Clinical trial NCT02787785: Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator
Official title: Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator (MADIT S-ICD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tachycardia
Diabetes Mellitus
Cardiovascular Disease
Keywords: Subcutaneous
Implantable Cardioverter Defibrillator
MADIT
Diabetes
Myocardial Infarction
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: University of Rochester
First posted: 2016-06-01
Enrollment: 40
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The MADIT S-ICD trial was designed to evaluate if subjects with a prior myocardial infarction, diabetes mellitus and a relatively preserved ejection fraction of 36-50% will have a survival benefit from receiving a subcutaneous implantable cardioverter defibrillator (S-ICD) when compared to those receiving conventional medical therapy. The trial enrollment was stopped in 2018 due to lower than expected enrollment, all subjects enrolled at that time were followed for approximately 5 years.

Detailed description: In this study, subjects were randomized to receive a subcutaneous implantable cardioverter defibrillator or Conventional Medical Therapy (CMT). Randomization was stratified by enrolling site, in a 2:1 (S-ICD:CMT) scheme. Length of follow-up for each subject was dependent on the date of entry into the study, since all subjects were followed to a common study termination date.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 65 years on date of consent
* Diabetes mellitus treated with oral hypoglycemic agents, non-insulin injectable and/or insulin for the past 3 calendar months or longer prior to consent date
* LV ejection fraction (LVEF) of 36-50% documented by imaging (preferably by MRI or echocardiographic methods), within 12 calendar months before consent date and at least 3 calendar months after most recent Myocardial Infarction (MI), percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG).
* One or more clinically documented, enzyme-positive myocardial infarctions, more than 3 calendar months prior to consent date\*. (If enzyme information and clinical documentation is not available, there must be a clear evidence of prior silent myocardial infarction identified as either new pathologic Q waves on ECG or imaging documentation of an infarcted area (left ventricular angiography/ nuclear scan/ MRI) Note: MI qualification based on the Universal Definition of MI)
* Qualifying 12-lead ECG within 6 calendar months before consent date and at least 3 calendar months after most recent MI, PCI or CABG. (The qualifying ECG\* can be sinus rhythm or atrial fibrillation (patients with persistent or permanent atrial fibrillation should have a controlled ventricular response \<100 bpm on consent date) \*QRS duration on the qualifying ECG \>90 msec)
* Passing S-ICD Screening ECG performed per applicable user's manual on or after the consent date that identifies one or more qualifying S-ICD sensing vectors

Exclusion Criteria:

* Ejection fraction \>50% or \<36% within 12 calendar months prior to consent date and at least 3 calendar months after the most recent MI, PCI or CABG
* Existing guideline based indication for an implantable cardioverter defibrillator (ICD), pacemaker, cardiac resynchronization therapy device (CRT), or cardiac resynchronization therapy device with defibrillator (CRT-D) therapy
* Existing or previously implanted ICD, CRT, CRT-D, or pacemaker device system
* Active infection at the time of consent
* Contraindication for S-ICD implantation according to the S-ICD pulse generator (PG) User's Manual
* Hemodialysis and/or peritoneal dialysis at the time of enrollment
* New York Heart Association Class IV in the past 3 calendar months prior to or at the time of consent date
* Coronary artery bypass graft surgery or percutaneous coronary intervention (balloon and/or stent angioplasty) within 3 calendar months prior to the consent date
* Enzyme-positive myocardial infarction or silent myocardial infarction diagnosed within 3 calendar months prior to the consent date
* Unstable angina with need for outpatient treatment or hospitalization (change/addition of anti-anginal medication and/or coronary revascularization), within 3 calendar months prior to the consent date
* Angiographic evidence of coronary disease in a patient that is a candidate for coronary revascularization and is likely to undergo CABG or PCI in the next 3 calendar months
* High risk for arterial embolism (e.g. presence of mobile left ventricular thrombus)
* Hemodynamically significant congenital heart disease, aortic valvular heart disease, or amyloid heart disease
* Baseline body mass index \> 45 kg/m2
* On a heart transplant list or likely to undergo heart transplant within one calendar year
* Presence of any other disease, other than the subject's cardiac disease, that in the opinion of the investigator is likely to significantly reduce the patient's likelihood of survival for the duration of the trial (e.g. cancer, liver failure).
* Unwillingness or inability to cooperate with the protocol
* Resides at such a distance from the enrolling site so travel to follow-up visits would be unusually difficult
* Reversible causes of heart disease (e.g. viral myocarditis or tachycardia induced cardiomyopathy)
* Participation in other clinical trials (observational registries are allowed with approval from the CDC)
* Does not anticipate residing in the vicinity of the enrolling site for the duration of the trial
* Unwillingness to sign the consent for participation

Primary outcomes:
measure: All-Cause Mortality
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
Secondary outcomes:
measure: All-Cause Mortality in Various Subgroups
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
measure: Sudden Death
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
Other outcomes:
measure: S-ICD Inappropriate Shock Frequency
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
measure: S-ICD Inappropriate Shock Outcomes
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
measure: S-ICD Treated Ventricular Arrhythmia Frequency
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
measure: S-ICD Treated Ventricular Arrhythmia Outcomes
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
measure: S-ICD Device Complications
timeFrame: Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.
Locations:
city: Huntsville
country: United States
facility: Heart Center Research, LLC.
state: Alabama
city: Scottsdale
country: United States
facility: Mayo Clinic- Scottsdale
state: Arizona
city: Jonesboro
country: United States
facility: St. Bernard's Medical Center
state: Arkansas
city: Glendale
country: United States
facility: Glendale Adventist Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: Cedar-Sinai Medical Center
state: California
city: Oakland
country: United States
facility: Alta Bates Summit Hospital
state: California
city: Pasadena
country: United States
facility: Huntington Hospital
state: California
city: Tallahassee
country: United States
facility: Tallahassee Research Institute
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Edgewood
country: United States
facility: St. Elizabeth Healthcare
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Shreveport
country: United States
facility: Advanced Cardiovascular Specialists
state: Louisiana
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Kansas City
country: United States
facility: Saint Luke's Hospital
state: Missouri
city: Lincoln
country: United States
facility: Nebraska Heart Institute
state: Nebraska
city: Manchester
country: United States
facility: Catholic Medical Center
state: New Hampshire
city: Haddon Heights
country: United States
facility: Cardiovascular Associates of Delaware Valley
state: New Jersey
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: Rochester
country: United States
facility: Strong Memorial / University of Rochester Medical Center
state: New York
city: Raleigh
country: United States
facility: North Carolina Heart and Vascular
state: North Carolina
city: Columbus
country: United States
facility: Ohio State Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio Health Research Institute
state: Ohio
city: Toledo
country: United States
facility: Promedica Toledo Hospital
state: Ohio
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Phoenixville
country: United States
facility: Phoenixville Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Presbyterian
state: Pennsylvania
city: Chattanooga
country: United States
facility: Erlanger Medical Center
state: Tennessee
city: Houston
country: United States
facility: University of Texas, Houston
state: Texas
city: Norfolk
country: United States
facility: Sentara Norfolk General
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Vancouver
country: United States
facility: PeaceHealth Southwest Medical Center
state: Washington
city: Hannöver
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Berlin
country: Germany
facility: Unfallkrankenhaus Berlin
city: Hamburg
country: Germany
facility: Universitaetsklinik Eppendorf
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Medical Center
city: Rechovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Milano
country: Italy
facility: Azienda Ospedaliera Ospedale Niguarda CA Granda
state: Niguarda
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria
city: Utrecht
country: Netherlands
facility: UMC Utrecht
state: CX
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
state: NH
city: Zaragosa
country: Spain
facility: Hospital Universitario Miguel Servet
state: Aragon
city: Pamplona
country: Spain
facility: University of Navarra, Department of Cardiology
state: Navarra
city: Zürich
country: Switzerland
facility: University Hospital Zurich
Study officials:
affiliation: University of Rochester Heart Research Follow-up Program
name: Valentina Kutyifa, MD, MSc, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kutyifa V, Beck C, Brown MW, Cannom D, Daubert J, Estes M, Greenberg H, Goldenberg I, Hammes S, Huang D, Klein H, Knops R, Kosiborod M, Poole J, Schuger C, Singh JP, Solomon S, Wilber D, Zareba W, Moss AJ; MADIT S-ICD Executive Committee. Multicenter Automatic Defibrillator Implantation Trial-Subcutaneous Implantable Cardioverter Defibrillator (MADIT S-ICD): Design and clinical protocol. Am Heart J. 2017 Jul;189:158-166. doi: 10.1016/j.ahj.2017.04.014. Epub 2017 May 4.