Bradycardia, Cardiac Pacemaker, Artificial, Cardiac Rhythm Disorder
Conditions
Keywords
Bradycardia, Sick Sinus Syndrome, Pacemaker, AV Block, Vasovagal Syncope
Brief summary
Prospective, non-randomized, multi-center, international study designed to evaluate the safety and effectiveness of the Aveir™ Dual-Chamber (DR) Leadless Pacemaker system.
Detailed description
The purpose of this clinical investigation is to evaluate the clinical safety and effectiveness of the Aveir DR Leadless Pacemaker system in a patient population indicated for a DDD(R) pacemaker. Subjects participating in the study are followed through at least 12 months with data collected at baseline, implant procedure, pre (hospital) discharge, and follow-up at 1 month, 3 months, 6 months, 12 months, and every 6 months thereafter until study completion
Interventions
Patients will undergo a dual chamber leadless pacemaker system implant wherein a leadless pacemaker will be implanted in the right ventricle and right atrium
Sponsors
Abbott Medical Devices
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, multi-center, international, single-arm, pivotal investigational study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must have at least one of the clinical indications before device implant in adherence with ACC/AHA/HRS/ESC dual chamber pacing guidelines 2. Subject is ≥ 18 years of age or age of legal consent, whichever age is greater 3. Subject has a life expectancy of at least one year 4. Subject is willing to comply with clinical investigation procedures and agrees to return to clinic for all required follow-up visits, tests, and exams 5. Subject has been informed of the nature of the clinical investigation, agrees to its provisions and has provided a signed written informed consent, approved by the IRB/EC
Exclusion criteria
1. Subject is currently participating in another clinical investigation that may confound the results of this study as determined by the Sponsor 2. Subject is pregnant or nursing and those who plan pregnancy during the clinical investigation follow-up period 3. Subject has presence of anatomic or comorbid conditions, or other medical, social, or psychological conditions that, in the investigator's opinion, could confound the assessment of the investigational device and/or implant procedure, limit the subject's ability to participate in the clinical investigation or to comply with follow-up requirements of the clinical investigation results 4. Subject has a known allergy or hypersensitivity to \< 1 mg of dexamethasone sodium phosphate or any blood or tissue contacting material listed in the IFU 5. Subject has an implanted vena cava filter or mechanical tricuspid valve prosthesis 6. Subject has pre-existing, permanent endocardial pacing or defibrillation leads (does not include lead fragments) 7. Subject has current implantation of either conventional or subcutaneous implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT) device 8. Subject has an implanted leadless cardiac pacemaker (except for an Aveir ventricular leadless pacemaker) 9. Subject is implanted with an electrically-active implantable medical device with stimulation capabilities (such as neurological or cardiac stimulators) 10. Subject is unable to read or write
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Free From Aveir DR System-Related Complications at 3-months | 3 months | Aveir DR Leadless Pacemaker system complication-free-rate in de novo subjects. A complication was defined as a device-or-procedure-related serious adverse event. Complications included Atrial LP, Ventricular LP, and implant procedure-related complications. Complications possibly related or related to COVID-19 were excluded. |
| Percentage of Participants Free From Aveir DR System-Related Complications at 12-months | 12 months | Aveir DR Leadless Pacemaker system complication-free-rate in de novo subjects. A complication was defined as a device-or-procedure-related serious adverse event. Complications included Atrial LP, Ventricular LP, and implant procedure-related complications. Complications possibly related or related to COVID-19 were excluded. |
| Percentage of Subjects With Acceptable Atrial Threshold and Amplitude Measurements at 3-months | 3 months | Composite success rate of acceptable atrial pacing thresholds and P-wave amplitudes in de novo subjects. A subject was considered to have met the primary effectiveness endpoint #1 if the pacing threshold voltage was ≤ 3.0 V at 0.4 ms at the 3-month visit and the sensed P-wave amplitude was ≥ 1.0 mV at the 3-month visit. |
| Percentage of Subjects With Acceptable Atrial Threshold and Amplitude Measurements at 12-months | 12 months | Composite success rate of acceptable atrial pacing thresholds and P-wave amplitudes in de novo subjects. A subject was considered to have met the success criteria for the endpoint if the pacing threshold voltage was ≤ 3.0 V at 0.4 ms at the 12-month visit and the sensed P-wave amplitude was ≥ 1.0 mV at the 12-month visit. |
| Percentage of Participants With AV Synchrony Success Rate at Rest While Seated | 3 months | AV synchrony success was defined as subjects with a paced or sensed ventricular beat within 300 ms following a paced or sensed atrial beat (i.e., a synchronous cycle) for at least 70% of evaluable cardiac cycles. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Free From Aveir Atrial Leadless Pacemaker-Related Complications at 3-months | 3 months | The secondary safety endpoint evaluated a 3-month Atrial LP related complication-free rate based on CEC adjudication of adverse events. An Atrial LP complication was defined as an atrial device-or-procedure-related serious adverse event. Complications that were exclusively related to the Ventricular LP or its delivery/retrieval were not considered Atrial LP complications and were excluded from the evaluation. For a conservative approach, complications that could not exclusively be determined to be related to the ventricular or Atrial LP were still considered Atrial LP complications. For example, procedure-related femoral access complications were adjudicated as Atrial LP complications. |
| Percentage of Participants Free From Aveir Atrial Leadless Pacemaker-Related Complications at 12-months | 12 months | The secondary safety endpoint analysis evaluated the 12-month Atrial LP related complication-free rate (CFRA) based on CEC adjudication of adverse events. An Atrial LP complication was defined as an atrial device-or-procedure-related serious adverse event. Complications that were exclusively related to the Ventricular LP or its delivery/retrieval were not considered Atrial LP complications and were excluded from the evaluation. For a conservative approach, complications that could not exclusively be determined to be related to the ventricular or Atrial LP were still considered Atrial LP complications. For example, procedure-related femoral access complications were adjudicated as Atrial LP complications. Complications possibly related or related to COVID-19 were excluded. |
| Slope of the Normalized Increase in the Sensor Indicated Rate Versus Normalized Workload of the Aveir Atrial Leadless Pacemaker During Exercise Testing | 3 months | Appropriate and proportional rate response of the Aveir Atrial Leadless Pacemaker in de novo subjects was tested during staged exercise testing. Exercise test data provided an estimate of the slope of the normalized increase in sensor-indicated rate versus normalized workload for each subject. Normalizing a variable eliminates the unit and expresses it from 0-1.0. Since both axes are normalized sensor rate and workload, there is no distinct unit of measure. Values on the vertical axis are derived from the difference of the sensor indicated rate at each exercise stage and the base rate, divided by the difference of the age-predicted maximum heart rate and base rate. Values on the horizontal axis are derived from the difference in the workload at each exercise stage and resting workload, divided by the difference of the maximum achieved workload and resting workload. A slope value of 1.0 indicates the pacemaker's sensor-indicated rate increases linearly with an increase in workload. |
Countries
Austria, Belgium, Canada, Czechia, France, Hong Kong, Italy, Japan, Netherlands, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORNicole Harbert
Abbott
Participant flow
Recruitment details
Subject enrollment in the Aveir DR i2i IDE study began on February 2, 2022 in Czech Republic, February 24, 2022 in the US, April 7, 2022 in Canada, October 14, 2022 in Hong Kong, and February 9, 2023 in Taiwan. The study enrolled 464 de novo subjects at 77 sites worldwide
Participants by arm
| Arm | Count |
|---|---|
| Enrolled de Novo Cohort With Attempted Implant The enrolled de novo cohort with attempted implant group consisted of subjects that were screened for and met eligibility criteria, provided written informed consent, and had an attempted dual chamber Aveir DR leadless pacemaker system implant | 452 |
| Total | 452 |
Baseline characteristics
| Characteristic | Enrolled de Novo Cohort With Attempted Implant |
|---|---|
| Age, Continuous | 69.8 years STANDARD_DEVIATION 13.3 |
| BMI | 27.8 kg/m^2 STANDARD_DEVIATION 5.7 |
| Height | 170.7 cm STANDARD_DEVIATION 10.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants |
| Race/Ethnicity, Customized Asian | 46 participants |
| Race/Ethnicity, Customized Black or African American | 13 participants |
| Race/Ethnicity, Customized Declined/Unable to Disclose | 104 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 15 Participants |
| Race/Ethnicity, Customized Multi-Racial | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 331 Participants |
| Race/Ethnicity, Customized Unknown | 5 participants |
| Race/Ethnicity, Customized White | 282 participants |
| Region of Enrollment Austria | 5 Participants |
| Region of Enrollment Belgium | 6 Participants |
| Region of Enrollment Canada | 33 Participants |
| Region of Enrollment Czechia | 33 Participants |
| Region of Enrollment France | 18 Participants |
| Region of Enrollment Hong Kong | 11 Participants |
| Region of Enrollment Italy | 7 Participants |
| Region of Enrollment Japan | 24 Participants |
| Region of Enrollment Netherlands | 4 Participants |
| Region of Enrollment Spain | 18 Participants |
| Region of Enrollment Taiwan | 5 Participants |
| Region of Enrollment United Kingdom | 8 Participants |
| Region of Enrollment United States | 280 Participants |
| Sex: Female, Male Female | 174 Participants |
| Sex: Female, Male Male | 278 Participants |
| Weight | 81.6 kg STANDARD_DEVIATION 19.8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 16 / 452 |
| other Total, other adverse events | 366 / 452 |
| serious Total, serious adverse events | 202 / 452 |
Outcome results
Primary
Percentage of Participants Free From Aveir DR System-Related Complications at 12-months
Aveir DR Leadless Pacemaker system complication-free-rate in de novo subjects. A complication was defined as a device-or-procedure-related serious adverse event. Complications included Atrial LP, Ventricular LP, and implant procedure-related complications. Complications possibly related or related to COVID-19 were excluded.
Time frame: 12 months
Population: The primary analysis population for the primary safety endpoint was based on subjects in the full analysis population. The full analysis population included the first 300 consecutive de novo subjects who provided written informed consent and had an attempted implant. A de novo subject was a subject who did not have an implanted pacemaker on the date of consent through the date of the attempted Aveir LP implant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Participants Free From Aveir DR System-Related Complications at 12-months | 88.6 percentage of participants |
p-value: <0.0001one-sided Z-test
Primary
Percentage of Participants Free From Aveir DR System-Related Complications at 3-months
Aveir DR Leadless Pacemaker system complication-free-rate in de novo subjects. A complication was defined as a device-or-procedure-related serious adverse event. Complications included Atrial LP, Ventricular LP, and implant procedure-related complications. Complications possibly related or related to COVID-19 were excluded.
Time frame: 3 months
Population: The primary analysis population for the primary safety endpoint was based on subjects in the full analysis population. The full analysis population included the first 300 consecutive de novo subjects who provided written informed consent and had an attempted implant. A de novo subject was a subject who did not have an implanted pacemaker on the date of consent through the date of the attempted Aveir LP implant
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Participants Free From Aveir DR System-Related Complications at 3-months | 90.3 percentage of participants |
p-value: <0.0001one-sided Z-test
Primary
Percentage of Participants With AV Synchrony Success Rate at Rest While Seated
AV synchrony success was defined as subjects with a paced or sensed ventricular beat within 300 ms following a paced or sensed atrial beat (i.e., a synchronous cycle) for at least 70% of evaluable cardiac cycles.
Time frame: 3 months
Population: Out of 300 subjects in the full analysis population, 2 were excluded due to unsuccessful atrial implants. Then out of 298 subjects, 277 subjects with AV Synchrony data available to define endpoint success were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Participants With AV Synchrony Success Rate at Rest While Seated | 98.2 percentage of participants |
Comparison: The primary effectiveness endpoint #2 hypothesis was formally expressed as:~H0: RateAV ≤ 83% vs. H1: RateAV \> 83%~where 83% is the performance goal.p-value: <0.0001one-sided Z-test
Primary
Percentage of Subjects With Acceptable Atrial Threshold and Amplitude Measurements at 12-months
Composite success rate of acceptable atrial pacing thresholds and P-wave amplitudes in de novo subjects. A subject was considered to have met the success criteria for the endpoint if the pacing threshold voltage was ≤ 3.0 V at 0.4 ms at the 12-month visit and the sensed P-wave amplitude was ≥ 1.0 mV at the 12-month visit.
Time frame: 12 months
Population: Out of 300 subjects, 8 subjects were excluded from primary effectiveness endpoint. 2 were excluded for unsuccessful atrial device implant and 6 were excluded due to unmeasurable P-wave amplitudes and pacing voltages at the 12-month visit due to atrial fibrillation/ atrial tachycardia.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Subjects With Acceptable Atrial Threshold and Amplitude Measurements at 12-months | 92.8 percentage of participants |
Comparison: The primary effectiveness endpoint #1 hypothesis at 12 months was formally expressed as:~H0: Rate ≤ 80% vs. H1: Rate \> 80%~where 80% was the performance goal (PG).p-value: <0.0001one-sided Z-test
Primary
Percentage of Subjects With Acceptable Atrial Threshold and Amplitude Measurements at 3-months
Composite success rate of acceptable atrial pacing thresholds and P-wave amplitudes in de novo subjects. A subject was considered to have met the primary effectiveness endpoint #1 if the pacing threshold voltage was ≤ 3.0 V at 0.4 ms at the 3-month visit and the sensed P-wave amplitude was ≥ 1.0 mV at the 3-month visit.
Time frame: 3 months
Population: Among the 300 subjects in the full analysis population, 3 subjects were excluded due to unsuccessful atrial device implant and unmeasurable p-wave amplitude.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Subjects With Acceptable Atrial Threshold and Amplitude Measurements at 3-months | 90.8 percentage of participants |
Comparison: The primary effectiveness endpoint #1 hypothesis at 3 month was formally expressed as:~H0: Rate ≤ 82.5% vs. H1: Rate \> 82.5%~where 82.5% was the performance goal (PG).p-value: <0.0001one-sided Z-test
Secondary
Percentage of Participants Free From Aveir Atrial Leadless Pacemaker-Related Complications at 12-months
The secondary safety endpoint analysis evaluated the 12-month Atrial LP related complication-free rate (CFRA) based on CEC adjudication of adverse events. An Atrial LP complication was defined as an atrial device-or-procedure-related serious adverse event. Complications that were exclusively related to the Ventricular LP or its delivery/retrieval were not considered Atrial LP complications and were excluded from the evaluation. For a conservative approach, complications that could not exclusively be determined to be related to the ventricular or Atrial LP were still considered Atrial LP complications. For example, procedure-related femoral access complications were adjudicated as Atrial LP complications. Complications possibly related or related to COVID-19 were excluded.
Time frame: 12 months
Population: The analysis population for the secondary safety endpoint was based on subjects in the full analysis population, which included the first 300 consecutive de novo subjects who provided written informed consent and had an attempted implant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Participants Free From Aveir Atrial Leadless Pacemaker-Related Complications at 12-months | 91.0 percentage of participants |
Comparison: The secondary safety endpoint hypothesis at 12 months was formally expressed as:~H0: CFRA ≤ 82% vs. H1: CFRA \> 82%~where 82% is the performance goal.p-value: <0.0001one-sided Z-test
Secondary
Percentage of Participants Free From Aveir Atrial Leadless Pacemaker-Related Complications at 3-months
The secondary safety endpoint evaluated a 3-month Atrial LP related complication-free rate based on CEC adjudication of adverse events. An Atrial LP complication was defined as an atrial device-or-procedure-related serious adverse event. Complications that were exclusively related to the Ventricular LP or its delivery/retrieval were not considered Atrial LP complications and were excluded from the evaluation. For a conservative approach, complications that could not exclusively be determined to be related to the ventricular or Atrial LP were still considered Atrial LP complications. For example, procedure-related femoral access complications were adjudicated as Atrial LP complications.
Time frame: 3 months
Population: The primary analysis population for the secondary safety endpoint was based on subjects in the full analysis population, which included the first 300 consecutive de novo subjects who provided written informed consent and had an attempted implant.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Primary Analysis Population | Percentage of Participants Free From Aveir Atrial Leadless Pacemaker-Related Complications at 3-months | 91.3 percentage of participants |
Comparison: The secondary safety endpoint hypothesis at 3 months was formally expressed as:~H0: CFRA ≤ 84% vs. H1: CFRA \> 84%~where 84% was the performance goal.p-value: 0.0003one-sided Z-test
Secondary
Slope of the Normalized Increase in the Sensor Indicated Rate Versus Normalized Workload of the Aveir Atrial Leadless Pacemaker During Exercise Testing
Appropriate and proportional rate response of the Aveir Atrial Leadless Pacemaker in de novo subjects was tested during staged exercise testing. Exercise test data provided an estimate of the slope of the normalized increase in sensor-indicated rate versus normalized workload for each subject. Normalizing a variable eliminates the unit and expresses it from 0-1.0. Since both axes are normalized sensor rate and workload, there is no distinct unit of measure. Values on the vertical axis are derived from the difference of the sensor indicated rate at each exercise stage and the base rate, divided by the difference of the age-predicted maximum heart rate and base rate. Values on the horizontal axis are derived from the difference in the workload at each exercise stage and resting workload, divided by the difference of the maximum achieved workload and resting workload. A slope value of 1.0 indicates the pacemaker's sensor-indicated rate increases linearly with an increase in workload.
Time frame: 3 months
Population: Subjects with Analyzable CAEP Data
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Primary Analysis Population | Slope of the Normalized Increase in the Sensor Indicated Rate Versus Normalized Workload of the Aveir Atrial Leadless Pacemaker During Exercise Testing | 0.91 unitless |
Comparison: An analysis of these data provided an estimate of the 95% confidence interval for the mean slope across analyzable subjects, which had a pre-specified success criterion requiring that this confidence interval must fall between slopes of 65% and 135%. The following hypothesis was evaluated:~H0: Mean Slope \< 0.65 or Mean Slope \> 1.35~H1: 0.65 ≤ Mean Slope ≤ 1.35p-value: <0.00195% CI: [0.78, 1.04]t-test, 1 sided