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

Terminated

Phase 4 Results

Trial Description

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

Conditions

Interventions

  • Oral Anticoagulation (dabigatran etexilate, warfarin) Drug
    Intervention Desc: Patients will receive physician-directed anticoagulation therapy based on conventional criteria.
    ARM 1: Kind: Experimental
    Label: 1
    Description: Patients randomized to Group 1 (Intervention arm) have HM fully enabled and continuous remote surveillance data is available to clinicians. The investigators actively monitor for atrial episodes through the automatic HM notifications (email, fax, short message service). The total duration of AF/AFL combined with patients' CHADS2 score determines the start, stop, and restart of OAC. 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. Based on active HM alerts, the cycle may repeat indefinitely.
    ARM 2: Kind: Experimental
    Label: 2
    Description: Patients assigned to Group 2 (Control arm) have HM active (BIOTRONIK Safety Net), 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.
  • Oral Anticoagulation Drug
    Intervention Desc: Patients will receive physician-directed anticoagulation therapy based on conventional criteria. OAC drugs used: Dabigatran etexilate, Rivaroxaban, Warfarin
    ARM 1: Kind: Experimental
    Label: Intervention (Group 1)
    Description: Home Monitoring is fully enabled and continuous remote surveillance data is available to investigators. Patients will be treated according to a predefined anticoagulation plan. The total duration of AF/AFL combined with patients' CHADS2 score determines the start, stop, and restart of OAC. Based on active HM alerts, the OAC cycle may repeat indefinitely.
    ARM 2: Kind: Experimental
    Label: Control (Group 2)
    Description: 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 Drug
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: Home Monitoring Guided OAC
    Description: 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.
  • Physician-Directed OAC Drug
    Intervention Desc: Patients will receive physician-directed anticoagulation therapy based on conventional criteria. OAC drugs used: Dabigatran etexilate, Rivaroxaban, Warfarin, other approved VKA
    ARM 1: Kind: Experimental
    Label: Physician-Directed OAC
    Description: 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

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Investigator)
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary The study hypothesis states that early detection of AF/AFL based on BIOTRONIK HM technology combined with a predefined anticoagulation plan will reduce the rate of the composite endpoint of stroke, systemic embolism and major bleeding. 3 years No
Secondary Rates of all-cause mortality, stroke (ischemic and hemorrhagic, disabling and non-disabling, cardioembolic and non-cardioembolic), and major bleeding, as well as the AF burden, quality of life, and mean heart rate reduction. 3 years No
Primary Composite Primary Endpoint: Time to First 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 No
Primary 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 No
Secondary Rates of All-cause Mortality Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years
Secondary 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
Secondary 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
Secondary Rate of Major Bleeding Events Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years
Secondary 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
Secondary 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
Secondary Change in Quality of Life Score 1 year
Secondary Mean Ventricular Heart Rate Reduction 1 year

Sponsors