PROFID: Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

Sponsor

Leipzig Heart Institute GmbH (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05665608

Collaborator

Leipzig Heart Science gGmbH (Other)

1,778

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Sudden Cardiac Death Myocardial Infarction	Device: Implantable cardioverter-defibrillator (ICD) Drug: Optimal Medical Therapy (OMT)	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1778 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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)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)

Masking:

None (Open Label)

Masking Description:

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

Primary Purpose:

Prevention

Official Title:

Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Sep 30, 2025

Anticipated Study Completion Date :

Jan 31, 2027

Arms and Interventions

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

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)

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 death from cardiovascular causes
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 sudden cardiac death
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]
Time from randomisation to first hospital readmissions for cardiovascular causes after date of randomisation
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]
Average length of stay in hospital during the study period
Quality of life (EQ-5D-5L) trajectories over time [At baseline and 6-month intervals thereafter]
Quality of life (EQ-5D-5L) trajectories over time

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 and at least 3 months prior to enrolment.
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:

Class I or IIa indication for implantation of an ICD for secondary prevention of SCD and ventricular tachycardia (according to the 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of SCD, see Appendix V).
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) (according to the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy, see Appendix VI and 0)
Violation of instruction for use (IFU) of the ICD device selected for implantation (valid for control group patients, only).
Hospitalised with unstable heart failure with NYHA class IV within 6 weeks prior to enrolment.
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.
Any known disease that limits life expectancy to less than 1 year.
Participation in another randomised clinical trial, either within the 3 months prior to enrolment or still on-going (participation in sub-studies connected to this trial is permitted).
Previous participation in PROFID.
Drug abuse or clinically manifest alcohol abuse.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Leipzig Heart Institute GmbH
Leipzig Heart Science gGmbH

Investigators

Principal Investigator: Gerhard Hindricks, MD, Department of Electrophysiology, Leipzig Heart Center at University of Leipzig
Principal Investigator: Nikolaos Dagres, MD, Department of Electrophysiology, Leipzig Heart Center at University of Leipzig