Clinical trial NCT05665608: Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation
Official title: Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sudden Cardiac Death
Myocardial Infarction
Keywords: Implantable Cardioverter Defibrillator
Sudden Cardiac Death
Myocardial Infarction
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2022-12-27
Enrollment: 3595
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: PREVENTION

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Time from randomisation to the occurrence of all-cause death.
timeFrame: event-driven, expected about 15 months after last patient in
Secondary outcomes:
measure: Time from randomisation to death from cardiovascular causes
timeFrame: Randomization to end of study (event-driven, expected about 15 months after last patient in
measure: Time from randomisation to sudden cardiac death
timeFrame: Randomization to end of study (event-driven, expected about 15 months after last patient in
measure: Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation
timeFrame: Randomization to end of study (event-driven, expected about 15 months after last patient in
measure: Average length of stay in hospital during the study period
timeFrame: Randomization to end of study (event-driven, expected about 15 months after last patient in
measure: Quality of life (EQ-5D-5L) trajectories over time
timeFrame: At baseline and 12-month intervals thereafter
Other outcomes:
Locations:
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
city: Innsbruck
country: Austria
facility: Tirol Kliniken - Universitätsklinik Innsbruck
city: Klagenfurt am Wörthersee
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg - Universitätsklinikum der PMU
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
city: Wiener Neustadt
country: Austria
facility: Universitätsklinikum Wiener Neustadt
city: Aalst
country: Belgium
facility: OLV Ziekenhuis Campus Aalst
city: Brugge
country: Belgium
facility: AZ Sint-Jan Brugge-Campus Sint-Jan
city: Liège
country: Belgium
facility: Centre hospitaliser régional (CHR) de la Citadelle
city: Yvoir
country: Belgium
facility: Centre Hospitalier Universitaire CHU UCL Namur - Site Godinne
city: Olomouc
country: Czechia
facility: Fakultní Nemocnice Olomouc
city: Aarhus
country: Denmark
facility: Aarhus University Hospital I
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Grenoble
country: France
facility: University Hospital Grenoble-Alpes
city: Rennes
country: France
facility: Chu de Rennes
city: Toulouse
country: France
facility: Clinique Pasteur
city: Ahaus
country: Germany
facility: St. Marien-Krankenhaus - Klinikum Westmünsterland
city: Aue
country: Germany
facility: Helios Klinikum Aue
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik Bad Nauheim
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum NRW Universitätsklinik der Ruhr-Universität Bochum
city: Bad Segeberg
country: Germany
facility: Segeberger Kliniken Gmbh
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CCM)
city: Berlin
country: Germany
facility: Sana Klinikum Lichtenberg
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CBF)
city: Berlin
country: Germany
facility: BG Klinikum Unfallkrankenhaus Berlin
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin (CVK)
city: Berlin
country: Germany
facility: Vivantes Humboldt Klinikum
city: Bielefeld
country: Germany
facility: Klinikum Bielefeld
city: Coburg
country: Germany
facility: REGIOMED Klinikum Coburg
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum
city: Dresden
country: Germany
facility: Städtisches Klinikum Dresden
city: Dresden
country: Germany
facility: Technische Universität Dresden - Herzzentrum Dresden
city: Essen
country: Germany
facility: Elisabeth-Krankenhaus Essen
city: Greifswald
country: Germany
facility: Universitätsmedizin Greifswald
city: Göttingen
country: Germany
facility: Georg-August-Universität Göttingen - Universitätsmedizin Göttingen
city: Gütersloh
country: Germany
facility: Klinikum Gütersloh
city: Hamburg
country: Germany
facility: Asklepios Kliniken Hamburg
city: Hamburg
country: Germany
facility: Asklepios Klinikum Harburg
city: Hamburg
country: Germany
facility: Albertinen Herz- und Gefäßzentrum
city: Jena
country: Germany
facility: Universitätsklinikum Jena
city: Kaiserslautern
country: Germany
facility: Westpfalz-Klinikum GmbH
city: Karlsruhe
country: Germany
facility: Städtisches Klinikum Karlsruhe
city: Langen
country: Germany
facility: Asklepios Kliniken Langen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Leipzig
country: Germany
facility: Klinikum St. Georg
city: Leipzig
country: Germany
facility: Herzzentrum Leipzig
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: Minden
country: Germany
facility: Johannes Wesling Klinikum
city: Rothenburg ob der Tauber
country: Germany
facility: Klinik Rothenburg ANregiomed
city: Wuppertal
country: Germany
facility: Helios Universitätsklinikum Wuppertal
city: Budapest
country: Hungary
facility: Semmelweis University
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Eindhoven
country: Netherlands
facility: Stichting Catharina Ziekenhuis
city: Groningen
country: Netherlands
facility: Universitair Medisch Center Groningen
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Rzeszów
country: Poland
facility: Kliniczny Szpital Wojewódzki Nr 2 im.Św.Jadwigi Królowej w Rzeszowie
city: Warsaw
country: Poland
facility: Wojskowy Instytut Medyczny
city: Zabrze
country: Poland
facility: Śląskie Centrum Chorób Serca w Zabrzu
city: Madrid
country: Spain
facility: La Paz University Hospital
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
Study officials:
affiliation: Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine
name: Gerhard Hindricks, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Deutsches Herzzentrum der Charité, Department of Cardiology, Angiology and Intensive Care Medicine
name: Nikolaos Dagres, MD
role: PRINCIPAL_INVESTIGATOR
References: