Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

Not Applicable

Recruiting

• Conditions: Sudden Cardiac Death; Myocardial Infarction
• Interventions: Device: Implantable cardioverter-defibrillator (ICD); Drug: Optimal Medical Therapy (OMT)

• Registration Number: NCT05665608
• Lead Sponsor: Charite University, Berlin, Germany

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-12-19
• Study First Submitted QC: 2022-12-19
• Study First Posted: 2022-12-27
• Study Start: 2023-11-16
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-18
• Primary Completion: 2027-11-30
• Study Completion: 2027-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 3595

Inclusion Criteria

1. Age ≥18 years.
2. Naïve to implantation of any pacemaker or defibrillator
3. 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.
4. Symptomatic heart failure with New York Heart Association (NYHA) class II or III.
5. On OMT for at least 3 months prior to enrolment.
6. LVEF ≤ 35% (at transthoracic echocardiography or cardiac magnetic resonance imaging [MRI] at least 3 months after MI and at least 3 months prior to enrolment.
7. Signed informed consent.

Inclusion criterion I3 defines myocardial infarction according to the 2018 ESC/ACC/AHA/WHF Fourth Universal Definition of myocardial infarction

Exclusion Criteria

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

2. Ventricular tachycardia induced in an electrophysiologic study.

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

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

5. Foreseable violation of instruction for use (IFU) of the ICD device selected for implantation (valid for control group patients, only).

6. Acute coronary syndrome or coronary angioplasty or coronary artery bypass grafting performed within 6 weeks prior to enrolment.

7. Cardiac valve surgery or percutaneous cardiac valvular intervention performed within 6 weeks prior to enrolment.

8. On the waiting list for heart transplantation.

   Class I or IIa indication for implantation of an ICD for secondary prevention of SCD and ventricular tachy-cardia has to be assessed according to the 2022 ESC Guidelines for the management of patients with ven-tricular arrhythmias and the prevention of SCD.

9. Any known disease that limits life expectancy to less than 1 year.

10. Participation in another randomised clinical trial, either within the 3 months prior to enrolment or still on-going.

11. Previous participation in PROFID EHRA.

Parallel participation in sub-studies connected to this trial is permitted as well as in purely observational studies without any pre-defined intervention.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Optimal Medical Therapy with ICD device therapy	Implantable cardioverter-defibrillator (ICD)	Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure / chronic coronary syndromes and will receive an ICD device
Optimal Medical Therapy with ICD device therapy	Optimal Medical Therapy (OMT)	Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure / chronic coronary syndromes and will receive an ICD device
Optimal Medical Therapy without ICD device therapy	Optimal Medical Therapy (OMT)	Patients will be treated according to Optimal Medical Therapy defined by ESC Guidelines for treatment of patients with heart failure / chronic coronary syndromes and will not receive an ICD device

Primary Outcome Measures

Name	Time	Method
Time from randomisation to the occurrence of all-cause death.	event-driven, expected about 15 months after last patient in	Randomization to end of study

Secondary Outcome Measures

Name	Time	Method
Time from randomisation to death from cardiovascular causes	Randomization to end of study (event-driven, expected about 15 months after last patient in	Time from randomisation to death from cardiovascular causes
Time from randomisation to sudden cardiac death	Randomization to end of study (event-driven, expected about 15 months after last patient in	Time from randomisation to sudden cardiac death
Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation	Randomization to end of study (event-driven, expected about 15 months after last patient in	Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation
Average length of stay in hospital during the study period	Randomization to end of study (event-driven, expected about 15 months after last patient in	Average length of stay in hospital during the study period
Quality of life (EQ-5D-5L) trajectories over time	At baseline and 12-month intervals thereafter	Quality of life (EQ-5D-5L) trajectories over time

Trial Locations

Locations (58)

Johannes Wesling Klinikum; 🇩🇪 Minden, Germany

Landeskrankenhaus Feldkirch; 🇦🇹 Feldkirch, Austria

Tirol Kliniken - Universitätsklinik Innsbruck; 🇦🇹 Innsbruck, Austria

Klinikum Klagenfurt am Wörthersee; 🇦🇹 Klagenfurt am Wörthersee, Austria

Ordensklinikum Linz GmbH Elisabethinen; 🇦🇹 Linz, Austria

Landeskrankenhaus Salzburg - Universitätsklinikum der PMU; 🇦🇹 Salzburg, Austria

Universitätsklinikum St. Pölten; 🇦🇹 St. Pölten, Austria

Klinikum Wels-Grieskirchen GmbH; 🇦🇹 Wels, Austria

Universitätsklinikum Wiener Neustadt; 🇦🇹 Wiener Neustadt, Austria

AZ Sint-Jan Brugge-Campus Sint-Jan; 🇧🇪 Brugge, Belgium

Centre hospitaliser régional (CHR) de la Citadelle; 🇧🇪 Liège, Belgium

Centre Hospitalier Universitaire CHU UCL Namur - Site Godinne; 🇧🇪 Yvoir, Belgium

Fakultní Nemocnice Olomouc; 🇨🇿 Olomouc, Czechia

Aarhus University Hospital I; 🇩🇰 Aarhus, Denmark

CHU Amiens Picardie; 🇫🇷 Amiens, France

University Hospital Grenoble-Alpes; 🇫🇷 Grenoble, France

Chu de Rennes; 🇫🇷 Rennes, France

Clinique Pasteur; 🇫🇷 Toulouse, France

St. Marien-Krankenhaus - Klinikum Westmünsterland; 🇩🇪 Ahaus, Germany

Helios Klinikum Aue; 🇩🇪 Aue, Germany

Kerckhoff-Klinik Bad Nauheim; 🇩🇪 Bad Nauheim, Germany

Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum; 🇩🇪 Bad Oeynhausen, Germany

Segeberger Kliniken Gmbh; 🇩🇪 Bad Segeberg, Germany

Charité - Universitätsmedizin Berlin (CCM); 🇩🇪 Berlin, Germany

Sana Klinikum Lichtenberg; 🇩🇪 Berlin, Germany

Charité - Universitätsmedizin Berlin (CBF); 🇩🇪 Berlin, Germany

BG Klinikum Unfallkrankenhaus Berlin; 🇩🇪 Berlin, Germany

Charité - Universitätsmedizin Berlin (CVK); 🇩🇪 Berlin, Germany

Vivantes Humboldt Klinikum; 🇩🇪 Berlin, Germany

Klinikum Bielefeld; 🇩🇪 Bielefeld, Germany

REGIOMED Klinikum Coburg; 🇩🇪 Coburg, Germany

Carl-Thiem-Klinikum; 🇩🇪 Cottbus, Germany

Städtisches Klinikum Dresden; 🇩🇪 Dresden, Germany

Technische Universität Dresden - Herzzentrum Dresden; 🇩🇪 Dresden, Germany

Elisabeth-Krankenhaus Essen; 🇩🇪 Essen, Germany

Universitätsmedizin Greifswald; 🇩🇪 Greifswald, Germany

Georg-August-Universität Göttingen - Universitätsmedizin Göttingen; 🇩🇪 Göttingen, Germany

Klinikum Gütersloh; 🇩🇪 Gütersloh, Germany

Asklepios Kliniken Hamburg; 🇩🇪 Hamburg, Germany

Asklepios Klinikum Harburg; 🇩🇪 Hamburg, Germany

Albertinen Herz- und Gefäßzentrum; 🇩🇪 Hamburg, Germany

Universitätsklinikum Jena; 🇩🇪 Jena, Germany

Westpfalz-Klinikum GmbH; 🇩🇪 Kaiserslautern, Germany

Städtisches Klinikum Karlsruhe; 🇩🇪 Karlsruhe, Germany

Asklepios Kliniken Langen; 🇩🇪 Langen, Germany

Universitätsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Klinikum St. Georg; 🇩🇪 Leipzig, Germany

Herzzentrum Leipzig; 🇩🇪 Leipzig, Germany

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Lübeck, Germany

Klinik Rothenburg ANregiomed; 🇩🇪 Rothenburg ob der Tauber, Germany

Helios Universitätsklinikum Wuppertal; 🇩🇪 Wuppertal, Germany

Semmelweis University; 🇭🇺 Budapest, Hungary

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Universitair Medisch Center Groningen; 🇳🇱 Groningen, Netherlands

Kliniczny Szpital Wojewódzki Nr 2 im.Św.Jadwigi Królowej w Rzeszowie; 🇵🇱 Rzeszów, Poland

Wojskowy Instytut Medyczny; 🇵🇱 Warsaw, Poland

Śląskie Centrum Chorób Serca w Zabrzu; 🇵🇱 Zabrze, Poland

La Paz University Hospital; 🇪🇸 Madrid, Spain