Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorCharite University, Berlin, Germany

About this trial

Patients who have survived a myocardial infarction (MI) are at increased risk for sudden cardiac death (SCD) caused by ventricular tachycardia and ventricular fibrillation. A severely reduced left ventricular ejection fraction (LVEF) as a rough overall measure of impaired heart function after MI was shown to indicate a higher risk for SCD. Based on this observation, two landmark randomised trials, MADIT II and SCD-HeFT, were conducted between end of the 1990s and early 2000s. These trials compared the survival of patients with severely reduced LVEF who received an implantable cardioverter-defibrillator with the survival of patients being on medical therapy alone. They reported a significantly better survival of patients in the defibrillator arm and led to international guideline recommendations for routine implantation of defibrillators in survivors of MI with severely impaired LVEF as a means for primary prevention of SCD. Since then, the management of these patients has changed dramatically with the advent of a series of novel drug classes that reduce not only mortality but specifically SCD leading to a substantial decrease of the sudden death rates as well as of the rates of appropriate defibrillator therapies implanted for primary prevention of SCD. At the same time, the complication rates associated with the defibrilllator therapy remain significant without obvious decrease. Thus, the risk-benefit of routine defibrillator implantation for primary prevention of SCD in patients with severely reduced LVEF has substantially changed since the conduction of the landmark trials that established this therapy. Due to the inherent risks and considerable costs of the defibrillator, a novel randomised adequately powered assessment of the potential benefit or harm of the defibrillator in survivors of MI with reduced LVEF under contemporary optimal medical treatment (OMT) appears imperative.

OBJECTIVE:

To demonstrate that in post-MI patients with symptomatic heart failure who receive OMT for this condition, and with reduced LVEF ≤ 35%, OMT without ICD implantation (index group) is not inferior to OMT with ICD implantation (control group) with respect to all-cause mortality.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years.

Naïve to implantation of any pacemaker or defibrillator

Documented history of MI either as ST segment elevation myocardial infarction (STEMI) or as non-ST segment elevation myocardial infarction (NSTEMI) at least 3 months prior to enrolment.

Symptomatic heart failure with New York Heart Association (NYHA) class II or III.

Disqualifiers

Class I or IIa indication for implantation of an ICD for secondary prevention of SCD and ventricular tachycardia.

Ventricular tachycardia induced in an electrophysiologic study.

Unexplained syncope when ventricular arrhythmia is suspected as the cause of syncope.

Class I or IIa indication for Cardiac Resynchronization Therapy (CRT)

Trial design

Design model

Parallel

Treatments tested in this trial

  • Implantable cardioverter-defibrillator (ICD)

    Device

    A transvenous ICD consists of an electronic medical device and electrode leads. Besides the possibility to shock during arrhythmias the ICD can potentially terminate ventricular tachycardias by rapid pacing for short periods (small bursts of pacing). The subcutaneous defibrillator is an established and valid alternative to the transvenous ICD for the prevention of SCD, but in patients without an indication for bradycardia support, cardiac resynchronisation or antitachycardia pacing. The extravascular implantable cardioverter-defibrillator (EV ICD) system with substernal lead placement is a novel nontransvenous alternative to current available transvenous and subcutaneous ICDs.

  • Optimal Medical Therapy (OMT)

    Drug

    Patients will be treated according to Optimal Medical Therapy defined by the following guidelines: 1. 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes 2. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure

Treatment groups

3,595 Participants
are divided into 2 treatment groups
Group A: Optimal Medical Therapy with ICD device therapyActive comparator 2 interventions
Group B: Optimal Medical Therapy without ICD device therapyExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Time from randomisation to the occurrence of all-cause death.

Randomization to end of study

Time frame
event-driven, expected about 15 months after last patient in

Secondary outcomes

1

Time from randomisation to death from cardiovascular causes

Time from randomisation to death from cardiovascular causes

Time frame
Randomization to end of study (event-driven, expected about 15 months after last patient in
2

Time from randomisation to sudden cardiac death

Time from randomisation to sudden cardiac death

Time frame
Randomization to end of study (event-driven, expected about 15 months after last patient in
3

Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation

Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation

Time frame
Randomization to end of study (event-driven, expected about 15 months after last patient in
4

Average length of stay in hospital during the study period

Average length of stay in hospital during the study period

Time frame
Randomization to end of study (event-driven, expected about 15 months after last patient in

Other outcomes

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