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Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation (PROFID EHRA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05665608
Recruitment Status : Recruiting
First Posted : December 27, 2022
Last Update Posted : April 16, 2024
Sponsor:
Information provided by (Responsible Party):
Daniela Fischer, Charite University, Berlin, Germany

Tracking Information
First Submitted Date  ICMJE December 19, 2022
First Posted Date  ICMJE December 27, 2022
Last Update Posted Date April 16, 2024
Actual Study Start Date  ICMJE November 16, 2023
Estimated Primary Completion Date April 30, 2027   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 19, 2022)
Time from randomisation to the occurrence of all-cause death. [ Time Frame: event-driven, expected about 15 months after last patient in ]
Randomization to end of study
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 19, 2022)
  • Time from randomisation to death from cardiovascular causes [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: At baseline and 6-month intervals thereafter ]
    Quality of life (EQ-5D-5L) trajectories over time
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation
Official Title  ICMJE Prevention Of Sudden Cardiac Death After Myocardial Infarction by Defibrillator Implantation
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE 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)
Masking: None (Open Label)
Masking Description:
The PROFID EHRA trial is an open-label, blinded outcome assessment study. Thus, unblinding procedures for investigators are not applicable.
Primary Purpose: Prevention
Condition  ICMJE
  • Sudden Cardiac Death
  • Myocardial Infarction
Intervention  ICMJE
  • 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:

    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
Study Arms  ICMJE
  • 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
    Interventions:
    • Device: Implantable cardioverter-defibrillator (ICD)
    • Drug: Optimal Medical Therapy (OMT)
  • 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
    Intervention: Drug: Optimal Medical Therapy (OMT)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 6, 2023)
3595
Original Estimated Enrollment  ICMJE
 (submitted: December 19, 2022)
1778
Estimated Study Completion Date  ICMJE April 30, 2027
Estimated Primary Completion Date April 30, 2027   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Gerhard Hindricks, Prof +49 30 450 513211 Gerhard.Hindricks@dhzc-charite.de
Contact: Nikolaos Dagres, MD +49 30 450 665407 Nikolaos.Dagres@dhzc-charite.de
Listed Location Countries  ICMJE Austria,   Czechia,   Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05665608
Other Study ID Numbers  ICMJE LHS-2019-0209
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Daniela Fischer, Charite University, Berlin, Germany
Original Responsible Party Helios Health Institute GmbH
Current Study Sponsor  ICMJE Charite University, Berlin, Germany
Original Study Sponsor  ICMJE Helios Health Institute GmbH
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: 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
PRS Account Charite University, Berlin, Germany
Verification Date April 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP