Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation (PROFID EHRA)

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.

Study Overview

• Status: Recruiting
• Conditions: Myocardial Infarction; Sudden Cardiac Death
• Intervention / Treatment: Device: Implantable cardioverter-defibrillator (ICD); Drug: Optimal Medical Therapy (OMT)

• Study Type: Interventional
• Enrollment (Estimated): 3595
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gerhard Hindricks, Prof; Phone Number: +49 30 450 513211; Email: Gerhard.Hindricks@dhzc-charite.de
• Study Contact Backup: Name: Nikolaos Dagres, MD; Phone Number: +49 30 450 665407; Email: Nikolaos.Dagres@dhzc-charite.de

Study Locations

• Austria
  • Feldkirch, Austria, 6800
    • Recruiting
    • Landeskrankenhaus Feldkirch
  • Graz, Austria, 8036
    • Recruiting
    • LKH Universitätsklinikum Graz
  • Innsbruck, Austria, 6020
    • Recruiting
    • Tirol Kliniken - Universitätsklinik Innsbruck
  • Klagenfurt, Austria, 9020
    • Recruiting
    • Klinikum Klagenfurt am Wörthersee
  • Linz, Austria, 4020
    • Recruiting
    • Ordensklinikum Linz GmbH Elisabethinen
  • Salzburg, Austria, 5020
    • Recruiting
    • Landeskrankenhaus Salzburg - Universitätsklinikum der PMU
  • Sankt Pölten, Austria, 3100
    • Recruiting
    • Universitätsklinikum St. Pölten
  • Wels, Austria, 4600
    • Recruiting
    • Klinikum Wels-Grieskirchen GmbH
  • Wiener Neustadt, Austria, 2700
    • Recruiting
    • Universitätsklinikum Wiener Neustadt
• Belgium
  • Aalst, Belgium, 9300
    • Recruiting
    • OLV Ziekenhuis Campus Aalst
  • Bruges, Belgium, 8000
    • Recruiting
    • AZ Sint-Jan Brugge-Campus Sint-Jan
  • Liège, Belgium, 4000
    • Recruiting
    • Centre hospitaliser régional (CHR) de la Citadelle
  • Yvoir, Belgium, 5530
    • Recruiting
    • Centre Hospitalier Universitaire CHU UCL Namur - Site Godinne
• Czechia
  • Olomouc, Czechia, 779 00
    • Terminated
    • Fakultni nemocnice Olomouc
  • Prague, Czechia, 128 08
    • Recruiting
    • Všeobecná fakultní nemocnice v Praze
  • Prague, Czechia, 140 21
    • Recruiting
    • Institut klinicke a experimentalni mediciny
  • Ústí nad Labem, Czechia, 400 11
    • Recruiting
    • Masaryk Hospital
• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital I
• France
  • Amiens, France, 80054
    • Recruiting
    • CHU Amiens Picardie
  • Brest, France, 29609
    • Recruiting
    • Hôpital de la Cavale Blanche-CHU BREST
  • Créteil, France, 94010
    • Recruiting
    • Chu Henri Mondor
  • Grenoble, France, 38700
    • Recruiting
    • University Hospital Grenoble-Alpes
  • Paris, France, 75018
    • Recruiting
    • Hopital Bichat Claude Bernard
  • Paris, France, 75015
    • Recruiting
    • Européen Georges Pompidou Hospital Paris
  • Rennes, France, 35000
    • Recruiting
    • CHU de Rennes
  • Saint-Denis, France, 93200
    • Recruiting
    • Centre Cardiologique du Nord
  • Toulouse, France, 31076
    • Recruiting
    • Clinique Pasteur
  • Toulouse, France, 31059
    • Recruiting
    • University Hospital Rangueil Toulouse
• Germany
  • Ahaus, Germany, 48683
    • Withdrawn
    • St. Marien-Krankenhaus - Klinikum Westmünsterland
  • Aue, Germany, 08280
    • Recruiting
    • Helios Klinikum Aue
  • Bad Nauheim, Germany, 61231
    • Recruiting
    • Kerckhoff-Klinik Bad Nauheim
  • Bad Oeynhausen, Germany, 32545
    • Recruiting
    • Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum
  • Bad Segeberg, Germany, 23795
    • Recruiting
    • Segeberger Kliniken GmbH
  • Berlin, Germany, 12203
    • Recruiting
    • Charité - Universitätsmedizin Berlin (CBF)
  • Berlin, Germany, 10365
    • Recruiting
    • Sana Klinikum Lichtenberg
  • Berlin, Germany, 13353
    • Recruiting
    • Charité - Universitätsmedizin Berlin (CVK)
  • Berlin, Germany, 12683
    • Recruiting
    • BG Klinikum Unfallkrankenhaus Berlin
  • Berlin, Germany, 10117
    • Recruiting
    • Charité - Universitätsmedizin Berlin (CCM)
  • Berlin, Germany, 13509
    • Withdrawn
    • Vivantes Humboldt Klinikum
  • Bielefeld, Germany, 33604
    • Recruiting
    • Klinikum Bielefeld
  • Coburg, Germany, 96450
    • Recruiting
    • Regiomed Klinikum Coburg
  • Cottbus, Germany, 03048
    • Recruiting
    • Carl-Thiem-Klinikum
  • Dresden, Germany, 01067
    • Recruiting
    • Städtisches Klinikum Dresden
  • Dresden, Germany, 01307
    • Recruiting
    • Technische Universität Dresden - Herzzentrum Dresden
  • Essen, Germany, 45138
    • Recruiting
    • Elisabeth-Krankenhaus Essen
  • Greifswald, Germany, 17475
    • Recruiting
    • Universitätsmedizin Greifswald
  • Göttingen, Germany, 37075
    • Recruiting
    • Georg-August-Universität Göttingen - Universitätsmedizin Göttingen
  • Gütersloh, Germany, 33332
    • Recruiting
    • Klinikum Gütersloh
  • Hamburg, Germany, 21075
    • Recruiting
    • Asklepios Klinikum Harburg
  • Hamburg, Germany, 22457
    • Recruiting
    • Albertinen Herz- und Gefäßzentrum
  • Hamburg, Germany, 20099
    • Recruiting
    • Asklepios Kliniken Hamburg
  • Jena, Germany, 07747
    • Recruiting
    • Universitätsklinikum Jena
  • Kaiserslautern, Germany, 67655
    • Recruiting
    • Westpfalz-Klinikum GmbH
  • Karlsruhe, Germany, 76133
    • Recruiting
    • Stadtisches Klinikum Karlsruhe
  • Kassel, Germany, 34121
    • Recruiting
    • B.Braun Ambulantes Herzzentrum Kassel
  • Langen, Germany, 63225
    • Recruiting
    • Asklepios Kliniken Langen
  • Leipzig, Germany, 04103
    • Recruiting
    • Universitätsklinikum Leipzig
  • Leipzig, Germany, 04289
    • Recruiting
    • Herzzentrum Leipzig
  • Leipzig, Germany, 04129
    • Recruiting
    • Klinikum St. Georg
  • Lübeck, Germany, 23538
    • Recruiting
    • Universitatsklinikum Schleswig-Holstein
  • Minden, Germany, 32429
    • Recruiting
    • Johannes Wesling Klinikum
  • München, Germany, 81377
    • Recruiting
    • Klinikum der Ludwig-Maximilians-Universität München (LMU Klinikum)
  • Neumünster, Germany, 24534
    • Recruiting
    • FEK - Friedrich-Ebert-Krankenhaus Neumünster
  • Rothenburg upon Tauber, Germany, 91541
    • Recruiting
    • Klinik Rothenburg ANregiomed
  • Wuppertal, Germany, 42117
    • Recruiting
    • Helios Universitätsklinikum Wuppertal
• Hungary
  • Budapest, Hungary, 1085
    • Recruiting
    • Semmelweis University
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus
• Martinique
  • Fort-de-France Cedex, Martinique, 97261
    • Recruiting
    • Le Centre Hospitalier Universitaire de Martinique
• Netherlands
  • Amsterdam, Netherlands, 1105
    • Recruiting
    • Amsterdam UMC
  • Eindhoven, Netherlands, 5623
    • Recruiting
    • Stichting Catharina Ziekenhuis
  • Enschede, Netherlands, 7512 KZ
    • Recruiting
    • Medisch Spectrum Twente
  • Groningen, Netherlands, 9700
    • Recruiting
    • Universitair Medisch Center Groningen
  • Maastricht, Netherlands, 6229
    • Recruiting
    • Maastricht University Medical Center
• Poland
  • Rzeszów, Poland, 35-301
    • Recruiting
    • Kliniczny Szpital Wojewódzki Nr 2 im.Św.Jadwigi Królowej w Rzeszowie
  • Warsaw, Poland, 04-141
    • Recruiting
    • Wojskowy Instytut Medyczny
  • Zabrze, Poland, 41-800
    • Recruiting
    • Slaskie Centrum Chorob Serca W Zabrzu
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Hospital General Universitario de Alicante
  • Madrid, Spain, 28046
    • Recruiting
    • La Paz University Hospital
  • Madrid, Spain, 28041
    • Recruiting
    • Instituto de Investigación Hospital 12 de Octubre
  • Murcia, Spain, 30120
    • Recruiting
    • Hospital Universitario Virgen de La Arrixaca
• United Kingdom
  • Halifax, United Kingdom, HX3 0PW
    • Recruiting
    • Calderdale Royal Hospital
  • Leeds, United Kingdom, LS9 7TF
    • Recruiting
    • The Leeds Teaching Hospitals NHS Trust - St James's University Hospital
  • Margate, United Kingdom, CT9 4AN
    • Recruiting
    • Queen Elizabeth The Queen Mother Hospital Margate
  • Nuneaton, United Kingdom, CV10 7DJ
    • Recruiting
    • George Eliot Hospital
  • Salisbury, United Kingdom, SP2 8BJ
    • Recruiting
    • Salisbury District Hospital
  • Stockton-on-Tees, United Kingdom, TS19 8PE
    • Recruiting
    • University Hospital of North Tees

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).
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 if study-specific treatment is still active at enrolment into PROFID EHRA.
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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Optimal Medical Therapy with ICD device therapy; 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	Device: Implantable cardioverter-defibrillator (ICD); 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.; Drug: Optimal Medical Therapy (OMT); Patients will be treated according to Optimal Medical Therapy defined by the following guidelines: 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes; 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure
Experimental: Optimal Medical Therapy without ICD device therapy; 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	Drug: Optimal Medical Therapy (OMT); Patients will be treated according to Optimal Medical Therapy defined by the following guidelines: 2019 ESC guidelines for the diagnosis and management of chronic coronary syndromes; 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from randomisation to death from cardiovascular causes	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 sudden cardiac death	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 first hospital readmissions for cardiovascular causes after date of randomisation	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
Average length of stay in hospital during the study period	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
Quality of life (EQ-5D-5L) trajectories over time	Quality of life (EQ-5D-5L) trajectories over time	At baseline and 12-month intervals thereafter

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: Leipzig Heart Science gGmbH
• Investigators: Principal Investigator: Gerhard Hindricks, Prof, Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine; Principal Investigator: Nikolaos Dagres, MD, Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine

Publications and helpful links

General Publications

• Qian Y, Roque CR, Woods B, Iglesias Urrutia CP, Gc VS, Gur Arie M, Fischer D, Dagres N, Hindricks G, Manca A. Economic evaluation protocol for the PRevention Of sudden cardiac death aFter myocardial Infarction by Defibrillator implantation: the PROFID EHRA trial. BMJ Open. 2026 Jan 8;16(1):e097495. doi: 10.1136/bmjopen-2024-097495.
• Dagres N, Gale CP, Nadarajah R, Boveda S, Merino JL, Nielsen JC, Kirchhof P, Kutyifa V, Taborsky M, Thiele H, Tijssen JGP, Verma A, De Potter T, Braunschweig F, Merkely B, Sommer P, Vernooy K, Suleiman M, Purerfellner H, Hindricks G; PROFID EHRA trial investigators. PRevention of sudden cardiac death aFter myocardial infarction by defibrillator implantation: Design and rationale of the PROFID EHRA randomized clinical trial. Am Heart J. 2026 Jan;291:37-43. doi: 10.1016/j.ahj.2025.07.071. Epub 2025 Aug 6.

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2023
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027

Study Registration Dates

• First Submitted: December 19, 2022
• First Submitted That Met QC Criteria: December 19, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Myocardial Infarction; Sudden Cardiac Death; Implantable Cardioverter Defibrillator
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Death; Infarction; Necrosis; Myocardial Ischemia; Ischemia; Heart Arrest; Death, Sudden; Pathological Conditions, Signs and Symptoms; Death, Sudden, Cardiac; Myocardial Infarction; Equipment and Supplies; Defibrillators; Electrodes; Electrical Equipment and Supplies; Electrodes, Implanted; Prostheses and Implants; Defibrillators, Implantable
• Other Study ID Numbers: LHS-2019-0209

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No