Bradycardia
Conditions
Brief summary
Prospective, non-randomized, single-arm, international multicenter, clinical safety and effectiveness of a leadless pacemaker system in patients who are indicated for a VVIR pacemaker. Following completion of enrollments in the IDE, patients will continue to be enrolled in the continued access phase of the study under the same protocol.
Detailed description
The purpose of this study is to evaluate the safety and effectiveness of the leadless pacemaker system in treating patients with a slow heart rate or irregular heartbeats. The Nanostim leadless pacemaker provides bradycardia pacing as a pulse generator with built-in battery and electrodes, for permanent implantation in the right ventricle. As a leadless pacemaker, it does not need a connector, pacing lead, or pulse generator pocket, but it has the same operating principles as a conventional pacemaker.
Interventions
DEVICELeadless Pacemaker
Patients will undergo an attempted leadless pacemaker implant
Sponsors
Abbott Medical Devices
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must have one of the clinical indications before device implant in adherence with Medicare, ACC/AHA/HRS/ESC single chamber pacing guidelines including: * Chronic and/or permanent atrial fibrillation with 2 or 3° AV or bifascicular bundle branch block (BBB block), including slow ventricular rates (with or without medication) associated with atrial fibrillation; or * Normal sinus rhythm with 2 or 3° AV or BBB block and a low level of physical activity or short expected lifespan (but at least one year); or * Sinus bradycardia with infrequent pauses or unexplained syncope with EP findings; and 2. Subject ≥18 years of age; and 3. Subject has life expectancy of at least one year; and 4. Subject is not enrolled in another clinical investigation; and 5. Subject is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams; and 6. Subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the IRB; and 7. Subject is not pregnant and does not plan to get pregnant during the course of the study.
Exclusion criteria
1. Subject has pacemaker syndrome, has retrograde VA conduction or suffers a drop in arterial blood pressure with the onset of ventricular pacing; or 2. Subject is allergic or hypersensitive to \<1 mg of dexamethasone sodium phosphate; or 3. Subject has a mechanical tricuspid valve prosthesis; or 4. Subject has a pre-existing endocardial pacing or defibrillation leads; or 5. Subject has current implantation of either conventional or subcutaneous implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy (CRT); or 6. Subject has an implanted vena cava filter; or 7. Subject has evidence of thrombosis in one of the veins used for access during the procedure; or 8. Subject has an implanted leadless cardiac pacemaker; or 9. Subject had recent cardiovascular or peripheral vascular surgery within 30 days of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complication-Free Rate | 6 months | Complication is any device-or-procedure related serious adverse event, or serious adverse device effect, including those that prevented initial implantation. Percentage of participants free from complications are reported |
| Pacing Thresholds and R-wave Amplitudes Within the Therapeutic Range | 6 months | Success Rate is percentage of subjects who have acceptable pacing threshold and sensing amplitudes, which are defined as pacing threshold \<=2.0V at 0.4 ms pulse width and R-wave amplitude either =\>5.0 mV at the 6 month visit or =\> value at implant. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Appropriate and Proportional Rate Response During Graded Exercise Testing | 3-6 months | Temperature-based rate response feature was evaluated to determine whether an appropriate and proportional rate response was achieved during maximal effort graded treadmill exercise testing protocol (CAEP). All capable subjects who have completed the 6-minute walk test (6MWT) were asked to perform a maximal effort CAEP exercise protocol to demonstrate an appropriate and proportional response of sensor-indicated rate in graded exercise tests. Data from subjects who have completed the 6MWT and have completed at least stage 3 of the CAEP exercise protocol, or 3.6 metabolic equivalent of task (METs), were included in the analysis. |
Countries
Australia, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Leadless Pacemaker VVIR pacing
Leadless Pacemaker: Patients will undergo an attempted leadless pacemaker implant | 952 |
| Total | 952 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 78 |
| Overall Study | Missed 12-Month Visit | 9 |
| Overall Study | Withdrawn | 57 |
Baseline characteristics
| Characteristic | Leadless Pacemaker |
|---|---|
| Age, Continuous | 75.4 years STANDARD_DEVIATION 12.6 |
| Arrhythmia History Non-Ventricular / Supraventricular | 727 participants |
| Arrhythmia History Ventricular | 43 participants |
| Cardiac Pulmonary History Coronary Artery Disease | 334 participants |
| Cardiac Pulmonary History Myocardial Infarction | 127 participants |
| Cardiac Pulmonary History Prior CABG | 129 participants |
| Cardiac Pulmonary History Prior PTCA / Stents / Atherectomy | 144 participants |
| Cardiac Pulmonary History Unstable Angina | 25 participants |
| Congestive Heart Failure | 149 Participants |
| Diabetes Type I | 14 participants |
| Diabetes Type II | 228 participants |
| Diabetes Current Status Controlled with Diet | 44 participants |
| Diabetes Current Status Controlled with Medication(s) | 191 participants |
| Diabetes Current Status Uncontrolled | 7 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 36 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 913 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Hyperlipidemia Hyperlipidemia Controlled with Diet | 90 participants |
| Hyperlipidemia Hyperlipidemia Controlled with Medication(s) | 509 participants |
| Hyperlipidemia Uncontrolled Hyperlipidemia | 16 participants |
| Hypertension Controlled with Medication(s) | 690 participants |
| Hypertension Controlled Without Medication(s) | 1 participants |
| Hypertension Uncontrolled | 45 participants |
| LV Ejection Fraction | 57.9 percentage STANDARD_DEVIATION 8.1 |
| Medications ACE Inhibitors | 249 participants |
| Medications Angiotensin Receptor Blockers | 167 participants |
| Medications Antiarrhythmics (Class I) | 18 participants |
| Medications Antiarrhythmics (Class III) | 62 participants |
| Medications Anticoagulants | 571 participants |
| Medications Antiplatelets | 407 participants |
| Medications Beta Blockers | 357 participants |
| NYHA Class Class I | 34 participants |
| NYHA Class Class II | 57 participants |
| NYHA Class Class III | 21 participants |
| NYHA Class Not Done | 37 participants |
| Pacemaker Indication Chronic AF with 2nd or 3rd Degree AV Block or Bundle Branch Block, including slow ventricular rates | 529 Participants |
| Pacemaker Indication Sinus Bradycardia with Infrequent Pauses or Unexplained Syncope | 330 Participants |
| Pacemaker Indication Sinus Rhythm with 2nd or 3rd Degree AV Block or Byundle Branch Block | 96 Participants |
| Peripheral Vascular Disease | 113 participants |
| Prior Ablation AFib / Aflutter | 78 participants |
| Prior Ablation AV Nodal | 17 participants |
| Prior Ablation Mini Maze, Thorascope / LAA Ligation | 2 participants |
| Prior Ablation SVT/AVNRT Ablation | 12 participants |
| Prior Ablation Unkown | 1 participants |
| Prior Ablation VT | 2 participants |
| Prior Ablation Wolff-Parkinson-White Syndrome | 2 participants |
| Race/Ethnicity, Customized American Indian / Alaska Native | 3 Participants |
| Race/Ethnicity, Customized Asian | 22 Participants |
| Race/Ethnicity, Customized Black or African American | 61 Participants |
| Race/Ethnicity, Customized Other (Not Specified) | 4 Participants |
| Race/Ethnicity, Customized White or Caucasian | 862 Participants |
| Region of Enrollment Australia | 24 participants |
| Region of Enrollment Canada | 101 participants |
| Region of Enrollment United States | 827 participants |
| Sex: Female, Male Female | 359 Participants |
| Sex: Female, Male Male | 593 Participants |
| Tricuspid Valve Disease Insufficiency / Prolapse / Regurgitation | 184 participants |
| Tricuspid Valve Disease Repair / Replacement | 7 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 276 / 952 |
| other Total, other adverse events | 236 / 952 |
| serious Total, serious adverse events | 436 / 952 |
Outcome results
Primary
Complication-Free Rate
Complication is any device-or-procedure related serious adverse event, or serious adverse device effect, including those that prevented initial implantation. Percentage of participants free from complications are reported
Time frame: 6 months
Population: Analyses of the primary safety and effectiveness endpoints are performed on the Intent to treat (ITT) population. The ITT population is defined as subjects who meet enrollment criteria, provide signed informed consent, and who have an attempted implant of the LP. The study required a sample size of 300 evaluable subjects. The 300-subject primary analysis cohort is defined as the first 300 enrolled subjects sorted by implant date and sheath insertion time.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leadless Pacemaker | Complication-Free Rate | 93.3 percentage of participants |
p-value: <0.00195% CI: [89.9, 95.9]1-sided exact test for binomial proporti
Primary
Pacing Thresholds and R-wave Amplitudes Within the Therapeutic Range
Success Rate is percentage of subjects who have acceptable pacing threshold and sensing amplitudes, which are defined as pacing threshold \<=2.0V at 0.4 ms pulse width and R-wave amplitude either =\>5.0 mV at the 6 month visit or =\> value at implant.
Time frame: 6 months
Population: Analysis of the primary effectiveness endpoints was performed on subjects in the Intent to treat (ITT) population with a successful Nanostim Leadless Pacemaker implanted. This number included 289 of the 300 (96.3%) subjects in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Leadless Pacemaker | Pacing Thresholds and R-wave Amplitudes Within the Therapeutic Range | 93.4 percentage of participants |
p-value: <0.00195% CI: [89.9, 96]1-sided exact test for binomial proporti
Secondary
Appropriate and Proportional Rate Response During Graded Exercise Testing
Temperature-based rate response feature was evaluated to determine whether an appropriate and proportional rate response was achieved during maximal effort graded treadmill exercise testing protocol (CAEP). All capable subjects who have completed the 6-minute walk test (6MWT) were asked to perform a maximal effort CAEP exercise protocol to demonstrate an appropriate and proportional response of sensor-indicated rate in graded exercise tests. Data from subjects who have completed the 6MWT and have completed at least stage 3 of the CAEP exercise protocol, or 3.6 metabolic equivalent of task (METs), were included in the analysis.
Time frame: 3-6 months
Population: Subjects within the enrolled population with a successful implant who completed the six-minute walk test and completed at least stage 3 of the CAEP.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Leadless Pacemaker | Appropriate and Proportional Rate Response During Graded Exercise Testing | 0.83 1/(minutes*metabolic equivalent task) |
p-value: 0.00195% CI: [0.73, 0.93]two 1-sided test (TOST)