Clinical trial NCT04060680: Extravascular ICD Pivotal Study
Official title: Extravascular ICD Pivotal Study (EV ICD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tachycardia
Ventricular Arrythmia
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2019-08-19
Enrollment: 393
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility 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 exclusion criteria as required by local law (e.g., age or other).
* Pregnant women or breastfeeding women, or women of child bearing potential and who are not on a reliable form of birth regulation method or abstinence.

\[iii\] 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing). \[iv\] ACC/AHA/HRS guidelines for Cardiac Resynchronization Therapy. \[v\] As documented on echo or MRI. \[vi\] As documented on CT scan or MRI.

Continued Access Inclusion Criteria

1. Patient has a Class I or IIa indication for implantation of an ICD according to the ACC/AHA/HRS Guidelines.\[1\]
2. Patient is willing and able to sign and date the Informed Consent Form for their participation in the study.
3. Patient is at least 18 years of age and meets age requirements per local law.
4. Patient is geographically stable and willing and able to comply with the study procedures and visits for the duration of the follow-up.

\[1\] Al-Khatib SM, Stevenson WG, Ackerman MJ, Bryant WJ, Callans DJ, Curtis AB, Deal BJ, Dickfeld T, Field ME, Fonarow GC, Gillis AM, Granger CB, Hammill SC, Hlatky MA, Joglar JA, Kay GN, Matlock DD, Myerburg RJ, Page RL. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2018 Oct 2;72(14):e91-e220. doi: 10.1016/j.jacc.2017.10.054. Epub 2018 Aug 16. Review. Erratum in: J Am Coll Cardiol. 2018 Oct 2;72(14):1760.

Continued Access Exclusion Criteria

1. Patient has indications for bradycardia pacing\[2\] or Cardiac Resynchronization Therapy (CRT)\[3\] (Class I, IIa, or IIb indication).
2. Patients with an existing pacemaker, ICD, or CRT device or leads.
3. 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.
4. 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 that impedes the substernal tunneling path or procedure)
   * 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.
5. Patients with a medical condition that precludes them from undergoing defibrillation testing:

   * Severe aortic stenosis
   * Current 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.
6. Patient with any evidence of active infection or undergoing treatment for an infection.
7. Patient is contraindicated from temporary suspension of oral/systemic anticoagulation.
8. Patient with current implantation of neurostimulator or any other chronically implanted device that delivers current in the body.
9. Patient meets ACC/AHA/HRS or ESC clinical guideline Class III criteria for an ICD (e.g., life expectancy of less than 12 months).
10. 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.
11. Patient with any exclusion criteria as required by local law (e.g., age or other).
12. Pregnant women or breastfeeding women, or women of childbearing potential and who are not on a reliable form of birth regulation method or abstinence\* (\*If required by local law, women of child-bearing potential must undergo a pregnancy test within seven days prior to EV ICD Continued Access Study procedures)

\[2\] Wilkoff BL, Fauchier L, Stiles MK, Morillo CA, Al-Khatib SM, Almendral J, Aguinaga L, Berger RD, Cuesta A, Daubert JP, Dubner S, Ellenbogen KA, Mark Estes NA 3rd, Fenelon G, Garcia FC, Gasparini M, Haines DE, Healey JS, Hurtwitz JL, Keegan R, Kolb C, Kuck KH, Marinskis G, Martinelli M, McGuire M, Molina LG, Okumura K, Proclemer A, Russo AM, Singh JP, Swerdlow CD, Teo WS, Uribe W, Viskin S, Wang CC, Zhang S. 2015 HRS/EHRA/APHRS/SOLAECE expert consensus statement on optimal implantable cardioverter-defibrillator programming and testing. Heart Rhythm. 2016 Feb;13(2):e50-86.

doi: 10.1016/j.hrthm.2015.11.018. Epub 2015 Dec 1. \[3\] Kusumoto FM, Schoenfeld MH, Barrett C, Edgerton JR, Ellenbogen KA, Gold MR, Goldschlager NF, Hamilton RM, Joglar JA, Kim RJ, Lee R, Marine JE, McLeod CJ, Oken KR, Patton KK, Pellegrini CN, Selzman KA, Thompson A, Varosy PD. 2018 ACC/AHA/HRS Guideline on the Evaluation and Management of Patients With Bradycardia and Cardiac Conduction Delay: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019 Aug 20;74(7):e51-e156. doi: 10.1016/j.jacc.2018.10.044. Epub 2018 Nov 6. Erratum in: J Am Coll Cardiol. 2019 Aug 20;74(7):1016-1018.

Primary outcomes:
measure: Safety Outcome - Freedom From Major Complications Related to the EV ICD System and/or Procedure at 6 Months Post-implant
timeFrame: 6 Months (182 days) post implant
measure: Efficacy Outcome - Defibrillation Efficacy at Implant of the EV ICD System
timeFrame: At Implant
Secondary outcomes:
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Cardiac Arrhythmia Group - Osborn
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Redwood City
country: United States
facility: Continued Access: Sequoia Hospital
state: California
city: Redwood City
country: United States
facility: Sequoia Hospital
state: California
city: Washington
country: United States
facility: Continued Access: Medstar Washington Hospital Center
state: District of Columbia
city: Washington
country: United States
facility: MedStar Wahsington Hospital Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Baptist Health
state: Florida
city: Jacksonville
country: United States
facility: Continued Access: Baptist Health
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cardiovascular Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Prairie Education & Research Cooperative
state: Illinois
city: Des Moines
country: United States
facility: Iowa Heart Center
state: Iowa
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Minneapolis
country: United States
facility: Continued Access: University of Minnesota Medical Center Fairview
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center Fairview
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Kansas City
country: United States
facility: Continued Access: Saint Luke's Mid America Heart Institute
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Mid America Heart Institute
state: Missouri
city: Morristown
country: United States
facility: Morristown Memorial Hospital
state: New Jersey
city: Voorhees
country: United States
facility: Continued Access: Lourdes Cardiology Services
state: New Jersey
city: Voorhees
country: United States
facility: Lourdes Cardiology Services
state: New Jersey
city: Manhasset
country: United States
facility: Continued Access: North Shore University Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore Uniersity Hospital
state: New York
city: New York
country: United States
facility: New York-Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: New York
country: United States
facility: Continued Access: New York-Presbyterian Hospital/Weill Cornell Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center (DUMC)
state: North Carolina
city: Cleveland
country: United States
facility: Continued Access: University Hospitals Cleveland Clinic Medical Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Continued Access: OhioHealth Research and Innovation Institute (OHRI)
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research and Innovation Institute (OHRI)
state: Ohio
city: Seattle
country: United States
facility: University of Washington (UW) Medical Center
state: Washington
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Clayton
country: Australia
facility: Monash Medical Centre Clayton
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Linz
country: Austria
facility: Kepler Universitätsklinikum Med Campus III.
city: London
country: Canada
facility: London Health Sciences Centre - University Campus
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ)
city: Odense
country: Denmark
facility: Odense Universitetshospital
city: Chambray-lès-Tours
country: France
facility: CHRU de Tours - Hôpital Trousseau
city: Rennes
country: France
facility: CHU de Rennes - Hôpital Pontchaillou
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK
city: Bologna
country: Italy
facility: Policlinico Sant' Orsola - Malpighi
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC - Locatie AMC
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Zwolle
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Oslo
country: Norway
facility: Oslo Universitetssykehus-Rikshospitalet
city: Warszawa
country: Poland
facility: Narodowy Instytut Kardiologii - Stefana kardynała Wyszyńskiego
city: Riyadh
country: Saudi Arabia
facility: The College of Medicine & King Khalid University Hospital, King Saud University
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Zürich
country: Switzerland
facility: UniversitätsSpital Zürich
city: London
country: United Kingdom
facility: King's College of London
Study officials:
affiliation: Mayo Clinic
name: Paul Friedman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Friedman P, Murgatroyd F, Boersma LVA, Manlucu J, O'Donnell D, Knight BP, Clementy N, Leclercq C, Amin A, Merkely BP, Birgersdotter-Green UM, Chan JYS, Biffi M, Knops RE, Engel G, Munoz Carvajal I, Epstein LM, Sagi V, Johansen JB, Sterlinski M, Steinwender C, Hounshell T, Abben R, Thompson AE, Wiggenhorn C, Willey S, Crozier I; Extravascular ICD Pivotal Study Investigators. Efficacy and Safety of an Extravascular Implantable Cardioverter-Defibrillator. N Engl J Med. 2022 Oct 6;387(14):1292-1302. doi: 10.1056/NEJMoa2206485. Epub 2022 Aug 28.
citation: Crozier I, O'Donnell D, Boersma L, Murgatroyd F, Manlucu J, Knight BP, Birgersdotter-Green UM, Leclercq C, Thompson A, Sawchuk R, Willey S, Wiggenhorn C, Friedman P. The extravascular implantable cardioverter-defibrillator: The pivotal study plan. J Cardiovasc Electrophysiol. 2021 Sep;32(9):2371-2378. doi: 10.1111/jce.15190. Epub 2021 Aug 5.