Extravascular ICD Pivotal Study (EV ICD)

Extravascular ICD Pivotal Study (EV ICD)

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.

Study Overview

• Status: Completed
• Conditions: Tachycardia; Ventricular Arrythmia
• Intervention / Treatment: Device: Defibrillation using the Extravascular ICD

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.

• Study Type: Interventional
• Enrollment (Actual): 393
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre Clayton
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
• Austria
  • Linz, Austria
    • Kepler Universitätsklinikum Med Campus III.
• Canada
  • London, Canada, N6A 5A5
    • London Health Sciences Centre - University Campus
  • Québec, Canada, G1V 4G5
    • Institut Universitaire de Cardiologie et de Pneumologie de Quebec (IUCPQ)
• Denmark
  • Odense, Denmark, 5000
    • Odense Universitetshospital
• France
  • Chambray-lès-Tours, France, 37170
    • CHRU de Tours - Hôpital Trousseau
  • Rennes, France, 35033
    • CHU de Rennes - Hôpital Pontchaillou
• Hong Kong
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• Hungary
  • Budapest, Hungary
    • Semmelweis Egyetem AOK
• Italy
  • Bologna, Italy, 40138
    • Policlinico Sant' Orsola - Malpighi
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Amsterdam UMC - Locatie AMC
  • Nieuwegein, Netherlands, 3435 CM
    • St. Antonius Ziekenhuis
  • Zwolle, Netherlands, 8025 AB
    • Isala Zwolle
• New Zealand
  • Christchurch, New Zealand
    • Christchurch Hospital
• Norway
  • Oslo, Norway, 0027
    • Oslo Universitetssykehus-Rikshospitalet
• Poland
  • Warszawa, Poland, 04-628
    • Narodowy Instytut Kardiologii - Stefana kardynała Wyszyńskiego
• Saudi Arabia
  • Riyadh, Saudi Arabia, 11472
    • The College of Medicine & King Khalid University Hospital, King Saud University
• Spain
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
• Switzerland
  • Zürich, Switzerland, 8091
    • Universitätsspital Zürich
• United Kingdom
  • London, United Kingdom, WC2R 2LS
    • King's College of London
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Cardiac Arrhythmia Group - Osborn
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego (UCSD)
    • Redwood City, California, United States, 94062
      • Sequoia Hospital
    • Redwood City, California, United States, 94062
      • Continued Access: Sequoia Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Continued Access: Medstar Washington Hospital Center
    • Washington, District of Columbia, United States, 20010
      • MedStar Wahsington Hospital Center
  • Florida
    • Jacksonville, Florida, United States, 32216
      • Baptist Health
    • Jacksonville, Florida, United States, 32216
      • Continued Access: Baptist Health
    • Orlando, Florida, United States, 32803
      • AdventHealth Cardiovascular Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60611-2969
      • Northwestern University
    • Springfield, Illinois, United States, 62769
      • Prairie Education & Research Cooperative
  • Iowa
    • Des Moines, Iowa, United States, 50266
      • Iowa Heart Center
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Cardiovascular Institute of the South
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Minneapolis Heart Institute Foundation
    • Minneapolis, Minnesota, United States, 55455-0363
      • Continued Access: University of Minnesota Medical Center Fairview
    • Minneapolis, Minnesota, United States, 55455-0363
      • University of Minnesota Medical Center Fairview
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Mid America Heart Institute
    • Kansas City, Missouri, United States, 64111
      • Continued Access: Saint Luke's Mid America Heart Institute
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Memorial Hospital
    • Voorhees, New Jersey, United States, 08043
      • Lourdes Cardiology Services
    • Voorhees, New Jersey, United States, 08043
      • Continued Access: Lourdes Cardiology Services
  • New York
    • Manhasset, New York, United States, 11030
      • Continued Access: North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • North Shore Uniersity Hospital
    • New York, New York, United States, 10065-4870
      • New York-Presbyterian Hospital/Weill Cornell Medical Center
    • New York, New York, United States, 10065
      • Continued Access: New York-Presbyterian Hospital/Weill Cornell Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center (DUMC)
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Cleveland, Ohio, United States, 44106
      • Continued Access: University Hospitals Cleveland Clinic Medical Center
    • Columbus, Ohio, United States, 43214
      • OhioHealth Research and Innovation Institute (OHRI)
    • Columbus, Ohio, United States, 43214
      • Continued Access: OhioHealth Research and Innovation Institute (OHRI)
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington (UW) Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Implant Attempt; Patients will be implanted with an extravascular ICD and undergo requisite electrical testing.	Device: Defibrillation using the Extravascular ICD; VT/VF induction attempted for defibrillation testing, as well as requisite electrical testing.
Experimental: Continued Access Implant Attempt; Continued Access for United States	Device: Defibrillation using the Extravascular ICD; VT/VF induction attempted for defibrillation testing, as well as requisite electrical testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	6 Months (182 days) post implant
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.	At Implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continued Access Primary Outcome Measure	The objective of the EV ICD CA study is to allow safe continued access to the EV ICD technology and further develop the product safety and efficacy profile while the product is under review for FDA market approval.	Through study completion, estimated to be 9 months

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Principal Investigator: Paul Friedman, MD, Mayo Clinic

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2019
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): January 4, 2024

Study Registration Dates

• First Submitted: August 14, 2019
• First Submitted That Met QC Criteria: August 16, 2019
• First Posted (Actual): August 19, 2019

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: October 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Tachycardia
• Other Study ID Numbers: U1111-1236-4810; MDT16028 (Other Identifier: Medtronic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes