BIO|Adapt: Evaluation of the BIOTRONIK AutoAdapt Algorithm for Continuous Automatic Adaptive Cardiac Resynchronization

Sponsor

Biotronik SE & Co. KG (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04774523

Collaborator

(none)

350

Enrollment

Location

Arms

Anticipated Duration (Months)

10.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

BIO|Adapt study is designed to provide evidence for the clinical benefit of the CRT AutoAdapt feature. This feature provides continuous adaptation of AV delay and biventricular pacing modality. However, additional clinical data on the short and mid-term improvement of CRT-D patients by the CRT AutoAdapt feature are needed.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Cardiac Arrhythmia Left Ventricular Dysfunction	Procedure: Echo-based assessment of the acute hemodynamic effect of the CRT AutoAdapt feature. Procedure: Echocardiography AV optimization Procedure: Echocardiography Other: Self Assessment Score	N/A

Detailed Description

The magnitude of clinical and hemodynamic benefit of CRT varies significantly among its recipients. Many studies report that approximately one-third of the implanted population show no clinical improvement at follow-ups. There are many clinical factors that are associated with the CRT response and the grade of benefit, such as type of cardiomyopathy, severity of electrical conduction abnormalities, dyssynchrony, and scar burden. In addition, there are device-related factors such as lead location, insufficient ventricular pacing percentage (%V), and suboptimal atrial-ventricular (AV) and ventricle- ventricle (VV) timing.

The main finding in such CRT non-responders is a suboptimal AV-timing (47%). The optimization of AV and VV intervals during biventricular (BiV) pacing is an option to maximize the positive effects of CRT, by taking advantage of the full atrial contraction for optimal filling of the ventricles. Optimization is usually accomplished by using echocardiography or other methods. However, such methods are time consuming for the hospitals and may not provide a benefit for every patient.

The most common pacing mode for CRT therapy is BiV pacing, but many acute and chronic randomized clinical studies have demonstrated that left-ventricular (LV) pacing can be at least as effective as BiV pacing. In patients with sinus rhythm and normal atrioventricular (AV) conduction, pacing the left ventricle only with an appropriate AV interval can result in an even superior LV and right ventricular (RV) function compared with standard BiV pacing. LV pacing has been proposed as an alternative approach to apply cardiac resynchronization as it has been shown that LV pacing induces short-term hemodynamic benefits compared to BiV pacing.

Different algorithms have been developed by different manufactures to provide continuous automatic CRT optimization, allowing a more physiologic ventricular activation and greater device longevity in patients with normal AV conduction due to the reduction of unnecessary RV pacing. Studies with the Medtronic Adaptive cardiac resynchronization therapy (aCRT) algorithm, that provides automatic ambulatory selection between synchronized LV or BiV pacing with dynamic optimization of atrioventricular and interventricular delays, have shown that the algorithm is safe and as effective as BiV pacing with comprehensive echocardiographic optimization.

The CRT AutoAdapt feature by BIOTRONIK optimizes the CRT therapy settings of the device automatically and continuously. This algorithm adjusts the AV delay and sets the ventricular pacing configuration to BiV or LV. The settings are based on intracardiac conduction times, which are measured every 60 seconds to select the optimal configuration.

The objective of this study is to show non-inferiority of this feature compared to standard echo-based optimization with regard to clinical benefit.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

350 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

There will be two arms with the same study flow chart along the study.There will be two arms with the same study flow chart along the study.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of the BIOTRONIK AutoAdapt Algorithm for Continuous Automatic Adaptive Cardiac Resynchronization

Actual Study Start Date :

Aug 31, 2021

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control group This group will be made up of patients implanted with CRT-D devices without the availability of the CRT AutoAdapt feature.	Procedure: Echocardiography AV optimization Patient in the control group undergo the routine echo based AV-optimization that is usually performed at the investigational site (Ritter method23 or iterative method23). Performance of an additional VV-delay optimization is left to the investigators discretion Procedure: Echocardiography Echocardiography must be performed at baseline and 12 month Follow Up to collect the LVEF/LVESD(V)/LVEDD(V) Other: Self Assessment Score Patient must complete the self assessment score at 6 and 12 month Follow Up, that will be use for the Packer Clinical Composite Score
Experimental: AutoAdapt group This group will be made up of patients implanted with CRT-D devices that have the CRT AutoAdapt feature available. It is mandatory that all patients within this group have the feature activated, independently of other characteristics.	Procedure: Echo-based assessment of the acute hemodynamic effect of the CRT AutoAdapt feature. Patients in the AutoAdapt group undergo the echo-based assessment of the acute hemodynamic effect of the CRT AutoAdapt feature. Three steps must be followed: Standard AV programming: perform echo for AoVTI assessment. Echo-optimized AV programming: perform standard echo-based AV-optimization (Ritter method or iterative method, according to routine at investigational site); measure AoVTI at optimized setting. AutoAdapt optimized programming: The system allows different programming options for the parameter 'Adaptive AV reduction'. The nominal value is 0.7, but it can be modified to different values ranging from 0.5 to 0.9. The AoVTI shall be measured at three settings of the "Adaptive Av reduction" parameter: at standard setting, at 0.5 and at 0.9. Procedure: Echocardiography Echocardiography must be performed at baseline and 12 month Follow Up to collect the LVEF/LVESD(V)/LVEDD(V) Other: Self Assessment Score Patient must complete the self assessment score at 6 and 12 month Follow Up, that will be use for the Packer Clinical Composite Score

Arm

Intervention/Treatment

Active Comparator: Control group

This group will be made up of patients implanted with CRT-D devices without the availability of the CRT AutoAdapt feature.

Procedure: Echocardiography AV optimization

Patient in the control group undergo the routine echo based AV-optimization that is usually performed at the investigational site (Ritter method23 or iterative method23). Performance of an additional VV-delay optimization is left to the investigators discretion

Procedure: Echocardiography

Echocardiography must be performed at baseline and 12 month Follow Up to collect the LVEF/LVESD(V)/LVEDD(V)

Other: Self Assessment Score

Patient must complete the self assessment score at 6 and 12 month Follow Up, that will be use for the Packer Clinical Composite Score

Experimental: AutoAdapt group

This group will be made up of patients implanted with CRT-D devices that have the CRT AutoAdapt feature available. It is mandatory that all patients within this group have the feature activated, independently of other characteristics.

Procedure: Echo-based assessment of the acute hemodynamic effect of the CRT AutoAdapt feature.

Patients in the AutoAdapt group undergo the echo-based assessment of the acute hemodynamic effect of the CRT AutoAdapt feature. Three steps must be followed: Standard AV programming: perform echo for AoVTI assessment. Echo-optimized AV programming: perform standard echo-based AV-optimization (Ritter method or iterative method, according to routine at investigational site); measure AoVTI at optimized setting. AutoAdapt optimized programming: The system allows different programming options for the parameter 'Adaptive AV reduction'. The nominal value is 0.7, but it can be modified to different values ranging from 0.5 to 0.9. The AoVTI shall be measured at three settings of the "Adaptive Av reduction" parameter: at standard setting, at 0.5 and at 0.9.

Procedure: Echocardiography

Echocardiography must be performed at baseline and 12 month Follow Up to collect the LVEF/LVESD(V)/LVEDD(V)

Other: Self Assessment Score

Patient must complete the self assessment score at 6 and 12 month Follow Up, that will be use for the Packer Clinical Composite Score

Outcome Measures

Primary Outcome Measures

CRT-responder rate based on improvement in Clinical Composite Score developed by Packer at 12 month follow up. [12 month Follow Up]
It will be use Packer Score to assess the clinical outcome in heart failure patients. It takes into account all possible dimensions of outcome, i.e. mortality, morbidity and quality of life and is based on the following data points: Death (yes/no) Any unplanned hospitalization for worsening heart failure (yes/no) Change in NYHA class compared to baseline (improved/unchanged/worsened) Patient's global assessment (PGA) compared to baseline (improved - three stages / unchanged / worsened - three stages) Discontinuation of study protocol due to worsening heart failure, treatment failure or lacking therapeutic response (yes/no) At the end of the study, the outcome of each patient is classified as: Worsened Unchanged Improved

Secondary Outcome Measures

Acute hemodynamic effect of AutoAdapt feature [At pre-hospital discharge assessed up to 30 days since the implantation]
The acute hemodynamic response to different parameter settings will be assessed by measuring the aortic velocity time integral (AoVTI) via echocardiography.
Change in LVEF [12 month Follow Up]
The intra-individual change in LVEF from baseline to 12 month FU will be assessed by echocardiography as a measure of improvement in cardiac function and compared between patient groups.
Change in Left Ventricular End Diastolic and Systolic Diameter (LVED(S)D) [12 month Follow Up]
The intra-individual change in LVED(S)D from baseline to 12 month FU will be assessed by echocardiography as a measure of ventricular reverse remodeling and compared between patient groups.
Change in Left Ventricular End Diastolic and Systolic Volumes (LVED(S)V) [12 month Follow Up]
The intra-individual change in LVED(S)V from baseline to 12 month FU will be assessed by echocardiography as a measure of ventricular reverse remodeling and compared between patient groups.
Change in NYHA class [12 month Follow Up]
The intra-individual change in the NYHA classification from baseline to 12 months will be assessed as a measure of overall functional improvement and compared between patient groups.
Percentage of LV only pacing [12 month Follow Up]
The percentage of LV only pacing based on device statistics will be assessed at the 12 months FU and compared between patient groups to assess the potential to reduce battery consumption by the AutoAdapt feature.
Adverse device effects related to the CRT AutoAdapt feature [12 month Follow Up]
Evaluation of all reported adverse device effects for a possible relation with the CRT AutoAdapt feature

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Indication for de novo implantation or upgrade to a CRT-D device
Enrolled in BIO|STREAM.HF but not yet implanted with or upgraded to CRT-D
LVEF < 35%
QRS > 120 ms
NYHA II-IV
Atrial heart rate during sinus rhythm at rest below 100 bpm
Patient is able to understand the nature of the study and willing to provide written informed consent to this submodule