Trial Outcomes & Findings for Combined Use of BIOTRONIK Home Monitoring and Predefined Anticoagulation to Reduce Stroke Risk (NCT NCT00559988)

NCT ID: NCT00559988

Last Updated: 2017-12-05

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 2718 participants
• Primary outcome timeframe: From date of enrollment until date of primary endpoint event, assessed up to study exit, with a mean treatment duration of 2.0 years
• Results posted on: 2017-12-05

Participant Flow

Participant milestones

Measure	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 oral anticoagulation therapy.	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 oral anticoagulation therapy consistent with current standards of care.
Overall Study STARTED	1357	1361
Overall Study COMPLETED	1006	1009
Overall Study NOT COMPLETED	351	352

Reasons for withdrawal

Measure	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 oral anticoagulation therapy.	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 oral anticoagulation therapy consistent with current standards of care.
Overall Study Death	147	140
Overall Study Withdrawal by Subject	152	139
Overall Study Lost to Follow-up	42	56
Overall Study ICD device explanted	10	17

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.	Total n=2718 Participants Total of all reporting groups
Age, Continuous	64.7 years STANDARD_DEVIATION 10.8 • n=5 Participants	64.2 years STANDARD_DEVIATION 11.5 • n=7 Participants	64.4 years STANDARD_DEVIATION 11.2 • n=5 Participants
Sex: Female, Male Female	347 Participants n=5 Participants	368 Participants n=7 Participants	715 Participants n=5 Participants
Sex: Female, Male Male	1010 Participants n=5 Participants	993 Participants n=7 Participants	2003 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of enrollment until date of primary endpoint event, assessed up to study exit, with a mean treatment duration of 2.0 years

Population: Intent to treat analysis of all enrolled subjects

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.

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed Kaplan-Meier estimate at 1 Year	97.5 percentage of participants-Kaplan Meier	97.7 percentage of participants-Kaplan Meier
Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed Kaplan-Meier estimate at 2 Years	94.8 percentage of participants-Kaplan Meier	95.7 percentage of participants-Kaplan Meier
Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed Kaplan-Meier estimate at 3 Years	92.3 percentage of participants-Kaplan Meier	92.0 percentage of participants-Kaplan Meier
Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed Kaplan-Meier estimate at 4 Years	90.0 percentage of participants-Kaplan Meier	89.4 percentage of participants-Kaplan Meier
Composite Primary Endpoint: Kaplan-Meier Estimate of Patients Without a Stroke, Systemic Embolism, or Major Bleed Kaplan-Meier estimate at 5 Years	86.8 percentage of participants-Kaplan Meier	87.9 percentage of participants-Kaplan Meier

SECONDARY outcome

Timeframe: Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Rates of All-cause Mortality	147 Participants	140 Participants

SECONDARY outcome

Timeframe: Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Rate of Ischemic and Hemorrhagic Stroke Ischemic stroke	22 Participants	28 Participants
Rate of Ischemic and Hemorrhagic Stroke Hemorrhagic stroke	3 Participants	3 Participants

SECONDARY outcome

Timeframe: Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Rate of Fatal or Disabling and Non-disabling Stroke Fatal or disabling stroke	9 Participants	11 Participants
Rate of Fatal or Disabling and Non-disabling Stroke Non-disabling stroke	15 Participants	19 Participants

SECONDARY outcome

Timeframe: Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Rate of Major Bleeding Events	46 Participants	34 Participants

SECONDARY outcome

Timeframe: Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Mean Atrial Fibrillation/Atrial Flutter Burden	1.3 percent daily burden Standard Deviation 8.2	1.2 percent daily burden Standard Deviation 7.4

SECONDARY outcome

Timeframe: Study duration from date of enrollment to date of study exit, with mean implant duration of 2.0 years

Outcome measures

Measure	Home Monitoring Guided OAC n=1357 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Rate of Cardioembolic and Non-cardioembolic Stroke Cardiogenic embolism	9 Participants	7 Participants
Rate of Cardioembolic and Non-cardioembolic Stroke Non-cardiogenic	5 Participants	8 Participants

SECONDARY outcome

Timeframe: 1 year

Population: Subjects with paired baseline and 1 year Quality of Life scores

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.

Outcome measures

Measure	Home Monitoring Guided OAC n=886 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=889 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Change in Quality of Life Score Physical health summary	1.3 Scores on a scale Standard Deviation 8.8	0.9 Scores on a scale Standard Deviation 8.8
Change in Quality of Life Score Mental health summary	1.9 Scores on a scale Standard Deviation 11.0	1.6 Scores on a scale Standard Deviation 11.2

SECONDARY outcome

Timeframe: 1 year

Population: Subjects with baseline and 1 year ventricular rate information

Outcome measures

Measure	Home Monitoring Guided OAC n=877 Participants 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 oral anticoagulation therapy.	Physician-Directed OAC n=878 Participants 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 oral anticoagulation therapy consistent with current standards of care.
Mean Ventricular Heart Rate Reduction	0.07 beats per minute Standard Deviation 6.31	-0.34 beats per minute Standard Deviation 5.90

Adverse Events

Home Monitoring Guided OAC

Serious events: 372 serious events

Other events: 135 other events

Deaths: 0 deaths

Physician-Directed OAC

Serious events: 374 serious events

Other events: 139 other events

Deaths: 0 deaths

Serious adverse events

Measure	Home Monitoring Guided OAC n=1357 participants at risk 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 participants at risk 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 oral anticoagulation therapy consistent with current standards of care.
Cardiac disorders Congestive heart failure	10.0% 136/1357 • Number of events 229 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	9.3% 127/1361 • Number of events 222 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Arrhythmia	4.7% 64/1357 • Number of events 81 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	4.6% 63/1361 • Number of events 77 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Angina	3.1% 42/1357 • Number of events 60 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	3.9% 53/1361 • Number of events 65 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Dyspnea	1.3% 17/1357 • Number of events 20 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	1.9% 26/1361 • Number of events 26 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Coronary artery disease	2.1% 28/1357 • Number of events 31 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	1.3% 18/1361 • Number of events 21 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Myocardial infaction	1.9% 26/1357 • Number of events 30 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	2.6% 35/1361 • Number of events 39 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Cardiac arrest	1.7% 23/1357 • Number of events 24 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	2.0% 27/1361 • Number of events 27 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Nervous system disorders Stroke	1.6% 22/1357 • Number of events 25 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	2.2% 30/1361 • Number of events 31 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Vascular disorders Gastrointestianal bleeding	1.7% 23/1357 • Number of events 25 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	1.3% 18/1361 • Number of events 19 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Surgical and medical procedures Upgrade to CRT-D device	1.8% 25/1357 • Number of events 26 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	1.3% 18/1361 • Number of events 18 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Surgical and medical procedures Device replacement	1.1% 15/1357 • Number of events 15 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	0.66% 9/1361 • Number of events 9 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Surgical and medical procedures Lead replacement or repositioning	1.2% 16/1357 • Number of events 17 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	0.81% 11/1361 • Number of events 12 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.

Other adverse events

Measure	Home Monitoring Guided OAC n=1357 participants at risk 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 oral anticoagulation therapy.	Physician-Directed OAC n=1361 participants at risk 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 oral anticoagulation therapy consistent with current standards of care.
Cardiac disorders Congestive Heart Failure	1.6% 22/1357 • Number of events 39 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	1.8% 25/1361 • Number of events 51 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Arrhythmia	3.8% 52/1357 • Number of events 84 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	3.9% 53/1361 • Number of events 74 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Angina	2.4% 32/1357 • Number of events 49 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	2.5% 34/1361 • Number of events 48 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Cardiac disorders Dyspnea	1.4% 19/1357 • Number of events 19 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	1.3% 18/1361 • Number of events 19 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.
Surgical and medical procedures Device replacement	2.1% 29/1357 • Number of events 29 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.	2.6% 35/1361 • Number of events 35 • Study duration from date of enrollment to date of study exit, with a mean implant duration of 2.0 years Data for serious adverse event subcategories with an incidence of less than 1.0% are not shown. Patients could have more than one event.

Additional Information

Crystal Miller

Biotronik, Inc

Phone: 503-451-8051

Email: crystal.miller@biotronik.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place