Bradyarrhythmia
Conditions
Brief summary
The number of patients with implantable pulse generator (IPG) has steadily increased in Japan causing increment in number of in office follow-ups and greater burden on many hospitals. The purpose of this multicenter randomized study is to demonstrate that BIOTRONIK Home Monitoring system reduces office follow-up visits without compromising patient safety.
Detailed description
Patients will be randomized into HM follow-up only (Group 1) or HM & in-office follow-up (Group 2) and will be followed-up for 27 months.
Interventions
DEVICEBIOTRONIK Home Monitoring System
Home Monitoring system transfers implantable device's data to the main server via internet.
DEVICEBIOTRONIK Home Monitoring System with In-office Follow-up
Sponsors
Biotronik Japan, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Indicated for IPG implantation under Japanese guidelines * Implanted within the last 45 days or being considered for implant with a BIOTRONIK IPG with Home Monitoring * Able to utilize HM system throughout the study * Ability to give informed consent * Geographically stable and able to return for follow-ups for 27 months * Over 20 years old * Patient able to understand and follow the procedure stated in protocol
Exclusion criteria
* Contraindicated for IPG under Japanese guidelines * Patients who are currently included in another cardiac clinical study * Patients with expected life period of less than two years * Patients who might undergo heart transplantation in next two years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Median (IQR) Numbers of In-office Follow-up（FU) Visits Per Patient-year | 2 years | 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 |
| Efficacy of Home Monitoring：Average Cost for In-office Follow-up Per Patient-year | 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. |
Countries
Japan
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 636 |
| 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 | 638 |
| Total | 1,274 |
Baseline characteristics
| Characteristic | Home Monitoring Group | Control | Total |
|---|---|---|---|
| Age, Continuous | 75.8 years STANDARD_DEVIATION 9.7 | 77.2 years STANDARD_DEVIATION 9.7 | 77 years STANDARD_DEVIATION 10 |
| Region of Enrollment Japan | 636 participants | 638 participants | 1274 participants |
| Sex: Female, Male Female | 297 Participants | 345 Participants | 642 Participants |
| Sex: Female, Male Male | 339 Participants | 293 Participants | 632 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 46 / 558 | 41 / 550 |
| other Total, other adverse events | 7 / 558 | 16 / 550 |
| serious Total, serious adverse events | 68 / 558 | 68 / 550 |
Outcome results
Primary
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
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Home Monitoring Group | 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 |
| Control | 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 | 65 Participants |
Secondary
Efficacy of Home Monitoring：Average Cost for In-office Follow-up Per Patient-year
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.
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Home Monitoring Group | 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 |
| Control | Efficacy of Home Monitoring：Average Cost for In-office Follow-up Per Patient-year | 23552 Cost for in-office FU per patint-year | Standard Deviation 23986 |
Secondary
The Median (IQR) Numbers of In-office Follow-up（FU) Visits Per Patient-year
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
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Home Monitoring Group | 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 |
| Control | The Median (IQR) Numbers of In-office Follow-up（FU) Visits Per Patient-year | 2.00 In-office FU visits per patient per year | Standard Deviation 0.4 |