Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

Myocardial Infarction Clinical Trial

— PROFID EHRA  

Official title:

Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05665608
• Other study ID #: LHS-2019-0209
• Status: Recruiting
• Phase: N/A
• Start date: November 16, 2023
• Est. completion date: April 30, 2027

Study information

• Verified date: June 2024
• Source: Charite University, Berlin, Germany
• Contact: Gerhard Hindricks, Prof
• Phone: +49 30 450 513211
• Email: Gerhard.Hindricks[@]dhzc-charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 3595
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Death
• Death, Sudden, Cardiac
• Infarction
• Myocardial Infarction
• Sudden Cardiac Death

Intervention

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

Locations

Country	Name	City	State
Austria	Tirol Kliniken - Universitätsklinik Innsbruck	Innsbruck
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz
Czechia	Fakultní Nemocnice Olomouc	Olomouc
Germany	St. Marien-Krankenhaus - Klinikum Westmünsterland	Ahaus
Germany	Helios Klinikum Aue	Aue
Germany	Segeberger Kliniken Gmbh	Bad Segeberg
Germany	Charité - Universitätsmedizin Berlin (CBF)	Berlin
Germany	Charité - Universitätsmedizin Berlin (CVK)	Berlin
Germany	Sana Klinikum Lichtenberg	Berlin
Germany	Vivantes Humboldt Klinikum	Berlin
Germany	REGIOMED Klinikum Coburg	Coburg
Germany	Carl-Thiem-Klinikum	Cottbus
Germany	Klinikum Gütersloh	Gütersloh
Germany	Albertinen Herz- und Gefäßzentrum	Hamburg
Germany	Asklepios Kliniken Hamburg	Hamburg
Germany	Asklepios Klinikum Harburg	Hamburg
Germany	Universitätsklinikum Jena	Jena
Germany	Städtisches Klinikum Karlsruhe	Karlsruhe
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Universitätsklinikum Schleswig-Holstein	Lübeck
Germany	Klinik Rothenburg ANregiomed	Rothenburg ob der Tauber
Germany	Helios Universitätsklinikum Wuppertal	Wuppertal

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Countries where clinical trial is conducted

Austria,  Czechia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Quality of life (EQ-5D-5L) trajectories over time	Quality of life (EQ-5D-5L) trajectories over time	At baseline and 6-month intervals thereafter