Multicenter Automatic Defibrillator Implantation Trial With Subcutaneous Implantable Cardioverter Defibrillator

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02787785

Acronym

MADIT S-ICD

Enrollment

Registered

2016-06-01

Start date

2017-04-17

Completion date

2023-06-30

Last updated

2024-08-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiovascular Disease, Diabetes Mellitus, Tachycardia

Keywords

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

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.

Interventions

DEVICESubcutaneous Implantable Cardioverter Defibrillator

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

65 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
All-Cause Mortality	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	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.

Secondary

Measure	Time frame	Description
Sudden Death	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	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.
All-Cause Mortality in Various Subgroups	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	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.

Other

Measure	Time frame	Description
S-ICD Treated Ventricular Arrhythmia Frequency	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	Pre-specific tertiary statistical analyses will be descriptive and exploratory. This describes the number of appropriate shocks received during the study.
S-ICD Treated Ventricular Arrhythmia Outcomes	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	Pre-specific tertiary statistical analyses will be descriptive and exploratory. This describes the number of participants that received an appropriate shock.
S-ICD Device Complications	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	Pre-specific tertiary statistical analyses will be descriptive and exploratory.
S-ICD Inappropriate Shock Frequency	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	Pre-specific tertiary statistical analyses will be descriptive and exploratory. This describes the number of inappropriate shocks received in the study .
S-ICD Inappropriate Shock Outcomes	Outcome measured timeframe includes all available follow-up. Median 61 (4, 71) months.	Pre-specific tertiary statistical analyses will be descriptive and exploratory. This describes the percent of participants that received an inappropriate shock.

Countries

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

Participant flow

Participants by arm

Arm	Count
Conventional Medical Therapy This arm of the trial continued with current conventional medical therapy.	11
Subcutaneous Implantable Cardioverter Defibrillator This arm of the trial received a subcutaneous implantable defibrillator. Subcutaneous Implantable Cardioverter Defibrillator: The S-ICD is an entirely subcutaneous implantable cardioverter defibrillator.	29
Total	40

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	3	4
Overall Study	Lost to Follow-up	1	1
Overall Study	Withdrawal by Subject	0	5

Baseline characteristics

Characteristic	Conventional Medical Therapy	Subcutaneous Implantable Cardioverter Defibrillator	Total
Age, Continuous	70.3 Years STANDARD_DEVIATION 5	71.1 Years STANDARD_DEVIATION 4.7	70.9 Years STANDARD_DEVIATION 4.8
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	5 Participants	7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants	24 Participants	32 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	1 Participants
History of Atrial Fibrillation	2 Participants	8 Participants	10 Participants
History of Ventricular Arrhythmias	1 Participants	6 Participants	7 Participants
Hypertension	11 Participants	24 Participants	35 Participants
New York Heart Association Class (NYHA) NYHA Class I	2 Participants	6 Participants	8 Participants
New York Heart Association Class (NYHA) NYHA Class II	8 Participants	21 Participants	29 Participants
New York Heart Association Class (NYHA) NYHA Class III	1 Participants	2 Participants	3 Participants
Prior CHF Hospitalization	3 Participants	7 Participants	10 Participants
Prior Coronary Artery Bypass Graft	6 Participants	10 Participants	16 Participants
Prior Percutaneous Coronary Intervention	9 Participants	19 Participants	28 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	2 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants	0 Participants	2 Participants
Race (NIH/OMB) White	9 Participants	27 Participants	36 Participants
Region of Enrollment Germany	2 participants	1 participants	3 participants
Region of Enrollment Israel	2 participants	3 participants	5 participants
Region of Enrollment Spain	1 participants	3 participants	4 participants
Region of Enrollment United States	6 participants	22 participants	28 participants
Sex: Female, Male Female	0 Participants	3 Participants	3 Participants
Sex: Female, Male Male	11 Participants	26 Participants	37 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	3 / 11	4 / 29
other Total, other adverse events	4 / 11	17 / 29
serious Total, serious adverse events	8 / 11	20 / 29

Outcome results

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.