Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator

NCT02787785 | Completed Results DMC FDA Device

• 1 other identifier: MADIT S-ICD (C1834)
• Study Type: interventional
• Target: 40
• Locations: 7 countries
• Sites: 49

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.

Conditions

Tachycardia; Diabetes Mellitus; Cardiovascular Disease

Keywords

Subcutaneous; Implantable Cardioverter Defibrillator; MADIT; Diabetes; Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• 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.

  Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.

Secondary Outcomes (2)

• All-Cause Mortality in Various Subgroups

  Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.

• Sudden Death

  Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.

Other Outcomes (5)

• S-ICD Inappropriate Shock Frequency

  Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.

• S-ICD Inappropriate Shock Outcomes

  Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.

• S-ICD Treated Ventricular Arrhythmia Frequency

  Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.

Study Arms (2)

Conventional Medical Therapy

NO INTERVENTION

This arm of the trial continues with their current conventional medical therapy.

Subcutaneous Implantable Cardioverter Defibrillator

ACTIVE COMPARATOR

This arm of the trial receives a subcutaneous implantable defibrillator.

Device: Subcutaneous Implantable Cardioverter Defibrillator

Interventions

Subcutaneous Implantable Cardioverter Defibrillator DEVICE

The S-ICD is an entirely subcutaneous implantable cardioverter defibrillator.

Subcutaneous Implantable Cardioverter Defibrillator

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Boston Scientific Corporation: lead
• University of Rochester: collaborator

Study Sites (49)

Heart Center Research, LLC.

Huntsville, Alabama, 35801, United States

Location

Mayo Clinic- Scottsdale

Scottsdale, Arizona, 85259, United States

Location

St. Bernard's Medical Center

Jonesboro, Arkansas, 72401, United States

Location

Glendale Adventist Medical Center

Glendale, California, 91206, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Cedar-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Alta Bates Summit Hospital

Oakland, California, 94609, United States

Location

Huntington Hospital

Pasadena, California, 91105, United States

Location

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

Location

Emory University

Atlanta, Georgia, 30308, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

St. Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Advanced Cardiovascular Specialists

Shreveport, Louisiana, 71106, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Saint Luke's Hospital

Kansas City, Missouri, 64111, United States

Location

Nebraska Heart Institute

Lincoln, Nebraska, 68526, United States

Location

Catholic Medical Center

Manchester, New Hampshire, 03102, United States

Location

Cardiovascular Associates of Delaware Valley

Haddon Heights, New Jersey, 08035, United States

Location

Northwell Health

Manhasset, New York, 11030, United States

Location

Strong Memorial / University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

North Carolina Heart and Vascular

Raleigh, North Carolina, 27607, United States

Location

Ohio State Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Ohio Health Research Institute

Columbus, Ohio, 43214, United States

Location

Promedica Toledo Hospital

Toledo, Ohio, 43606, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19008, United States

Location

Phoenixville Hospital

Phoenixville, Pennsylvania, 19460, United States

Location

University of Pittsburgh Medical Center - Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

Erlanger Medical Center

Chattanooga, Tennessee, 37403, United States

Location

University of Texas, Houston

Houston, Texas, 77030, United States

Location

Sentara Norfolk General

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

PeaceHealth Southwest Medical Center

Vancouver, Washington, 98664, United States

Location

Medizinische Hochschule Hannover

Hannover, Lower Saxony, 30625, Germany

Location

Unfallkrankenhaus Berlin

Berlin, 12683, Germany

Location

Universitaetsklinik Eppendorf

Hamburg, 20246, Germany

Location

Hadassah Hebrew University Medical Center

Jerusalem, Israel

Location

Kaplan Medical Center

Rehovot, 76100, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Azienda Ospedaliera Ospedale Niguarda CA Granda

Milan, Niguarda, 20162, Italy

Location

Azienda Ospedaliera Universitaria

Verona, 37126, Italy

Location

UMC Utrecht

Utrecht, CX, 3584, Netherlands

Location

Academisch Medisch Centrum

Amsterdam, North Holland, 1105AZ, Netherlands

Location

Hospital Universitario Miguel Servet

Zaragoza, Aragon, 50009, Spain

Location

University of Navarra, Department of Cardiology

Pamplona, Navarre, 31008, Spain

Location

University Hospital Zurich

Zurich, Switzerland

Location

Related 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.

  PMID: 28625372 BACKGROUND

MeSH Terms

Conditions

Tachycardia; Diabetes Mellitus; Cardiovascular Diseases; Myocardial Infarction

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiac Conduction System Disease; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Necrosis

Limitations and Caveats

The primary limitation for MADIT S-ICD was the enrollment stop. The study intended to enroll 1800 subjects; however enrollment was stopped due to slow patient recruitment. The 40 subjects enrolled prior to stopping were followed for a minimum of 5 years for safety. Statistics performed and outcomes included are observational and no longer powered for assessment.

Results Point of Contact

• Title: Clinical Trial Manager or Director of Clinical Trials (Cardiology Rhythm Management)
• Organization: Boston Scientific

jill.leigh@bsci.com

1-800-227-3422

Study Officials

• Valentina Kutyifa, MD, MSc, PhD

  University of Rochester Heart Research Follow-up Program

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2016
• First Posted: June 1, 2016
• Study Start: April 17, 2017
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: August 22, 2024
• Results First Posted: August 22, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (36); IL (3); NL (2); DE (3); IT (2); ES (2); CH (1)