Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk

Study Overview
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Brief Summary
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The IMPACT Study will investigate the potential clinical benefit of the combined use of BIOTRONIK Home Monitoring (HM) technology and a predefined anticoagulation plan compared to conventional device evaluation and physician-directed anticoagulation in patients with implanted dual-chamber defibrillators or cardiac resynchronization therapy devices.

Detailed Description
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Atrial fibrillation (AF) and atrial flutter (AFL) are common cardiac arrhythmias associated with an increased incidence of stroke in patients with additional risk factors. Oral Anticoagulation (OAC) reduces stroke risk, but because these arrhythmias are frequently intermittent and asymptomatic, start of OAC therapy is often delayed until electrocardiographic documentation is obtained. Technological advances in implanted dual-chamber cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D) devices allow early detection and real time verification of AF/AFL with intracardiac electrograms (IEGM) automatically transmitted to the clinicians. Such remote diagnostic capability might be particularly relevant in patients with asymptomatic AF by allowing timely treatment. Compared to conventional periodic, (e.g., quarterly) office device evaluation, daily remote monitoring may prove superior for diagnosis of AF and prophylactic treatment of thromboembolism. The start, stop and restart of OAC based on a predefined atrial rhythm-guided strategy in conjunction with a standard risk-stratification scheme could lead to better clinical outcomes compared with conventional clinical care. The study is designed to demonstrate a risk reduction of both thromboembolism proximate to episodes of documented AF/AFL and bleeding potentiated by chronic OAC in the absence of AF. Verification of this premise would impact the clinical practice, providing evidence to physicians for the use of HM to guide OAC in patients with AF/AFL. The results of this study should demonstrate the clinical value of wireless remote surveillance of the cardiac rhythm and may define the critical threshold of AF/AFL burden warranting OAC or antiarrhythmic drug therapy in patients at risk of stroke

Official Title
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The IMPACT of BIOTRONIK Home Monitoring Guided Anticoagulation on Stroke Risk in Patients With ICD and CRT-D Devices

Conditions
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Atrial Flutter, Atrial Fibrillation, Stroke, Embolism, Systemic Arterial, Major Bleeding

Intervention / Treatment
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* Drug: Home Monitoring Guided OAC
* Drug: Physician-Directed OAC


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Candidates for implantation of, or already implanted with, a BIOTRONIK Lumax HF-T or DR-T device Documented P wave mean amplitude ≥ 1.0 mV (sinus rhythm) or ≥ 0.5 mV (AF) at enrollment, if previously implanted CHADS2 risk score ≥ 1 Able and willing to follow OAC therapy if the indication develops during the course of the trial Able to utilize the HM throughout the study Key Exclusion Criteria: Permanent AF History of stroke, transient ischemic attack (TIA) or systemic embolism and documented AF or AFL Currently requiring OAC therapy for any indication Patients who underwent successful AF ablation (sinus rhythm restored) and have not completed a minimum of 3 months of OAC therapy Known, current contraindication to use of eligible OAC Long QT or Brugada syndrome as the sole indication for device implantation Life expectancy less than the expected term of the study

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Home Monitoring Guided OAC<br>Home Monitoring is fully enabled and continuous remote surveillance data is available to investigators. Patients will be treated according to a predefined anticoagulation plan, which uses the total duration of AF/AFL combined with patients' CHADS2 score to determine the start, stop, and restart of OAC. | Drug: Home Monitoring Guided OAC<br>* Active monitoring for atrial episodes through the automatic HM notifications (email, fax, short message service) is required. If the total duration over 48 consecutive hours reaches the predefined anticoagulation condition, and AF/AFL diagnosis is confirmed using the IEGM online, the site instructs the patient by telephone to start OAC. Clinicians continue to monitor patients using HM, and if freedom from AF/AFL reaches the predefined interval, stop of OAC therapy is requested over the telephone. Following stop of anticoagulation, any recurrence of AF/AFL requires restart of OAC therapy. OAC drugs used: Dabigatran etexilate, Rivaroxaban, Warfarin, other approved VKA<br>|
| Active Comparator: Physician-Directed OAC<br>In Control (Group 2), Home Monitoring is active for Safety Net alerts, but the remote AF/AFL data is not revealed to the patient or treating physician. These patients receive physician-directed OAC consistent with current standards of care. Safety Net data include: ERI/EOS Special Implant Status Implant in Backup Mode (ROM) VT/ VF Detection Inactive Emergency Pacing 250 Ω > RV Pacing Impedance > 1500 Ω Symptomatic VT/VF therapies including both ATP and shock VT/VF storm HM transmission failure >3 days | Drug: Physician-Directed OAC<br>* Patients will receive physician-directed anticoagulation therapy based on conventional criteria. OAC drugs used: Dabigatran etexilate, Rivaroxaban, Warfarin, other approved VKA<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed | The primary endpoint is to demonstrate whether early detection of atrial arrhythmias based on BIOTRONIK Home Monitoring technology combined with a predefined anticoagulation plan in the Home Monitoring Guided OAC group is superior to the Physician-Directed OAC group reflecting conventional care and physician directed treatment of AF in terms of risk reduction of the primary composite endpoint including stroke, systemic embolism, and major bleeding events. | From date of enrollment until date of primary endpoint event, assessed up to study exit, with a mean treatment duration of 2.0 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of All-cause Mortality |  | Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years | 
| Rate of Ischemic and Hemorrhagic Stroke |  | Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years | 
| Rate of Fatal or Disabling and Non-disabling Stroke |  | Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years | 
| Rate of Major Bleeding Events |  | Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years | 
| Mean Atrial Fibrillation/Atrial Flutter Burden |  | Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years | 
| Rate of Cardioembolic and Non-cardioembolic Stroke |  | Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years | 
| Change in Quality of Life Score | Quality of Life was evaluated using the SF-36 v2 Health Survey. The SF-36 consists of eight scaled scores which correspond to the following sections: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, and mental health. Responses are recoded per a scoring key with each question having a value from 0 to 100. Scores from items in the same scale are averaged together per the scoring key to create the section and subsection (physical health and mental health) scores. For all reported scores, the lowest possible value is 0 (representing the highest disability) and the highest possible value is 100 (representing no disability). Therefore, a positive change from baseline to 1 year represents an improvement in disability, while a negative change represents a worsening of disability. | 1 year | 
| Mean Ventricular Heart Rate Reduction |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Implanted Cardioverter Defibrillator, Cardiac Resynchronization Therapy Defibrillator, Home Monitoring, Oral Anticoagulation