Clinical trial NCT02433379: Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction
Official title: Understanding Outcomes With the EMBLEM™ S-ICD in Primary Prevention Patients With Low Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ventricular Fibrillation
Ventricular Tachycardia
Low Cardiac Output
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
First posted: 2015-05-05
Enrollment: 1173
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Percentage of Patients Who Did Not Experience an Inappropriate Shock From Their EMBLEM S-ICD
timeFrame: 18 months
Secondary outcomes:
measure: Percentage of Participants Not Experiencing a System or Procedure Related Complication From 0 to 30 Days
timeFrame: 30 days
measure: Percentage of Subjects Free From All-cause Shock From Their EMBLEM S-ICD
timeFrame: 18 months
Other outcomes:
measure: Percentage of Patients Not Experiencing a System or Procedure Related Complication From 0 to 180 Days (6 Months).
timeFrame: 6 months
Locations:
city: Birmingham
country: United States
facility: Alabama Cardiovascular Group
state: Alabama
city: Huntsville
country: United States
facility: Huntsville Hospital - The Heart Center, PC
state: Alabama
city: Gilbert
country: United States
facility: Mercy Gilbert Medical Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: La Mesa
country: United States
facility: Sharp Grossmont Hospital
state: California
city: Los Angeles
country: United States
facility: University of Southern California Hospital
state: California
city: Oakland
country: United States
facility: Alta Bates Medical Center
state: California
city: Orange
country: United States
facility: St. Joseph Hospital
state: California
city: San Jose
country: United States
facility: Good Samaritan Hospital - San Jose
state: California
city: Torrance
country: United States
facility: Harbor UCLA Medical Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Newark
country: United States
facility: Cardiology Physicians PA
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Medical Center
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Augusta
country: United States
facility: University Hospital
state: Georgia
city: Chicago
country: United States
facility: CorVita Science Foundation
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Fort Wayne
country: United States
facility: Northern Indiana Research Alliance - Lutheran Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hospital of Indianapolis
state: Indiana
city: Indianapolis
country: United States
facility: St. Vincent's Hospital
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Wichita
country: United States
facility: Heartland Cardiology
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Shreveport
country: United States
facility: Advanced Cardiovascular Specialists
state: Louisiana
city: Salisbury
country: United States
facility: Peninsula Cardiology Associates
state: Maryland
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Roseville
country: United States
facility: CardioVascular Institute of Michigan P.C.
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Saint Cloud
country: United States
facility: Centracare Heart and Vascular Center
state: Minnesota
city: Saint Paul
country: United States
facility: HealthEast St. Joseph's Hospital
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Center
state: Mississippi
city: Springfield
country: United States
facility: Mercy Research
state: Missouri
city: Springfield
country: United States
facility: Cox Health
state: Missouri
city: Omaha
country: United States
facility: The Nebraska Medical Center
state: Nebraska
city: Las Vegas
country: United States
facility: HealthCare Partners Cardiology
state: Nevada
city: Browns Mills
country: United States
facility: Deborah Heart and Lung Center
state: New Jersey
city: Camden
country: United States
facility: Cooper Hospital - University Medical Center
state: New Jersey
city: Sewell
country: United States
facility: Cardiovascular Associates of the Delaware Valley
state: New Jersey
city: Albany
country: United States
facility: Albany Medical Center
state: New York
city: New Hyde Park
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: Rochester
country: United States
facility: Strong Memorial Hospital of the University of Rochester
state: New York
city: Asheville
country: United States
facility: Memorial Mission Hospital
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital
state: North Carolina
city: Durham
country: United States
facility: Durham VA Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Rex Hospital
state: North Carolina
city: Canton
country: United States
facility: Aultman Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Medical Center
state: Ohio
city: Toledo
country: United States
facility: The Toledo Hospital
state: Ohio
city: Zanesville
country: United States
facility: Genesis Healthcare System
state: Ohio
city: Salem
country: United States
facility: Salem Hospital
state: Oregon
city: Springfield
country: United States
facility: Sacred Heart Medical Center at Riverbend
state: Oregon
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Anderson
country: United States
facility: AnMed Health
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: South Texas Veterans Health Care System
state: Texas
city: Tyler
country: United States
facility: Trinity Mother Frances Health System
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Hospital and Clinics
state: Utah
city: Lynchburg
country: United States
facility: Centra Stroobants Cardiovascular Center
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health System
state: Virginia
city: Kirkland
country: United States
facility: Evergreen Hospital Medical Center
state: Washington
city: Tacoma
country: United States
facility: CHI Franciscan Health System
state: Washington
city: Madison
country: United States
facility: St. Mary's Madison
state: Wisconsin
city: Brussels
country: Belgium
facility: Clinique Saint-Jean
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Ste-Foy
country: Canada
facility: Institut universitaire de Cardiologie et de Pneumologie de Quebec
state: Quebec
city: Odense
country: Denmark
facility: University Hospital
city: Annecy
country: France
facility: CH Annecy
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: CHRU de Lille
city: Marseille
country: France
facility: CHU La Timone Hospital
city: Montpellier
country: France
facility: CHU Montpellier
city: Paris
country: France
facility: Hospital de la Pitie-Salpetriere
city: Rennes
country: France
facility: CHRU Hopital Pontchaillou
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil De Strasbourg
city: Toulouse
country: France
facility: Clinique Pasteur
city: Vandoeuvre Les Nancy
country: France
facility: CHRU Nancy Brabois
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin Marzahn
city: Berlin
country: Germany
facility: Deutsches Herzzentrum Berlin
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Greifswald
country: Germany
facility: Universitaetsmedizin Greifswald
city: Hamburg
country: Germany
facility: Universitaetsklinik Eppendorf
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Muenster
country: Germany
facility: University Hospital of Muenster
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC - University Medical Center Rotterdam
city: Lodz
country: Poland
facility: Centralny Szpital Kliniczny Uniwerytetu Medycznego
city: Ponce
country: Puerto Rico
facility: Hospital San Lucas
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Toledo
country: Spain
facility: Hospital Virgen De La Salud
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Lugano
country: Switzerland
facility: Cardiocentro Ticino
city: Zuerich
country: Switzerland
facility: University Hospital Zurich
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria NHS Trust Direct
city: Dudley
country: United Kingdom
facility: Russels Hall Hospital
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
city: Liverpool
country: United Kingdom
facility: Cardiothoracic Centre
city: London
country: United Kingdom
facility: St. Bartholomews Hospital
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
city: Southampton
country: United Kingdom
facility: Southampton University Hospital
Study officials:
affiliation: Medical University of South Carolina
name: Michael Gold, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: St. Antonius Hospital
name: Lucas Boersma, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.