Trial Outcomes & Findings for Safety and Efficacy Study of IPG Patient With Home Monitoring (NCT NCT01523704)

Results Overview

The purpose of the primary endpoint is to compare the composite safety endpoint, Safety Event Rate (SER) which includes death, incidence of strokes and cardiovascular related serious adverse events requiring surgical interventions (e.g. device explants or lead revision) between HM Group and Control Group. Safety will be evaluated in the following testable hypothesis in an equivalence (non-inferiority) format: HØ: The safety event rate (SER) for a 24-month duration for Group 1 is not equivalent to the SER for Group 2. SER Group 1 - SER Group 2 ≥ Ha : The safety event rate (SER) for a 12-month duration for Group 1 is equivalent to the SER for Group 2 SER Group 1 - SER Group 2 \< Where, ( )represents the allowable clinically significant difference. 5% was set for the study. A rejection of the null hypothesis (HØ) will indicate that the safety event rate for Group 1 is equivalent (non-inferior) to that of Group 2.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

1327 participants

Primary outcome timeframe

2 years

Results posted on

2021-01-27

Participant Flow

1327 patients were enrolled. At the 3-month follow-up, 53 patients were excluded (24 withdrew consent, 17 death, 8 lost to follow-up and 4 protocol deviation). 1274 patients were randomized.

Participant milestones

Participant milestones
Measure	Home Monitoring Group Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up
Overall Study STARTED	636	638
Overall Study COMPLETED	558	550
Overall Study NOT COMPLETED	78	88

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study of IPG Patient With Home Monitoring

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Home Monitoring Group n=636 Participants Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control n=638 Participants Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up	Total n=1274 Participants Total of all reporting groups
Age, Continuous	75.8 years STANDARD_DEVIATION 9.7 • n=5 Participants	77.2 years STANDARD_DEVIATION 9.7 • n=7 Participants	77 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	297 Participants n=5 Participants	345 Participants n=7 Participants	642 Participants n=5 Participants
Sex: Female, Male Male	339 Participants n=5 Participants	293 Participants n=7 Participants	632 Participants n=5 Participants
Region of Enrollment Japan	636 participants n=5 Participants	638 participants n=7 Participants	1274 participants n=5 Participants

PRIMARY outcome

Timeframe: 2 years

The purpose of the primary endpoint is to compare the composite safety endpoint, Safety Event Rate (SER) which includes death, incidence of strokes and cardiovascular related serious adverse events requiring surgical interventions (e.g. device explants or lead revision) between HM Group and Control Group. Safety will be evaluated in the following testable hypothesis in an equivalence (non-inferiority) format: HØ: The safety event rate (SER) for a 24-month duration for Group 1 is not equivalent to the SER for Group 2. SER Group 1 - SER Group 2 ≥ Ha : The safety event rate (SER) for a 12-month duration for Group 1 is equivalent to the SER for Group 2 SER Group 1 - SER Group 2 \< Where, ( )represents the allowable clinically significant difference. 5% was set for the study. A rejection of the null hypothesis (HØ) will indicate that the safety event rate for Group 1 is equivalent (non-inferior) to that of Group 2.

Outcome measures

Outcome measures
Measure	Home Monitoring Group n=558 Participants Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control n=550 Participants Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up
Evaluation for Equivalence of the Number of Patients Who Meet the Composite Safety Endpoint Between Home Monitoring Group(HM) and Control Group Which is HM + Conventional In-office Follow-up	61 Participants	65 Participants

SECONDARY outcome

Timeframe: 2 years

Population: 1134 patients were analysed, 534 from HM group and 600 from Control group. The lower number of patients from HM group can be explained by the fact that patients without any in-office FU after the 3M FU. Since HM group patients had no scheduled FUs after 3M before 27M, more patients of this group were excluded due to early drop-out.

Average numbers of outpatient follow-up(FU)s per patient are compared between Home Monitoring(HM) group and the control group, assessing total numbers of outpatient FUs combining regular and additional FUs. If the average number of visits in HM group is significantly less than that in Control group, it would serve as supporting evidence that the number of outpatient FUs can be reduced with HM. Analysis is performed on those patients that had a regular 3 months-FU following Intention to treat(ITT) principle. The analysis population of endpoint can be expected to be larger than the analysis population of the primary endpoints because patients with drop-out after the 3-months FU, but before the 27 months-FU will be included. The numbers of FU visits that occur in the 2 groups during the study period are compared as follows: AveN Group 1= Average number of FU visits per 2 years in the HM group AveN Control= Average number of FU visits per 2 years in the control group

Outcome measures

Outcome measures
Measure	Home Monitoring Group n=534 Participants Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control n=600 Participants Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up
The Median (IQR) Numbers of In-office Follow-up（FU) Visits Per Patient-year	0.69 In-office FU visits per patient per year Standard Deviation 0.43	2.00 In-office FU visits per patient per year Standard Deviation 0.40

SECONDARY outcome

Timeframe: 2 years

The sum of insured medical expenses for regular and additional outpatient FUs will be compared between HM group and Control group. It shall include Fees of FU consultation, cardiac IPG instruction, and other diagnostic test , but treatment fees including medication. Hospitalization are not included. This analysis is performed on the same ITT population as the analysis set of the first secondary endpoint. To compensate for possible asymmetric drop-out, the comparison will not be cost per patient, but costs per patient-year. Study costs per patient will be calculated by summing up all relevant variables in 3mFU Randomization CRF (points2-11) as well as in InOffice FU CRF and in Additional InOffice FU CRF. Total costs per patient result by multiplying the sum of all points by 10. Unit measurement is Yen. H : The average costs in HM group are not less than that in Control group. AveCostsHM ≥ AveCostsControl Ha: The average costs in HM group are less than that in Control group.

Outcome measures

Outcome measures
Measure	Home Monitoring Group n=635 Participants Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control n=634 Participants Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up
Efficacy of Home Monitoring：Average Cost for In-office Follow-up Per Patient-year	21065 Cost for in-office FU per patint-year Standard Deviation 23051	23552 Cost for in-office FU per patint-year Standard Deviation 23986

Adverse Events

Home Monitoring Group

Serious events: 68 serious events

Other events: 7 other events

Deaths: 46 deaths

Control

Serious events: 68 serious events

Other events: 16 other events

Deaths: 41 deaths

Serious adverse events

Serious adverse events
Measure	Home Monitoring Group n=558 participants at risk Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control n=550 participants at risk Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up
Cardiac disorders The number of the composite primary endpoint	10.9% 61/558 • Number of events 68 • 24 months	11.8% 65/550 • Number of events 68 • 24 months
Vascular disorders The number of Stroke	1.4% 8/558 • Number of events 8 • 24 months	1.3% 7/550 • Number of events 7 • 24 months
Cardiac disorders The number of Cardiovascular surgery	2.5% 14/558 • Number of events 14 • 24 months	3.6% 20/550 • Number of events 20 • 24 months
Cardiac disorders Death	8.2% 46/558 • Number of events 46 • 24 months	7.5% 41/550 • Number of events 41 • 24 months

Other adverse events

Other adverse events
Measure	Home Monitoring Group n=558 participants at risk Patients assigned to HM Group(HM follow-up ONLY) will have Home Monitoring programmed ON. They will be seen in the office for device interrogations at the 3-month follow-up, and at 27 month follow-up. In the meanwhile the device status will be evaluated using HM only for the 9, 15 and 21 month scheduled follow-up. Patients will visit the hospital for device interrogation on 27 month final follow-up. BIOTRONIK Home Monitoring System: Home Monitoring system transfers implantable device's data to the main server via internet.	Control n=550 participants at risk Patients assigned to Control Group (HM + Conventional In-office follow-up - Control group) will have HM programmed ON. In addition to HM, these patients will visit the hospital for device interrogation at 3, 9, 15, 21 and 27 month follow-ups. BIOTRONIK Home Monitoring System with In-office Follow-up
Cardiac disorders Other safety events	1.3% 7/558 • Number of events 7 • 24 months	2.9% 16/550 • Number of events 16 • 24 months

Additional Information

Eiichi Watanabe, MD, PhD

Fujita Health University School of Medicine

Phone: +81-562-93-2312

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60