Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

NCT ID: NCT05665608

Last Updated: 2025-10-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

3595 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-16

Study Completion Date

2027-11-30

Brief Summary

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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

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Conditions

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Sudden Cardiac Death Myocardial Infarction

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

The PROFID EHRA trial is an open-label, blinded outcome assessment study. Thus, unblinding procedures for investigators are not applicable.

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Implantable cardioverter-defibrillator (ICD)

Intervention Type 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)

Intervention Type 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 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

Group Type EXPERIMENTAL

Optimal Medical Therapy (OMT)

Intervention Type 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

Interventions

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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.

Intervention Type DEVICE

Optimal Medical Therapy (OMT)

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Charite University, Berlin, Germany

OTHER

Sponsor Role lead

Responsible Party

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Daniela Fischer

Project Manager

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Gerhard Hindricks, Prof

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine

Nikolaos Dagres, MD

Role: PRINCIPAL_INVESTIGATOR

Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine

Locations

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Landeskrankenhaus Feldkirch

Feldkirch, , Austria

Site Status RECRUITING

LKH Universitätsklinikum Graz

Graz, , Austria

Site Status RECRUITING

Tirol Kliniken - Universitätsklinik Innsbruck

Innsbruck, , Austria

Site Status RECRUITING

Klinikum Klagenfurt am Wörthersee

Klagenfurt, , Austria

Site Status RECRUITING

Ordensklinikum Linz GmbH Elisabethinen

Linz, , Austria

Site Status RECRUITING

Landeskrankenhaus Salzburg - Universitätsklinikum der PMU

Salzburg, , Austria

Site Status RECRUITING

Universitätsklinikum St. Pölten

Sankt Pölten, , Austria

Site Status RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, , Austria

Site Status RECRUITING

Universitätsklinikum Wiener Neustadt

Wiener Neustadt, , Austria

Site Status RECRUITING

OLV Ziekenhuis Campus Aalst

Aalst, , Belgium

Site Status RECRUITING

AZ Sint-Jan Brugge-Campus Sint-Jan

Bruges, , Belgium

Site Status RECRUITING

Centre hospitaliser régional (CHR) de la Citadelle

Liège, , Belgium

Site Status RECRUITING

Centre Hospitalier Universitaire CHU UCL Namur - Site Godinne

Yvoir, , Belgium

Site Status RECRUITING

Fakultní Nemocnice Olomouc

Olomouc, , Czechia

Site Status RECRUITING

Všeobecná Fakultní Nemocnice v Praze

Prague, , Czechia

Site Status RECRUITING

Institut Klinické a Experimentální Medicíny

Prague, , Czechia

Site Status RECRUITING

Masaryk Hospital

Ústí nad Labem, , Czechia

Site Status RECRUITING

Aarhus University Hospital I

Aarhus, , Denmark

Site Status RECRUITING

CHU Amiens Picardie

Amiens, , France

Site Status RECRUITING

CHU Henri Mondor

Créteil, , France

Site Status RECRUITING

University Hospital Grenoble-Alpes

Grenoble, , France

Site Status RECRUITING

Européen Georges Pompidou Hospital Paris

Paris, , France

Site Status RECRUITING

Chu de Rennes

Rennes, , France

Site Status RECRUITING

Centre Cardiologique du Nord

Saint-Denis, , France

Site Status RECRUITING

University Hospital Rangueil Toulouse

Toulouse, , France

Site Status RECRUITING

Clinique Pasteur

Toulouse, , France

Site Status RECRUITING

St. Marien-Krankenhaus - Klinikum Westmünsterland

Ahaus, , Germany

Site Status RECRUITING

Helios Klinikum Aue

Aue, , Germany

Site Status RECRUITING

Kerckhoff-Klinik Bad Nauheim

Bad Nauheim, , Germany

Site Status RECRUITING

Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum

Bad Oeynhausen, , Germany

Site Status RECRUITING

Segeberger Kliniken Gmbh

Bad Segeberg, , Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin (CCM)

Berlin, , Germany

Site Status RECRUITING

Sana Klinikum Lichtenberg

Berlin, , Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin (CBF)

Berlin, , Germany

Site Status RECRUITING

BG Klinikum Unfallkrankenhaus Berlin

Berlin, , Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin (CVK)

Berlin, , Germany

Site Status RECRUITING

Vivantes Humboldt Klinikum

Berlin, , Germany

Site Status RECRUITING

Klinikum Bielefeld

Bielefeld, , Germany

Site Status RECRUITING

REGIOMED Klinikum Coburg

Coburg, , Germany

Site Status RECRUITING

Carl-Thiem-Klinikum

Cottbus, , Germany

Site Status RECRUITING

Städtisches Klinikum Dresden

Dresden, , Germany

Site Status RECRUITING

Technische Universität Dresden - Herzzentrum Dresden

Dresden, , Germany

Site Status RECRUITING

Elisabeth-Krankenhaus Essen

Essen, , Germany

Site Status RECRUITING

Georg-August-Universität Göttingen - Universitätsmedizin Göttingen

Göttingen, , Germany

Site Status RECRUITING

Universitätsmedizin Greifswald

Greifswald, , Germany

Site Status RECRUITING

Klinikum Gütersloh

Gütersloh, , Germany

Site Status RECRUITING

Asklepios Kliniken Hamburg

Hamburg, , Germany

Site Status RECRUITING

Asklepios Klinikum Harburg

Hamburg, , Germany

Site Status RECRUITING

Albertinen Herz- und Gefäßzentrum

Hamburg, , Germany

Site Status RECRUITING

Universitätsklinikum Jena

Jena, , Germany

Site Status RECRUITING

Westpfalz-Klinikum GmbH

Kaiserslautern, , Germany

Site Status RECRUITING

Städtisches Klinikum Karlsruhe

Karlsruhe, , Germany

Site Status RECRUITING

Asklepios Kliniken Langen

Langen, , Germany

Site Status RECRUITING

Universitätsklinikum Leipzig

Leipzig, , Germany

Site Status RECRUITING

Klinikum St. Georg

Leipzig, , Germany

Site Status RECRUITING

Herzzentrum Leipzig

Leipzig, , Germany

Site Status RECRUITING

Universitätsklinikum Schleswig-Holstein

Lübeck, , Germany

Site Status RECRUITING

Johannes Wesling Klinikum

Minden, , Germany

Site Status RECRUITING

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

München, , Germany

Site Status RECRUITING

FEK - Friedrich-Ebert-Krankenhaus Neumünster

Neumünster, , Germany

Site Status RECRUITING

Klinik Rothenburg ANregiomed

Rothenburg upon Tauber, , Germany

Site Status RECRUITING

Helios Universitätsklinikum Wuppertal

Wuppertal, , Germany

Site Status RECRUITING

Semmelweis University

Budapest, , Hungary

Site Status RECRUITING

Rambam Health Care Campus

Haifa, , Israel

Site Status RECRUITING

Amsterdam UMC

Amsterdam, , Netherlands

Site Status RECRUITING

Stichting Catharina Ziekenhuis

Eindhoven, , Netherlands

Site Status RECRUITING

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status RECRUITING

Universitair Medisch Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Maastricht University Medical Center

Maastricht, , Netherlands

Site Status RECRUITING

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

Rzeszów, , Poland

Site Status RECRUITING

Wojskowy Instytut Medyczny

Warsaw, , Poland

Site Status RECRUITING

Śląskie Centrum Chorób Serca w Zabrzu

Zabrze, , Poland

Site Status RECRUITING

Hospital General Universitario de Alicante

Alicante, , Spain

Site Status RECRUITING

La Paz University Hospital

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de la Arrixaca

Murcia, , Spain

Site Status RECRUITING

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

Leeds, , United Kingdom

Site Status RECRUITING

Queen Elizabeth The Queen Mother Hospital Margate

Margate, , United Kingdom

Site Status RECRUITING

George Eliot Hospital

Nuneaton, , United Kingdom

Site Status RECRUITING

University Hospital of North Tees

Stockton-on-Tees, , United Kingdom

Site Status RECRUITING

Countries

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Austria Belgium Czechia Denmark France Germany Hungary Israel Netherlands Poland Spain United Kingdom

Central Contacts

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Gerhard Hindricks, Prof

Role: CONTACT

+49 30 450 513211

Nikolaos Dagres, MD

Role: CONTACT

+49 30 450 665407

References

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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.

Reference Type DERIVED
PMID: 40774643 (View on PubMed)

Other Identifiers

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LHS-2019-0209

Identifier Type: -

Identifier Source: org_study_id

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