Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

NCT05665608 | Recruiting DMC

• 1 other identifier: LHS-2019-0209
• Study Type: interventional
• Target: 3,595
• Locations: 13 countries
• Sites: 86

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.

Conditions

Sudden Cardiac Death; Myocardial Infarction

Keywords

Implantable Cardioverter Defibrillator; Sudden Cardiac Death; Myocardial Infarction

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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

  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

  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

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

• Quality of life (EQ-5D-5L) trajectories over time

  At baseline and 12-month intervals thereafter

Study Arms (2)

Optimal Medical Therapy with ICD device therapy

ACTIVE COMPARATOR

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); Drug: Optimal Medical Therapy (OMT)

Optimal Medical Therapy without ICD device therapy

EXPERIMENTAL

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)

Interventions

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

Optimal Medical Therapy with ICD device therapy; Optimal Medical Therapy without ICD device therapy

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 with ICD device therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• On OMT for at least 3 months prior to enrolment.
• LVEF ≤ 35% (at transthoracic echocardiography or cardiac magnetic resonance imaging \[MRI\] at least 3 months after MI).
• Signed informed consent.

You may not qualify if:

• 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)
• Foreseable violation of instruction for use (IFU) of the ICD device selected for implantation (valid for control group patients, only).
• Acute coronary syndrome or coronary angioplasty or coronary artery bypass grafting performed within 6 weeks prior to enrolment.
• Cardiac valve surgery or percutaneous cardiac valvular intervention performed within 6 weeks prior to enrolment.
• 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.
• Any known disease that limits life expectancy to less than 1 year.
• Participation in another randomised clinical trial if study-specific treatment is still active at enrolment into PROFID EHRA.
• 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.

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead

Study Sites (86)

Landeskrankenhaus Feldkirch

Feldkirch, 6800, Austria

RECRUITING

LKH Universitätsklinikum Graz

Graz, 8036, Austria

RECRUITING

Tirol Kliniken - Universitätsklinik Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Klinikum Klagenfurt am Wörthersee

Klagenfurt, 9020, Austria

RECRUITING

Ordensklinikum Linz GmbH Elisabethinen

Linz, 4020, Austria

RECRUITING

Landeskrankenhaus Salzburg - Universitätsklinikum der PMU

Salzburg, 5020, Austria

RECRUITING

Universitätsklinikum St. Pölten

Sankt Pölten, 3100, Austria

RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, 4600, Austria

RECRUITING

Universitätsklinikum Wiener Neustadt

Wiener Neustadt, 2700, Austria

RECRUITING

OLV Ziekenhuis Campus Aalst

Aalst, 9300, Belgium

RECRUITING

AZ Sint-Jan Brugge-Campus Sint-Jan

Bruges, 8000, Belgium

RECRUITING

Centre hospitaliser régional (CHR) de la Citadelle

Liège, 4000, Belgium

RECRUITING

Centre Hospitalier Universitaire CHU UCL Namur - Site Godinne

Yvoir, 5530, Belgium

RECRUITING

Fakultní Nemocnice Olomouc

Olomouc, 779 00, Czechia

TERMINATED

Všeobecná Fakultní Nemocnice v Praze

Prague, 128 08, Czechia

RECRUITING

Institut Klinické a Experimentální Medicíny

Prague, 140 21, Czechia

RECRUITING

Masaryk Hospital

Ústí nad Labem, 400 11, Czechia

RECRUITING

Aarhus University Hospital I

Aarhus, 8200, Denmark

RECRUITING

CHU Amiens Picardie

Amiens, 80054, France

RECRUITING

Hôpital de la Cavale Blanche-CHU BREST

Brest, 29609, France

RECRUITING

CHU Henri Mondor

Créteil, 94010, France

RECRUITING

University Hospital Grenoble-Alpes

Grenoble, 38700, France

RECRUITING

Européen Georges Pompidou Hospital Paris

Paris, 75015, France

RECRUITING

Hôpital Bichat Claude Bernard

Paris, 75018, France

RECRUITING

Chu de Rennes

Rennes, 35000, France

RECRUITING

Centre Cardiologique du Nord

Saint-Denis, 93200, France

RECRUITING

University Hospital Rangueil Toulouse

Toulouse, 31059, France

RECRUITING

Clinique Pasteur

Toulouse, 31076, France

RECRUITING

St. Marien-Krankenhaus - Klinikum Westmünsterland

Ahaus, 48683, Germany

WITHDRAWN

Helios Klinikum Aue

Aue, 08280, Germany

RECRUITING

Kerckhoff-Klinik Bad Nauheim

Bad Nauheim, 61231, Germany

RECRUITING

Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum

Bad Oeynhausen, 32545, Germany

RECRUITING

Segeberger Kliniken Gmbh

Bad Segeberg, 23795, Germany

RECRUITING

Charité - Universitätsmedizin Berlin (CCM)

Berlin, 10117, Germany

RECRUITING

Sana Klinikum Lichtenberg

Berlin, 10365, Germany

RECRUITING

Charité - Universitätsmedizin Berlin (CBF)

Berlin, 12203, Germany

RECRUITING

BG Klinikum Unfallkrankenhaus Berlin

Berlin, 12683, Germany

RECRUITING

Charité - Universitätsmedizin Berlin (CVK)

Berlin, 13353, Germany

RECRUITING

Vivantes Humboldt Klinikum

Berlin, 13509, Germany

WITHDRAWN

Klinikum Bielefeld

Bielefeld, 33604, Germany

RECRUITING

REGIOMED Klinikum Coburg

Coburg, 96450, Germany

RECRUITING

Carl-Thiem-Klinikum

Cottbus, 03048, Germany

RECRUITING

Städtisches Klinikum Dresden

Dresden, 01067, Germany

RECRUITING

Technische Universität Dresden - Herzzentrum Dresden

Dresden, 01307, Germany

RECRUITING

Elisabeth-Krankenhaus Essen

Essen, 45138, Germany

RECRUITING

Georg-August-Universität Göttingen - Universitätsmedizin Göttingen

Göttingen, 37075, Germany

RECRUITING

Universitätsmedizin Greifswald

Greifswald, 17475, Germany

RECRUITING

Klinikum Gütersloh

Gütersloh, 33332, Germany

RECRUITING

Asklepios Kliniken Hamburg

Hamburg, 20099, Germany

RECRUITING

Asklepios Klinikum Harburg

Hamburg, 21075, Germany

RECRUITING

Albertinen Herz- und Gefäßzentrum

Hamburg, 22457, Germany

RECRUITING

Universitätsklinikum Jena

Jena, 07747, Germany

RECRUITING

Westpfalz-Klinikum GmbH

Kaiserslautern, 67655, Germany

RECRUITING

Städtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

RECRUITING

B.Braun Ambulantes Herzzentrum Kassel

Kassel, 34121, Germany

RECRUITING

Asklepios Kliniken Langen

Langen, 63225, Germany

RECRUITING

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

RECRUITING

Klinikum St. Georg

Leipzig, 04129, Germany

RECRUITING

Herzzentrum Leipzig

Leipzig, 04289, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

RECRUITING

Johannes Wesling Klinikum

Minden, 32429, Germany

RECRUITING

Klinikum der Ludwig-Maximilians-Universität München (LMU Klinikum)

München, 81377, Germany

RECRUITING

FEK - Friedrich-Ebert-Krankenhaus Neumünster

Neumünster, 24534, Germany

RECRUITING

Klinik Rothenburg ANregiomed

Rothenburg upon Tauber, 91541, Germany

RECRUITING

Helios Universitätsklinikum Wuppertal

Wuppertal, 42117, Germany

RECRUITING

Semmelweis University

Budapest, 1085, Hungary

RECRUITING

Rambam Health Care Campus

Haifa, 3109601, Israel

RECRUITING

Le Centre Hospitalier Universitaire de Martinique

Fort-de-France Cedex, 97261, Martinique

RECRUITING

Amsterdam UMC

Amsterdam, 1105, Netherlands

RECRUITING

Stichting Catharina Ziekenhuis

Eindhoven, 5623, Netherlands

RECRUITING

Medisch Spectrum Twente

Enschede, 7512 KZ, Netherlands

RECRUITING

Universitair Medisch Center Groningen

Groningen, 9700, Netherlands

RECRUITING

Maastricht University Medical Center

Maastricht, 6229, Netherlands

RECRUITING

Kliniczny Szpital Wojewódzki Nr 2 im.Św.Jadwigi Królowej w Rzeszowie

Rzeszów, 35-301, Poland

RECRUITING

Wojskowy Instytut Medyczny

Warsaw, 04-141, Poland

RECRUITING

Śląskie Centrum Chorób Serca w Zabrzu

Zabrze, 41-800, Poland

RECRUITING

Hospital General Universitario de Alicante

Alicante, 03010, Spain

RECRUITING

Instituto de Investigación Hospital 12 de Octubre

Madrid, 28041, Spain

RECRUITING

La Paz University Hospital

Madrid, 28046, Spain

RECRUITING

Hospital Universitario Virgen de la Arrixaca

Murcia, 30120, Spain

RECRUITING

Calderdale Royal Hospital

Halifax, HX3 0PW, United Kingdom

RECRUITING

The Leeds Teaching Hospitals NHS Trust - St James's University Hospital

Leeds, LS9 7TF, United Kingdom

RECRUITING

Queen Elizabeth The Queen Mother Hospital Margate

Margate, CT9 4AN, United Kingdom

RECRUITING

George Eliot Hospital

Nuneaton, CV10 7DJ, United Kingdom

RECRUITING

Salisbury District Hospital

Salisbury, SP2 8BJ, United Kingdom

RECRUITING

University Hospital of North Tees

Stockton-on-Tees, TS19 8PE, United Kingdom

RECRUITING

Related Publications (2)

• 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.

  PMID: 41506764 DERIVED

• 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.

  PMID: 40774643 DERIVED

MeSH Terms

Conditions

Death, Sudden, Cardiac; Myocardial Infarction

Interventions

Defibrillators, Implantable

Condition Hierarchy (Ancestors)

Heart Arrest; Heart Diseases; Cardiovascular Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Myocardial Ischemia; Vascular Diseases; Infarction; Ischemia; Necrosis

Intervention Hierarchy (Ancestors)

Defibrillators; Electrodes; Electrical Equipment and Supplies; Equipment and Supplies; Electrodes, Implanted; Prostheses and Implants

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gerhard Hindricks, Prof

CONTACT

+49 30 450 513211; Gerhard.Hindricks@dhzc-charite.de

Nikolaos Dagres, MD

CONTACT

+49 30 450 665407; Nikolaos.Dagres@dhzc-charite.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The PROFID EHRA trial is an open-label, blinded outcome assessment study. Thus, unblinding procedures for investigators are not applicable.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Project Manager

Model Details: An investigator-driven, prospective, parallel-group, randomised, open, blinded outcome assessment (PROBE), multi-centre, non-inferiority trial without investigational medical products (Proof of Strategy Trial)

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: December 27, 2022
• Study Start: November 16, 2023
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

ES (4); HU (1); IL (1); PL (3); AU (9); CZ (4); BE (4); DE (37); FR (10); NL (5); DK (1); GB (6); MA (1)