Tachycardia, Ventricular Arrythmia
Conditions
Brief summary
Pivotal Summary: The study is designed to demonstrate safety and efficacy of the Extravascular Implantable Cardioverter Defibrillator (EV ICD) System. Continued Access Summary: This study is designed to provide continued access to the Extravascular Implantable Cardioverter Defibrillator (EV ICD) System.
Detailed description
The study will enroll subjects who are indicated to receive an implantable defibrillator and who meet all of the inclusion criteria and none of the exclusion criteria. Subjects will receive an investigational Extravascular Implantable Cardioverter Defibrillator (EV ICD) system, in which a lead is placed outside of the heart and veins to deliver defibrillation therapy. Subjects will be followed until regulatory approval is received.
Interventions
VT/VF induction attempted for defibrillation testing, as well as requisite electrical testing.
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Pivotal Inclusion Criteria: * Patient has a Class I or IIa indication for implantation of an ICD according to the ACC/AHA/HRS Guidelines \[i\], or ESC guidelines \[ii\]. * Patient is at least 18 years of age and meets age requirements per local law. * Patient is geographically stable and willing and able to complete the study procedures and visits for the duration of the follow-up. \[i\] Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Hlatky MA, Granger CB, Hammill SC, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias. \[ii\] Priori SG, Blomstrom-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, Elliot PM, Fitzsimons D, Hatala R, Hindricks G, Kirchhof P, Kjeldsen K, Kuck KH, Hernandez-Madrid A, Nikolaou N, Norekval TM, Spaulding C, Van Veldhuisen DJ. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal 2015 36:41 (2793-2867). https://doi.org/10.1093/eurheartj/ehv316 Pivotal
Exclusion criteria
* Patient is unwilling or unable to personally provide Informed Consent. * Patient has indications for bradycardia pacing \[iii\] or Cardiac Resynchronization Therapy (CRT) \[iv\] (Class I, IIa, or IIb indication). * Patient with an existing pacemaker, ICD, or CRT device implant or leads. * Patients with these medical interventions are excluded from participation in the study: * Prior sternotomy * Any prior medical condition or procedure that leads to adhesions in the anterior mediastinal space (i.e., prior mediastinal instrumentation, mediastinitis) * Prior abdominal surgery in the epigastric region * Planned sternotomy * Prior chest radiotherapy Or any other prior/planned medical intervention not listed that precludes their participation in the opinion of the Investigator. * Patient has previous pericarditis that: * Was chronic and recurrent, or * Resulted in pericardial effusion \[v\], or * Resulted in pericardial thickening or calcification \[vi\]. * Patients with these medical conditions or anatomies are excluded from participation in the study: * Hiatal hernia that distorts mediastinal anatomy * Marked sternal abnormality (e.g., pectus excavatum) * Decompensated heart failure * COPD with oxygen dependence * Gross hepatosplenomegaly Or any other known medical condition or anatomy type not listed that precludes their participation in the opinion of the Investigator. * Patients with a medical condition that precludes them from undergoing defibrillation testing: * Severe aortic stenosis * Intracardiac LA or LV thrombus * Severe proximal three-vessel or left main coronary artery disease without revascularization * Hemodynamic instability * Unstable angina * Recent stroke or transient ischemic attack (within the last 6 months) * Known inadequate external defibrillation * LVEF \<20% * LVEDD \>70 mm Or any other known medical condition not listed that precludes their participation in the opinion of the Investigator. * Patient with any evidence of active infection or undergoing treatment for an infection. * Patient is contraindicated from temporary suspension of oral/systemic anticoagulation * Patient with current implantation of neurostimulator or any other chronically implanted device that delivers current in the body. * Patient meets ACC/AHA/HRS or ESC clinical guideline Class III criteria for an ICD (e.g., life expectancy of less than 12 months). * Patient is enrolled or planning to enroll in a concurrent clinical study that may confound the results of this study, without documented pre-approval from a Medtronic study manager. * Patient with any
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcome - Freedom From Major Complications Related to the EV ICD System and/or Procedure at 6 Months Post-implant | 6 Months (182 days) post implant | The primary safety endpoint is defined as a subject's first occurrence of a major complication related to the EV ICD System and/or procedure, as determined by an independent Clinical Events Committee (CEC), that occurs on or prior to 6 months (182 days) post-implant. |
| Efficacy Outcome - Defibrillation Efficacy at Implant of the EV ICD System | At Implant | Each subject will demonstrate a successful defibrillation outcome if either 2 successive induced ventricular fibrillation episodes are terminated by the subject's device delivering a shock at the required energy level, or if one such episode is successfully terminated by the subject's device delivering a shock at a lower energy level. Up to 6 such episodes may be induced to test device efficacy. |
Countries
Australia, Austria, Canada, Denmark, France, Hong Kong, Hungary, Italy, Netherlands, New Zealand, Norway, Poland, Saudi Arabia, Spain, Switzerland, United Kingdom, United States
Participant flow
Recruitment details
The first site was activated on 13SEP2019. The first EV ICD Pivotal subject was enrolled on 16SEP2019 and implanted on the same day. The last subject enrollment occurred on 14OCT2021, and the last implant occurred on 15OCT2021. Sites were notified of enrollment completion on 18OCT2021.
Pre-assignment details
Among 356 enrolled subjects, 40 exited the study without having an implant attempt of the Extravascular ICD System due to: adverse event (2), physician decision (7), procedure not attempted (4), sponsor request (1), withdrawal by subject (10), and other reasons (16).
Participants by arm
| Arm | Count |
|---|---|
| Implant Attempt Pivotal Subjects undergoing an implant attempt of an Extravascular ICD System, including implant testing (sensing, impedance and pacing testing) and induction and defibrillation testing using the Extravascular ICD. | 316 |
| Implant Attempt Continued Access Subjects undergoing an implant attempt of an Extravascular ICD System, including implant testing (sensing, impedance and pacing testing) and induction and defibrillation testing using the Extravascular ICD. | 33 |
| Total | 349 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Death | 2 | 0 |
| Overall Study | Study product no longer in use | 1 | 0 |
| Overall Study | Unsuccessful implant | 17 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Implant Attempt Pivotal | Implant Attempt Continued Access | Total |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 13.1 | 49.2 years STANDARD_DEVIATION 13.9 | 53.4 years STANDARD_DEVIATION 13.2 |
| Body Mass Index | 28.0 kg/m^2 STANDARD_DEVIATION 5.6 | 31 kg/m^2 STANDARD_DEVIATION 8 | 28.3 kg/m^2 STANDARD_DEVIATION 5.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 110 Participants | 29 Participants | 139 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 199 Participants | 2 Participants | 201 Participants |
| ICD Indication Other | 1 Participants | 1 Participants | 2 Participants |
| ICD Indication Primary Prevention | 258 Participants | 17 Participants | 275 Participants |
| ICD Indication Secondary Prevention | 57 Participants | 15 Participants | 72 Participants |
| New York Heart Association Classification Not Available | 34 Participants | 1 Participants | 35 Participants |
| New York Heart Association Class III: Marked limitation of physical activity. | 23 Participants | 3 Participants | 26 Participants |
| New York Heart Association Class II: Slight limitation of physical activity. | 184 Participants | 15 Participants | 199 Participants |
| New York Heart Association Class I: No symptoms and no limitations in ordinary physical activity. | 75 Participants | 4 Participants | 79 Participants |
| New York Heart Association Class IV: Unable to carry on any physical activity without discomfort. Symptoms at rest. | 0 Participants | 0 Participants | 0 Participants |
| New York Heart Association No Heart Failure | 0 Participants | 10 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 7 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 197 Participants | 2 Participants | 199 Participants |
| Race (NIH/OMB) White | 87 Participants | 21 Participants | 108 Participants |
| Region Asia Pacific | 37 Participants | 0 Participants | 37 Participants |
| Region Europe, Middle East, and Africa | 159 Participants | 0 Participants | 159 Participants |
| Region North America | 120 Participants | 33 Participants | 153 Participants |
| Sex: Female, Male Female | 80 Participants | 9 Participants | 89 Participants |
| Sex: Female, Male Male | 236 Participants | 24 Participants | 260 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 356 | 1 / 37 |
| other Total, other adverse events | 20 / 356 | 2 / 37 |
| serious Total, serious adverse events | 172 / 356 | 6 / 37 |
Outcome results
Primary
Efficacy Outcome - Defibrillation Efficacy at Implant of the EV ICD System
Each subject will demonstrate a successful defibrillation outcome if either 2 successive induced ventricular fibrillation episodes are terminated by the subject's device delivering a shock at the required energy level, or if one such episode is successfully terminated by the subject's device delivering a shock at a lower energy level. Up to 6 such episodes may be induced to test device efficacy.
Time frame: At Implant
Population: Subjects who completed the implant defibrillation testing protocol
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implant Attempt | Efficacy Outcome - Defibrillation Efficacy at Implant of the EV ICD System | 298 Participants |
Comparison: The primary efficacy is to demonstrate the EV ICD defibrillation testing success rate at implant is greater than an OPC of 88%. H0: p ≤ 0.88 HA: p \> 0.88, where p denotes the probability of EV ICD defibrillation success at implant.p-value: <0.000195% CI: [96.6, 99.6]One-proportion binomial exact test
Primary
Safety Outcome - Freedom From Major Complications Related to the EV ICD System and/or Procedure at 6 Months Post-implant
The primary safety endpoint is defined as a subject's first occurrence of a major complication related to the EV ICD System and/or procedure, as determined by an independent Clinical Events Committee (CEC), that occurs on or prior to 6 months (182 days) post-implant.
Time frame: 6 Months (182 days) post implant
Population: Subjects who underwent an implant attempt of the Extravascular ICD System
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Implant Attempt | Safety Outcome - Freedom From Major Complications Related to the EV ICD System and/or Procedure at 6 Months Post-implant | 293 Participants |
Comparison: The primary safety objective is to demonstrate the freedom from major complications related to the EV ICD System and/or procedure at 6 months post-implant exceeds an OPC of 79%. H0: p ≤ 0.79 HA: p \> 0.79, where p denotes the 6-month (182 days) freedom from major EV ICD System/procedure-related complications rate.p-value: <0.000195% CI: [89, 95]Kaplan-Meier method