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

Ventricular Tachycardia Clinical Trial

— UNTOUCHED  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02433379
• Other study ID #: 91026550
• Status: Completed
• Phase: N/A
• Start date: June 9, 2015
• Est. completion date: December 6, 2019

Study information

• Verified date: November 2020
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1173
• Est. completion date: December 6, 2019
• Est. primary completion date: December 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Output, Low
• Low Cardiac Output
• Tachycardia
• Tachycardia, Ventricular
• Ventricular Fibrillation
• Ventricular Tachycardia

Intervention

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

Locations

Country	Name	City	State
Belgium	Clinique Saint-Jean	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Institut universitaire de Cardiologie et de Pneumologie de Quebec	Ste-Foy	Quebec
Denmark	University Hospital	Odense
France	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	Vandoeuvre Les Nancy
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	Unfallkrankenhaus Berlin Marzahn	Berlin
Germany	University Hospital Frankfurt	Frankfurt
Germany	Universitaetsmedizin Greifswald	Greifswald
Germany	Universitaetsklinik Eppendorf	Hamburg
Germany	Universitaetsklinikum Heidelberg	Heidelberg
Germany	University Hospital of Muenster	Muenster
Italy	Azienda Ospedaliera Papa Giovanni XXIII	Bergamo
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona
Netherlands	Academisch Medisch Centrum	Amsterdam
Netherlands	St. Antonius Ziekenhuis	Nieuwegein
Netherlands	Erasmus MC - University Medical Center Rotterdam	Rotterdam
Poland	Centralny Szpital Kliniczny Uniwerytetu Medycznego	Lodz
Puerto Rico	Hospital San Lucas	Ponce
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Virgen De La Salud	Toledo
Spain	Hospital Miguel Servet	Zaragoza
Switzerland	Cardiocentro Ticino	Lugano
Switzerland	University Hospital Zurich	Zuerich
United Kingdom	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 States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Albany Medical Center	Albany	New York
United States	AnMed Health	Anderson	South Carolina
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Memorial Mission Hospital	Asheville	North Carolina
United States	Emory University Hospital	Atlanta	Georgia
United States	University Hospital	Augusta	Georgia
United States	Alabama Cardiovascular Group	Birmingham	Alabama
United States	Deborah Heart and Lung Center	Browns Mills	New Jersey
United States	Cooper Hospital - University Medical Center	Camden	New Jersey
United States	Aultman Hospital	Canton	Ohio
United States	University of North Carolina Hospital	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	CorVita Science Foundation	Chicago	Illinois
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Durham VA Medical Center	Durham	North Carolina
United States	Northern Indiana Research Alliance - Lutheran Hospital	Fort Wayne	Indiana
United States	Mercy Gilbert Medical Center	Gilbert	Arizona
United States	Glendale Adventist Medical Center	Glendale	California
United States	Huntsville Hospital - The Heart Center, PC	Huntsville	Alabama
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	Baptist Medical Center	Jacksonville	Florida
United States	Evergreen Hospital Medical Center	Kirkland	Washington
United States	Sharp Grossmont Hospital	La Mesa	California
United States	HealthCare Partners Cardiology	Las Vegas	Nevada
United States	University of Southern California Hospital	Los Angeles	California
United States	Centra Stroobants Cardiovascular Center	Lynchburg	Virginia
United States	St. Mary's Madison	Madison	Wisconsin
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Northwell Health	New Hyde Park	New York
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Beth Israel Medical Center	New York	New York
United States	Cardiology Physicians PA	Newark	Delaware
United States	Sentara Norfolk General Hospital	Norfolk	Virginia
United States	Alta Bates Medical Center	Oakland	California
United States	The Nebraska Medical Center	Omaha	Nebraska
United States	St. Joseph Hospital	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Rex Hospital	Raleigh	North Carolina
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	Strong Memorial Hospital of the University of Rochester	Rochester	New York
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	Salem Hospital	Salem	Oregon
United States	Peninsula Cardiology Associates	Salisbury	Maryland
United States	University of Utah Hospital and Clinics	Salt Lake City	Utah
United States	South Texas Veterans Health Care System	San Antonio	Texas
United States	Good Samaritan Hospital - San Jose	San Jose	California
United States	Cardiovascular Associates of the Delaware Valley	Sewell	New Jersey
United States	Advanced Cardiovascular Specialists	Shreveport	Louisiana
United States	Cox Health	Springfield	Missouri
United States	Mercy Research	Springfield	Missouri
United States	Sacred Heart Medical Center at Riverbend	Springfield	Oregon
United States	CHI Franciscan Health System	Tacoma	Washington
United States	Tallahassee Memorial Hospital	Tallahassee	Florida
United States	The Toledo Hospital	Toledo	Ohio
United States	Harbor UCLA Medical Center	Torrance	California
United States	North Mississippi Medical Center	Tupelo	Mississippi
United States	Trinity Mother Frances Health System	Tyler	Texas
United States	Heartland Cardiology	Wichita	Kansas
United States	Genesis Healthcare System	Zanesville	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Boston Scientific Corporation

Countries where clinical trial is conducted

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

References & Publications (4)

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 Patien — View 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. — View 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 Outco — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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