II, III or IV (documented within 30 days prior to enrollment) despite optimal medical therapy. Optimal medical therapy is defined as maximal tolerated dose of Beta-blockers and a therapeutic dose of ACE-I, ARB or Aldosterone Antagonist. Exclusion Criteria: Subject is less than 18 years of age (or has not reached minimum age per local law). Subject is not expected to remain available for at least 2 years of follow-up visits. Subject has permanent atrial arrhythmias for which pharmacological therapy and/or cardioversion have been unsuccessful or have not been attempted Subject is, or previously has been, receiving cardiac resynchronization therapy. Subject is currently enrolled or planning to participate in a potentially confounding drug or device trial during the course of this study. Co-enrollment in concurrent trials is only allowed when documented pre-approval is obtained from the Medtronic study manager. Subject has unstable angina, or experienced an acute myocardial infarction (MI) or received coronary artery revascularization (CABG) or coronary angioplasty (PTCA) within 30 days prior to enrollment. Subject has a mechanical tricuspid 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 due to non-cardiac causes that would not allow completion of the study. Subject is pregnant (if required by local law, women of child-bearing potential must undergo a pregnancy test within seven days prior to device implant). Subject meets any 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aCRT ON<br>The aCRT algorithm has been developed to provide RV-synchronized LV pacing when intrinsic AV conduction is normal or BiV pacing otherwise | Device: aCRT ON<br>* CRT device with AdaptivCRT enabled (AdaptivBiV and LV)<br>|
| Active Comparator: aCRT OFF<br>Standard CRT | Device: aCRT OFF<br>* CRT device with AdaptivCRT disabled<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined Endpoint of All-cause Mortality and Intervention for Heart Failure Decompensation | The first occurrence of death or intervention for heart failure decompensation (defined as an event requiring invasive intervention or inpatient hospitalization). | from subject randomization until the first occurrence of death or intervention for heart failure decompensation, median follow-up 4.9 years (max. follow-up 8.1 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause Mortality | All-cause mortality in the aCRT ON group vs the aCRT OFF group | from subject randomization until the occurrence of death, median follow-up 4.9 years (max. follow-up 8.1 years) | 
| Percent of Patients With Interventions for Heart Failure Decompensation | First occurence of intervention for heart failure decompensation is defined as an event requiring invasive intervention or inpatient hospitalization. | from subject randomization until the first occurrence of intervention for heart failure decompensation, median follow-up 4.9 years (max. follow-up 8.1 years) | 
| Clinical Composite Score | The Clinical Composite Score (CCS) classifies patients according their clinical status at 6 months post randomization into categories Improved, Unchanged, and Worsened. A patient is classified Worsened in case of death, hospitalization for worsening heart failure, worsened NYHA class (using last observation carried forward), or worsened status on the Global Assessment Score. Also patients that exit the study or cross over because of worsening heart failure are classified Worsened. A patient is classified Improved when not Worsened and there is an improvement in NYHA class or Global Assessment Score. Patients that are not Worsened or Improved are Unchanged. | CCS at 6 month post randomization | 
| Atrial Fibrillation | Occurrence of atrial fibrillation lasting >6 hours in one day | from subject randomization until the first occurrence of atrial fibrillation lasting >6 hours in one day, median follow-up 4.9 years (max. follow-up 8.1 years) | 
| Change in Quality of Life Measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) | The overall summary score of the Kansas City Cardiomyopathy Questionnaire will be analyzed. The KCCQ measures Quality of Life on a 0-100 scale with higher scores indicating better QoL | from baseline to 24M follow up | 
| Change in Quality of Life Measured by the EQ-5D | The EQ-5D descriptive system comprises the following five dimensions, each describing a different aspect of health: MOBILITY, SELF-CARE, USUAL ACTIVITIES, PAIN /DISCOMFORT and ANXIETY / DEPRESSION. Each dimension has three levels: no problems, some problems, extreme problems (labelled 1-3). We calculated the EQ-5D summary index by applying a specific formula providing a valuation to the health states (Shaw et al. Medical Care 2005). For the summary index, value 0 represents health that is valued as equal to death and value 1 represents best possible health. | from baseline to 24M follow up | 
| All-cause Re-admissions Within 30 Days After a Heart Failure Admission Per 100 Patient Years | All-cause hospital re-admissions within 30 days after discharge from a heart failure admission are reported as number of cases per 100 patient years | from subject randomization until study exit, median follow-up 4.9 years (max. follow-up 8.1 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AdaptivCRT, aCRT