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

NCT ID: NCT02433379

Last Updated: 2025-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 1173 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-09
• Study Completion Date: 2019-12-06

Brief Summary

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.

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.

Conditions

Ventricular Fibrillation; Ventricular Tachycardia; Low Cardiac Output

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Single Arm

Subjects implanted with an EMBLEM S-ICD with rate zones set at 200 bpm and 250 bpm per protocol.

Group Type: EXPERIMENTAL

EMBLEM S-ICD System

Intervention Type: DEVICE

The intervention comprises programming the EMBLEM Subcutaneous Implantable Defibrillator (S-ICD) with zone cutoffs at 200 bpm and 250 bmp

Interventions

EMBLEM S-ICD System

The intervention comprises programming the EMBLEM Subcutaneous Implantable Defibrillator (S-ICD) with zone cutoffs at 200 bpm and 250 bmp

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boston Scientific Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Gold, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Lucas Boersma, MD

Role: PRINCIPAL_INVESTIGATOR

St. Antonius Hospital

Locations

Alabama Cardiovascular Group

Birmingham, Alabama, United States

Huntsville Hospital - The Heart Center, PC

Huntsville, Alabama, United States

Mercy Gilbert Medical Center

Gilbert, Arizona, United States

Mayo Clinic Phoenix

Phoenix, Arizona, United States

Glendale Adventist Medical Center

Glendale, California, United States

Sharp Grossmont Hospital

La Mesa, California, United States

University of Southern California Hospital

Los Angeles, California, United States

Alta Bates Medical Center

Oakland, California, United States

St. Joseph Hospital

Orange, California, United States

Good Samaritan Hospital - San Jose

San Jose, California, United States

Harbor UCLA Medical Center

Torrance, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Cardiology Physicians PA

Newark, Delaware, United States

Baptist Medical Center

Jacksonville, Florida, United States

Florida Hospital

Orlando, Florida, United States

Tallahassee Memorial Hospital

Tallahassee, Florida, United States

Emory University Hospital

Atlanta, Georgia, United States

University Hospital

Augusta, Georgia, United States

CorVita Science Foundation

Chicago, Illinois, United States

Northwestern Memorial Hospital

Chicago, Illinois, United States

University of Chicago

Chicago, Illinois, United States

Northern Indiana Research Alliance - Lutheran Hospital

Fort Wayne, Indiana, United States

Methodist Hospital of Indianapolis

Indianapolis, Indiana, United States

St. Vincent's Hospital

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Heartland Cardiology

Wichita, Kansas, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Advanced Cardiovascular Specialists

Shreveport, Louisiana, United States

Peninsula Cardiology Associates

Salisbury, Maryland, United States

St. Joseph Mercy Hospital

Ann Arbor, Michigan, United States

CardioVascular Institute of Michigan P.C.

Roseville, Michigan, United States

William Beaumont Hospital

Royal Oak, Michigan, United States

Centracare Heart and Vascular Center

Saint Cloud, Minnesota, United States

HealthEast St. Joseph's Hospital

Saint Paul, Minnesota, United States

North Mississippi Medical Center

Tupelo, Mississippi, United States

Mercy Research

Springfield, Missouri, United States

Cox Health

Springfield, Missouri, United States

The Nebraska Medical Center

Omaha, Nebraska, United States

HealthCare Partners Cardiology

Las Vegas, Nevada, United States

Deborah Heart and Lung Center

Browns Mills, New Jersey, United States

Cooper Hospital - University Medical Center

Camden, New Jersey, United States

Cardiovascular Associates of the Delaware Valley

Sewell, New Jersey, United States

Albany Medical Center

Albany, New York, United States

Northwell Health

New Hyde Park, New York, United States

Beth Israel Medical Center

New York, New York, United States

Strong Memorial Hospital of the University of Rochester

Rochester, New York, United States

Memorial Mission Hospital

Asheville, North Carolina, United States

University of North Carolina Hospital

Chapel Hill, North Carolina, United States

Durham VA Medical Center

Durham, North Carolina, United States

Rex Hospital

Raleigh, North Carolina, United States

Aultman Hospital

Canton, Ohio, United States

Ohio State University Medical Center

Columbus, Ohio, United States

The Toledo Hospital

Toledo, Ohio, United States

Genesis Healthcare System

Zanesville, Ohio, United States

Salem Hospital

Salem, Oregon, United States

Sacred Heart Medical Center at Riverbend

Springfield, Oregon, United States

Abington Memorial Hospital

Abington, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

AnMed Health

Anderson, South Carolina, United States

Medical University of South Carolina

Charleston, South Carolina, United States

South Texas Veterans Health Care System

San Antonio, Texas, United States

Trinity Mother Frances Health System

Tyler, Texas, United States

University of Utah Hospital and Clinics

Salt Lake City, Utah, United States

Centra Stroobants Cardiovascular Center

Lynchburg, Virginia, United States

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Virginia Commonwealth University Health System

Richmond, Virginia, United States

Evergreen Hospital Medical Center

Kirkland, Washington, United States

CHI Franciscan Health System

Tacoma, Washington, United States

St. Mary's Madison

Madison, Wisconsin, United States

Clinique Saint-Jean

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Institut universitaire de Cardiologie et de Pneumologie de Quebec

Ste-Foy, Quebec, Canada

University Hospital

Odense, , Denmark

CH Annecy

Annecy, , France

CHU Dijon

Dijon, , France

CHRU de Lille

Lille, , France

CHU La Timone Hospital

Marseille, , France

CHU Montpellier

Montpellier, , France

Hospital de la Pitie-Salpetriere

Paris, , France

CHRU Hopital Pontchaillou

Rennes, , France

Nouvel Hôpital Civil De Strasbourg

Strasbourg, , France

Clinique Pasteur

Toulouse, , France

CHRU Nancy Brabois

Vandœuvre-lès-Nancy, , France

Unfallkrankenhaus Berlin Marzahn

Berlin, , Germany

Deutsches Herzzentrum Berlin

Berlin, , Germany

University Hospital Frankfurt

Frankfurt, , Germany

Universitaetsmedizin Greifswald

Greifswald, , Germany

Universitaetsklinik Eppendorf

Hamburg, , Germany

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

University Hospital of Muenster

Münster, , Germany

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, , Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, , Italy

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, , Italy

Academisch Medisch Centrum

Amsterdam, , Netherlands

St. Antonius Ziekenhuis

Nieuwegein, , Netherlands

Erasmus MC - University Medical Center Rotterdam

Rotterdam, , Netherlands

Centralny Szpital Kliniczny Uniwerytetu Medycznego

Lodz, , Poland

Hospital San Lucas

Ponce, , Puerto Rico

Hospital Clinico San Carlos

Madrid, , Spain

Hospital Virgen De La Salud

Toledo, , Spain

Hospital Miguel Servet

Zaragoza, , Spain

Cardiocentro Ticino

Lugano, , Switzerland

University Hospital Zurich

Zurich, , Switzerland

Blackpool Victoria NHS Trust Direct

Blackpool, , United Kingdom

Russels Hall Hospital

Dudley, , United Kingdom

Glenfield Hospital

Leicester, , United Kingdom

Cardiothoracic Centre

Liverpool, , United Kingdom

St. Bartholomews Hospital

London, , United Kingdom

Northern General Hospital

Sheffield, , United Kingdom

Southampton University Hospital

Southampton, , United Kingdom

Countries

United States; Belgium; Canada; Denmark; France; Germany; Italy; Netherlands; Poland; Puerto Rico; Spain; Switzerland; United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 23131066 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 27943348 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31082539 (View on PubMed)

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.

Reference Type: RESULT

PMID: 33073614 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

91026550

Identifier Type: -

Identifier Source: org_study_id