Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator

Diabetes Mellitus Clinical Trial

— MADIT S-ICD  

Official title:

Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator (MADIT S-ICD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02787785
• Other study ID #: MADIT S-ICD (C1834)
• Status: Completed
• Phase: N/A
• Start date: April 17, 2017
• Est. completion date: June 30, 2023

Study information

• Verified date: May 2024
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Diabetes Mellitus
• Tachycardia

Intervention

Device:
• Subcutaneous Implantable Cardioverter Defibrillator
The S-ICD is an entirely subcutaneous implantable cardioverter defibrillator.

Locations

Country	Name	City	State
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	Universitaetsklinik Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannöver	Niedersachsen
Israel	Hadassah Hebrew University Medical Center	Jerusalem
Israel	Kaplan Medical Center	Rechovot
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Ospedale Niguarda CA Granda	Milano	Niguarda
Italy	Azienda Ospedaliera Universitaria	Verona
Netherlands	Academisch Medisch Centrum	Amsterdam	NH
Netherlands	UMC Utrecht	Utrecht	CX
Spain	University of Navarra, Department of Cardiology	Pamplona	Navarra
Spain	Hospital Universitario Miguel Servet	Zaragosa	Aragon
Switzerland	University Hospital Zurich	Zürich
United States	Abington Memorial Hospital	Abington	Pennsylvania
United States	Emory University	Atlanta	Georgia
United States	Tufts Medical Center	Boston	Massachusetts
United States	Erlanger Medical Center	Chattanooga	Tennessee
United States	Ohio Health Research Institute	Columbus	Ohio
United States	Ohio State Wexner Medical Center	Columbus	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	St. Elizabeth Healthcare	Edgewood	Kentucky
United States	Glendale Adventist Medical Center	Glendale	California
United States	Cardiovascular Associates of Delaware Valley	Haddon Heights	New Jersey
United States	University of Texas, Houston	Houston	Texas
United States	Heart Center Research, LLC.	Huntsville	Alabama
United States	University of Iowa	Iowa City	Iowa
United States	St. Bernard's Medical Center	Jonesboro	Arkansas
United States	Saint Luke's Hospital	Kansas City	Missouri
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	Cedar-Sinai Medical Center	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Catholic Medical Center	Manchester	New Hampshire
United States	Northwell Health	Manhasset	New York
United States	Loyola University Medical Center	Maywood	Illinois
United States	Sentara Norfolk General	Norfolk	Virginia
United States	Alta Bates Summit Hospital	Oakland	California
United States	Huntington Hospital	Pasadena	California
United States	Phoenixville Hospital	Phoenixville	Pennsylvania
United States	University of Pittsburgh Medical Center - Presbyterian	Pittsburgh	Pennsylvania
United States	North Carolina Heart and Vascular	Raleigh	North Carolina
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Strong Memorial / University of Rochester Medical Center	Rochester	New York
United States	Mayo Clinic- Scottsdale	Scottsdale	Arizona
United States	University of Washington	Seattle	Washington
United States	Advanced Cardiovascular Specialists	Shreveport	Louisiana
United States	Tallahassee Research Institute	Tallahassee	Florida
United States	Promedica Toledo Hospital	Toledo	Ohio
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Boston Scientific Corporation	University of Rochester

Countries where clinical trial is conducted

United States,  Germany,  Israel,  Italy,  Netherlands,  Spain,  Switzerland, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	S-ICD Inappropriate shock frequency	Pre-specific tertiary statistical analyses will be descriptive and exploratory	Through study completion,estimated average of 2.6 years follow-up
Other	S-ICD Inappropriate shock outcomes	Pre-specific tertiary statistical analyses will be descriptive and exploratory	Through study completion,estimated average of 2.6 years follow-up
Other	S-ICD treated ventricular arrhythmia frequency	Pre-specific tertiary statistical analyses will be descriptive and exploratory	Through study completion,estimated average of 2.6 years follow-up
Other	S-ICD treated ventricular arrhythmia outcomes	Pre-specific tertiary statistical analyses will be descriptive and exploratory	Through study completion,estimated average of 2.6 years follow-up
Other	S-ICD device complications	Pre-specific tertiary statistical analyses will be descriptive and exploratory	Through study completion, estimated average of 2.6 years follow-up
Primary	All-Cause Mortality	The original study design was event driven with the end date expected to be based on crossing the statistical boundary. 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. The outcomes will be analyzed but are no longer statistically powered for conclusions.	Through study completion,estimated average of 2.6 years follow-up
Secondary	All-Cause Mortality in various subgroups	The original study design was event driven with the end date expected to be based on crossing the statistical boundary. 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. The outcomes will be analyzed but are no longer statistically powered for conclusions.	Through study completion,estimated average of 2.6 years follow-up
Secondary	Sudden Death in various subgroups	The original study design was event driven with the end date expected to be based on crossing the statistical boundary. 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. The outcomes will be analyzed but are no longer statistically powered for conclusions.	Through study completion,estimated average of 2.6 years follow-up