Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED)

This study assesses the 18-month incidence of inappropriate shocks in subjects implanted with the EMBLEM Subcutaneous Implantable Defibrillator (S-ICD) for primary prevention of sudden cardiac death. Devices are to be programmed with zone cutoffs at 200 bpm and 250 bmp in order to mimic the programming settings for transvenous ICDs in the MADIT RIT study. The incidence of inappropriate S-ICD shocks will be compared to the incidence of inappropriate shocks observed in the MADIT RIT study.

Study Overview

• Status: Completed
• Conditions: Ventricular Fibrillation; Ventricular Tachycardia; Low Cardiac Output
• Intervention / Treatment: Device: EMBLEM S-ICD System

Detailed Description

Implantable cardioverter defibrillator (ICD) therapy is highly effective for reducing mortality in patients with clinical markers for elevated risk for ventricular arrhythmias. However, inappropriate shocks and unnecessary appropriate shocks remain an important side effect that can significantly affect an ICD recipient's quality of life and may be deleterious to the myocardium.

The MADIT RIT study demonstrated that the incidence of inappropriate and unnecessary appropriate ICD therapy can be reduced in primary prevention patients through two different programming strategies: 1) High Rate Zone Cutoff, i.e., raising the lowest rate detection cutoff to 200 bpm; and 2) Delayed Therapy Initiation, i.e., increasing the time to therapy initiation to 60 seconds for arrhythmias detected between 170-199 bpm and 12.5 seconds between 200-249 bpm. Both strategies effectively reduced the amount of ICD therapy delivered when compared to conventional programming, where the lowest rate detection cutoff was 170 bpm and the delay to therapy initiation was programmed to 2.5 seconds. Importantly, neither treatment arm was associated with significantly increased syncope or mortality. The results of MADIT RIT established preferred device settings for reducing shocks in transvenous ICD (TV-ICD) patients with a primary prevention indication.

Preferred settings for subcutaneous ICDs, however, have not been established with data from prospective studies. The UNTOUCHED study will test a programming scheme designed to minimize inappropriate and unnecessary shocks in patients who have an indication for primary prevention of sudden cardiac death and low ejection fraction. Although S-ICD programming options do not permit exact replication of the programmed settings previously shown to reduce shocks in the MADIT RIT treatment arms, key elements are combined into the UNTOUCHED settings to be tested in this protocol. It is hypothesized that despite the lack of anti-tachycardia pacing, the EMBLEM S-ICD settings utilized in this study will result in an overall shock incidence similar to that observed in ICD patients from MADIT RIT.

• Study Type: Interventional
• Enrollment (Actual): 1173
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1000
    • Clinique Saint-Jean
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• Canada
  • Quebec
    • Ste-Foy, Quebec, Canada, G1V 4G5
      • Institut Universitaire de Cardiologie et de Pneumologie de Quebec
• Denmark
  • Odense, Denmark, 5000
    • University Hospital
• France
  • Annecy, France, 74011
    • CH Annecy
  • Dijon, France, 21079
    • CHU Dijon
  • Lille, France
    • CHRU de Lille
  • Marseille, France, 13005
    • CHU La Timone Hospital
  • Montpellier, France, 34295
    • CHU Montpellier
  • Paris, France, 75151
    • Hospital de la Pitie-Salpetriere
  • Rennes, France
    • CHRU Hopital Pontchaillou
  • Strasbourg, France, 67091
    • Nouvel Hôpital Civil de Strasbourg
  • Toulouse, France, 31076
    • Clinique Pasteur
  • Vandoeuvre Les Nancy, France, 54500
    • Chru Nancy Brabois
• Germany
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin
  • Berlin, Germany, 12687
    • Unfallkrankenhaus Berlin Marzahn
  • Frankfurt, Germany, 60590
    • University Hospital Frankfurt
  • Greifswald, Germany, 17475
    • Universitaetsmedizin Greifswald
  • Hamburg, Germany, 20246
    • Universitaetsklinik Eppendorf
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Muenster, Germany, 48149
    • University Hospital of Muenster
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni XXIII
  • Pisa, Italy, 56127
    • Azienda Ospedaliero Universitaria Pisana
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata di Verona
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum
  • Nieuwegein, Netherlands, 3430 EM
    • St. Antonius Ziekenhuis
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus MC - University Medical Center Rotterdam
• Poland
  • Lodz, Poland, 92-213
    • Centralny Szpital Kliniczny Uniwerytetu Medycznego
• Puerto Rico
  • Ponce, Puerto Rico, 00733
    • Hospital San Lucas
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Toledo, Spain, 45004
    • Hospital Virgen de la Salud
  • Zaragoza, Spain
    • Hospital Miguel Servet
• Switzerland
  • Lugano, Switzerland, 6900
    • Cardiocentro Ticino
  • Zuerich, Switzerland, 8091
    • University Hospital Zurich
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Blackpool Victoria NHS Trust Direct
  • Dudley, United Kingdom
    • Russels Hall Hospital
  • Leicester, United Kingdom
    • Glenfield Hospital
  • Liverpool, United Kingdom, L14 3PE
    • Cardiothoracic Centre
  • London, United Kingdom, EC1A 7BE
    • St. Bartholomews Hospital
  • Sheffield, United Kingdom, S5 7AU
    • Northern General Hospital
  • Southampton, United Kingdom, S016 6YD
    • Southampton University Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Alabama cardiovascular group
    • Huntsville, Alabama, United States, 35801
      • Huntsville Hospital - The Heart Center, PC
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Mercy Gilbert Medical Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • California
    • Glendale, California, United States, 91206
      • Glendale Adventist Medical Center
    • La Mesa, California, United States, 91942
      • Sharp Grossmont Hospital
    • Los Angeles, California, United States, 90033-4612
      • University of Southern California Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Medical Center
    • Orange, California, United States, 92868
      • St. Joseph Hospital
    • San Jose, California, United States, 95124
      • Good Samaritan Hospital - San Jose
    • Torrance, California, United States, 90502
      • Harbor Ucla Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine
  • Delaware
    • Newark, Delaware, United States, 19713
      • Cardiology Physicians PA
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Medical Center
    • Orlando, Florida, United States, 32803
      • Florida Hospital
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Augusta, Georgia, United States, 30901
      • University Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
    • Chicago, Illinois, United States, 60605
      • CorVita Science Foundation
  • Indiana
    • Fort Wayne, Indiana, United States, 60611
      • Northern Indiana Research Alliance - Lutheran Hospital
    • Indianapolis, Indiana, United States, 46260
      • St. Vincent's Hospital
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hospital of Indianapolis
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Heartland Cardiology
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
    • Shreveport, Louisiana, United States, 71103
      • Advanced Cardiovascular Specialists
  • Maryland
    • Salisbury, Maryland, United States, 21804
      • Peninsula Cardiology Associates
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • St. Joseph Mercy Hospital
    • Roseville, Michigan, United States, 48066
      • CardioVascular Institute of Michigan P.C.
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Minnesota
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Heart and Vascular Center
    • Saint Paul, Minnesota, United States, 55102
      • HealthEast St. Joseph's Hospital
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Center
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Mercy Research
    • Springfield, Missouri, United States, 65807
      • Cox Health
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • The Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • HealthCare Partners Cardiology
  • New Jersey
    • Browns Mills, New Jersey, United States, 08015
      • Deborah Heart and Lung Center
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital - University Medical Center
    • Sewell, New Jersey, United States, 08080
      • Cardiovascular Associates of the Delaware Valley
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • New Hyde Park, New York, United States, 11040
      • Northwell Health
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • Rochester, New York, United States, 14642
      • Strong Memorial Hospital of the University of Rochester
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Memorial Mission Hospital
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Hospital
    • Durham, North Carolina, United States, 27705
      • Durham VA Medical Center
    • Raleigh, North Carolina, United States, 27607
      • Rex Hospital
  • Ohio
    • Canton, Ohio, United States, 44710
      • Aultman Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
    • Toledo, Ohio, United States, 43606
      • The Toledo Hospital
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System
  • Oregon
    • Salem, Oregon, United States, 97301
      • Salem Hospital
    • Springfield, Oregon, United States, 97477
      • Sacred Heart Medical Center at Riverbend
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health
    • Charleston, South Carolina, United States, 29425-0001
      • Medical University of South Carolina
  • Texas
    • San Antonio, Texas, United States, 78229
      • South Texas Veterans Health Care System
    • Tyler, Texas, United States, 75701
      • Trinity Mother Frances Health System
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Hospital and Clinics
  • Virginia
    • Lynchburg, Virginia, United States, 24501
      • Centra Stroobants Cardiovascular Center
    • Norfolk, Virginia, United States, 23507
      • Sentara Norfolk General Hospital
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Health System
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Hospital Medical Center
    • Tacoma, Washington, United States, 98405
      • CHI Franciscan Health System
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • St. Mary's Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient with ischemic or non-ischemic heart disease who meets current guidelines for ICD therapy and intends to undergo a de novo implant procedure for an EMBLEM™ S-ICD (or newer generation BSC S-ICD)
• Left ventricular ejection fraction ≤ 35%
• A passing EMBLEM™ S-ICD (or newer generation BSC S-ICD) screening ECG
• Patient ≥ 21 years of age willing and capable of giving informed consent
• Patient willing and capable of complying with follow-up visits

Exclusion Criteria:

• Patient with a history of spontaneous sustained VT or VF
• Patient with bradycardia pacing indication
• Patient eligible and scheduled for cardiac resynchronization implant
• Patient with a previous S-ICD or a previous transvenous pulse generator (pacemaker or defibrillator)
• Patient in NYHA Class IV documented in the medical records within 90 days before enrollment
• Patient with life expectancy shorter than 18 months due to any medical condition (e.g., cancer, uremia, liver failure, etc…)
• Patient receiving hemodialysis within 180 days before to enrollment
• Patients unable to give consent in person, including patients unable to read or write
• Patient who is known to be pregnant or plans to become pregnant over the course of the trial
• Patient unwilling or unable to cooperate with the protocol
• Participation in concurrent clinical study without prior approval from Boston Scientific
• Medical status (e.g., hemodynamic conditions ) of the patient doesn't allow programming devices with a conditional shock zone at 200 bpm and a shock zone at 250 bpm, in the judgment of the implanting physician and/or according to (inter) national guidelines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm; Subjects implanted with an EMBLEM S-ICD with rate zones set at 200 bpm and 250 bpm per protocol.	Device: EMBLEM S-ICD System; The intervention comprises programming the EMBLEM Subcutaneous Implantable Defibrillator (S-ICD) with zone cutoffs at 200 bpm and 250 bmp

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Did Not Experience an Inappropriate Shock From Their EMBLEM S-ICD	Primary endpoint: Inappropriate shock free rate from 0 to 540 Days (18-Months) compared to a performance goal of 91.6%.	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Not Experiencing a System or Procedure Related Complication From 0 to 30 Days	Secondary safety endpoint: Freedom from System and Procedure Related Complications at 30 days compared to a performance goal of 93.8%.	30 days
Percentage of Subjects Free From All-cause Shock From Their EMBLEM S-ICD	Secondary efficacy endpoint: All-Cause Shock Free Rate at 540 days (18-months) compared to a performance goal of 85.8%.	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Not Experiencing a System or Procedure Related Complication From 0 to 180 Days (6 Months).	Post-Market Clinical Follow-up (PMCF) Endpoint: Freedom from System and Procedure Related Complications at 180 days (6 months) compared to a performance goal of 85%. This analysis was conducted for two sub-groups of UNTOUCHED Study subjects: 1.) the first 200 subjects implanted with an EMBLEM model A209 device; 2.) the first 200 subjects implanted with an EMBLEM model A219 device. The PMCF analysis prespecified in the study protocol only required a sub-set of the implanted UNTOUCHED Study subjects (i.e., 200 subjects for the EMBLEM A209 analysis and 200 for the EMBLEM A219 analysis; the full study cohort was not required for these two analyses).	6 months

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Investigators: Principal Investigator: Michael Gold, MD, Medical University of South Carolina; Principal Investigator: Lucas Boersma, MD, St. Antonius Ziekenhuis

Publications and helpful links

General Publications

• Moss AJ, Schuger C, Beck CA, Brown MW, Cannom DS, Daubert JP, Estes NA 3rd, Greenberg H, Hall WJ, Huang DT, Kautzner J, Klein H, McNitt S, Olshansky B, Shoda M, Wilber D, Zareba W; MADIT-RIT Trial Investigators. Reduction in inappropriate therapy and mortality through ICD programming. N Engl J Med. 2012 Dec 13;367(24):2275-83. doi: 10.1056/NEJMoa1211107. Epub 2012 Nov 6.
• Gold MR, Knops R, Burke MC, Lambiase PD, Russo AM, Bongiorni MG, Deharo JC, Aasbo J, El Chami MF, Husby M, Carter N, Boersma L. The Design of the Understanding Outcomes with the S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED). Pacing Clin Electrophysiol. 2017 Jan;40(1):1-8. doi: 10.1111/pace.12994. Epub 2017 Jan 15.
• Boersma LV, El-Chami MF, Bongiorni MG, Burke MC, Knops RE, Aasbo JD, Lambiase PD, Deharo JC, Russo AM, Dinerman J, Shaik N, Barr CS, Carter N, Appl U, Brisben AJ, Stein KM, Gold MR. Understanding Outcomes with the EMBLEM S-ICD in Primary Prevention Patients with Low EF Study (UNTOUCHED): Clinical characteristics and perioperative results. Heart Rhythm. 2019 Nov;16(11):1636-1644. doi: 10.1016/j.hrthm.2019.04.048. Epub 2019 May 10.
• Gold MR, Lambiase PD, El-Chami MF, Knops RE, Aasbo JD, Bongiorni MG, Russo AM, Deharo JC, Burke MC, Dinerman J, Barr CS, Shaik N, Carter N, Stoltz T, Stein KM, Brisben AJ, Boersma LVA; UNTOUCHED Investigators*. Primary Results From the Understanding Outcomes With the S-ICD in Primary Prevention Patients With Low Ejection Fraction (UNTOUCHED) Trial. Circulation. 2021 Jan 5;143(1):7-17. doi: 10.1161/CIRCULATIONAHA.120.048728. Epub 2020 Oct 19.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2015
• Primary Completion (Actual): December 6, 2019
• Study Completion (Actual): December 6, 2019

Study Registration Dates

• First Submitted: April 23, 2015
• First Submitted That Met QC Criteria: April 29, 2015
• First Posted (Estimate): May 5, 2015

Study Record Updates

• Last Update Posted (Actual): August 17, 2021
• Last Update Submitted That Met QC Criteria: August 16, 2021
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Ventricular Fibrillation; Tachycardia; Tachycardia, Ventricular; Cardiac Output, Low
• Other Study ID Numbers: 91026550

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