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

Phase 4

Terminated

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

Interventions: Drug: Physician-Directed OAC
Drug: Home Monitoring Guided OAC

Registration Number: NCT00559988

Lead Sponsor: Biotronik, Inc.

Brief Summary: 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: 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

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 2718

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Physician-Directed OAC	Physician-Directed OAC	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
Home Monitoring Guided OAC	Home Monitoring Guided OAC	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.

Primary Outcome Measures

Name	Time	Method
Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed	From date of enrollment until date of primary endpoint event, assessed up to study exit, with a mean treatment duration of 2.0 years	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.

Secondary Outcome Measures

Name	Time	Method
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 Major Bleeding Events	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	1 year	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.
Mean Ventricular Heart Rate Reduction	1 year
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
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