Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias Following Acute Myocardial Infarction (PROTECT-ICD)
PROTECT-ICD
2 other identifiers
interventional
1,058
15 countries
52
Brief Summary
The PROTECT-ICD trial is a physician-led, multi-centre randomised controlled trial targeting prevention of sudden cardiac death in patients who have poor cardiac function following a myocardial infarct (MI). The trial aims to assess the role of electrophysiology study (EPS) in guiding implantable cardioverter-defibrillator (ICD) implantation, in patients early following MI (first 40 days). The secondary aim is to assess the utility of cardiac MRI (CMR) in analysing cardiac function and viability as well as predicting inducible and spontaneous ventricular tachyarrhythmia when performed early post MI. Following a MI patients are at high risk of sudden cardiac death (SCD). The risk is highest in the first 40 days; however, current guidelines exclude patients from receiving an ICD during this time. This limitation is based largely on a single study, The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT), which failed to demonstrate a benefit of early ICD implantation. However, this study was underpowered and used non-invasive tests to identify patients at high risk. EPS identifies patients with the substrate for re-entrant tachyarrhythmia, and has been found in multiple studies to predict patients at risk of SCD. Contrast-enhanced CMR is a non-invasive test without radiation exposure which can be used to assess left ventricular function. In addition, it provides information on myocardial viability, scar size and tissue heterogeneity. It has an emerging role as a predictor of mortality and spontaneous ventricular arrhythmia in patients with a previous MI. A total of 1,058 patients who are at high risk of SCD based on poor cardiac function (left ventricular ejection fraction (LVEF) ≤40%) following a ST-elevation or non-STE myocardial infarct will be enrolled in the trial. Patients will be randomised 1:1 to either the intervention or control arm. In the intervention arm all patients undergo early EPS. Patients with a positive study (inducible ventricular tachycardia cycle length ≥200ms) receive an ICD, while patients with a negative study (inducible ventricular fibrillation or no inducible VT) are discharged without an ICD, regardless of the LVEF. In the control arm patients are treated according to standard local practice. This involves early discharge and repeat assessment of cardiac function after 40 days or after 90 days following revascularisation (PCI or CABG). ICD implantation after 40 days according to current guidelines (LVEF≤30%, or ≤35% with New York Heart Association (NYHA) class II/III symptoms) could be considered, if part of local standard practice, however the ICD is not funded by the trial. A proportion of trial patients from both the intervention and control arms at \>48 hours following MI will undergo CMR to enable correlation with (1) inducible VT at EPS and (2) SCD and non-fatal arrhythmia on follow up. It will be used to simultaneously assess left ventricular function, ventricular strain, myocardial infarction size, and peri-infarction injury. The size of the infarct core, infarct gray zone (as a measure of tissue heterogeneity) and total infarct size will be quantified for each patient. All patients will be followed for 2 years with a combined primary endpoint of non-fatal arrhythmia and SCD. Non-fatal arrhythmia includes resuscitated cardiac arrest, sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) in participants without an ICD. Secondary endpoints will include all-cause mortality, non-sudden cardiovascular death, non-fatal repeat MI, heart failure and inappropriate ICD denial. Secondary endpoints for CMR correlation will include (1) the presence or absence of inducible VT at EP study, and (2) combined endpoint of appropriate ICD activation or SCD at follow up. It is anticipated that the intervention arm will reduce the primary endpoint as a result of prevention of a) early sudden cardiac deaths/cardiac arrest, and b) sudden cardiac death/cardiac arrest in patients with a LVEF of 31-40%. It is expected that the 2-year primary endpoint rate will be reduced from 6.7% in the control arm to 2.8% in the intervention arm with a relative risk reduction (RRR) of 68%. A two-group chi-squared test with a 0.05 two-sided significance level will have 80% power to detect the difference between a Group 1 proportion of 0.028 experiencing the primary endpoint and a Group 2 proportion of 0.067 experiencing the primary endpoint when the sample size in each group is 470. Assuming 1% crossover and 10% loss to follow up the required sample size is 1,058 (n=529 patients per arm). To test the hypothesis that tissue heterogeneity at CMR predicts both inducible and spontaneous ventricular tachyarrhythmias will require a sample size of 400 patients to undergo CMR. It is anticipated that the use of EPS will select a group of patients who will benefit from an ICD soon after a MI. This has the potential to change clinical guidelines and save a large number of lives.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Feb 2014
Longer than P75 for not_applicable
52 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 27, 2014
CompletedFirst Submitted
Initial submission to the registry
July 4, 2018
CompletedFirst Posted
Study publicly available on registry
July 17, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 6, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 6, 2029
May 7, 2024
May 1, 2024
13.8 years
July 4, 2018
May 6, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Sudden cardiac death
Cause of death will be determined based on information obtained from witnesses, family members, death certificates, hospital records and autopsy or coroner reports. Sudden cardiac death will be explicitly defined as death that occurs "suddenly and unexpectedly" in a patient in otherwise stable condition and includes witnessed instantaneous deaths (with or without documentation of arrhythmia), unwitnessed deaths if the patient had been seen within 24 hours before death (in the absence of another clear cause of death), deaths caused by incessant ventricular tachyarrhythmia, deaths considered a sequel of cardiac arrest and deaths resulting from pro-arrhythmia of anti-arrhythmic drugs.31 The remainder of deaths will be classified as either non-sudden cardiovascular death, or non-cardiovascular death. Operative deaths associated with the implantation of an ICD will be counted as non-sudden cardiovascular death.
2 years after randomisation
Non-fatal arrhythmia
Non-fatal arrhythmia includes resuscitated cardiac arrest, sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) in participants without an ICD. Resuscitated cardiac arrest is defined as a sudden circulatory arrest requiring cardiopulmonary resuscitation (CPR) (with or without documented arrhythmia) from which the patient regains consciousness. VT and VF are defined as ECG or telemetry-documented ventricular tachycardia or ventricular fibrillation. Only sustained ventricular tachycardia will be included (greater than 30 seconds of VT) or if the VT required emergency treatment with anti-arrhythmic medications or electrical cardioversion.
2 years after randomisation
Secondary Outcomes (8)
All-cause mortality
2 years after randomisation
Non-sudden cardiovascular death
2 years after randomisation
Non-fatal repeat MI
2 years after randomisation
Heart failure
2 years after randomisation
Inappropriate ICD denial
2 years after randomisation
- +3 more secondary outcomes
Study Arms (2)
Intervention Arm (Early EPS)
EXPERIMENTALThe intervention group all undergo electrophysiologic study early after myocardial infarction (within 40 days of MI). If the study is positive (inducible monomorphic ventricular tachycardia of cycle length greater than or equal to 200ms) participants have an ICD implanted. Participants with a negative study (no inducible arrhythmia or induced ventricular fibrillation/ ventricular flutter cycle length \<200ms) are discharged without an ICD. A proportion of trial patients from both the intervention and control arms at \>48 hours following revascularisation for STEMI will undergo CMR to enable correlation with (1) inducible VT at EPS and (2) SCD and non-fatal arrhythmia on follow up. CMR will simultaneously assess left ventricular function, ventricular strain, myocardial infarction size, and peri-infarction injury.
Control Arm (Standard Care)
ACTIVE COMPARATORThe control group receive ongoing standard care according to the practise of their institution. This includes discharge from hospital as per their treating physician and follow up as usual in the community. Participants in this group would be eligible to receive an ICD according to the standard practise of their cardiologist (guideline recommendations are after 40 days following myocardial infarction or 90 days following revascularisation only in patients with left ventricular ejection fraction less than or equal to 30% or less than or equal to 35% in the presence of heart failure). A proportion of trial patients from both the intervention and control arms at \>48 hours following revascularisation for STEMI will undergo CMR to enable correlation with (1) inducible VT at EPS and (2) SCD and non-fatal arrhythmia on follow up. CMR will simultaneously assess left ventricular function, ventricular strain, myocardial infarction size, and peri-infarction injury.
Interventions
EPS will be performed in all patients in the intervention arm with programmed ventricular stimulation with a drive train of 8 beats at 400 ms with up to 4 extrastimuli and stimulation from the right ventricular apex with current delivered at twice pacing threshold. The end point for stimulation will be sustained monomorphic ventricular tachycardia (VT) lasting \> 10 seconds. If sustained monomorphic VT with cycle length (CL) ≥200ms is induced by ≤4 extra stimuli the EPS result will be considered positive for inducible VT.30 Ventricular fibrillation or flutter with CL\<200ms will be considered a negative result. The Programmed Ventricular Stimulation (PVS) induction will be repeated a second time if the initial induction was negative for VT.
The control group receive ongoing standard care according to the practise of their institution. This includes discharge from hospital as per their treating physician and follow up as usual in the community. Participants in this group would be eligible to receive an ICD according to the standard practise of their cardiologist (guideline recommendations are after 40 days following myocardial infarction or 90 days following revascularisation only in patients with left ventricular ejection fraction less than or equal to 30% or less than or equal to 35% in the presence of heart failure).
CMR will be performed on either a 1.5-T or 3-T scanner. Gadolinium contrast (Gd-BOPTA, MultihanceTM) will be administered for quantification myocardial perfusion imaging with subsequent late gadolinium enhanced imaging after a total dose of 0.1mmol/kg. Exclusion criteria specific for CMR will include pregnancy, renal insufficiency defined as glomerular filtration rate (GFR) \<30 mL/min, contraindication to MRI (including non-MRI compatible pacemaker/ICD or metal implants, non-MR safe prosthetic heart valves), claustrophobia which cannot be controlled via standard methods (benzodiazepines and/or sedative antihistamine administration) and prior allergic reaction to gadolinium-based contrast agent.
Eligibility Criteria
You may qualify if:
- days (inclusive) following a myocardial infarct
- Impaired left ventricular systolic function (LVEF≤40% or at least moderately impaired)
You may not qualify if:
- Age \<18 or \>85;
- Pregnancy;
- Nursing home resident dependent on one or more activities of daily living;
- Significant non-cardiac co-morbidity with high likelihood of death within 1 year (this would include any metastatic malignancy, or other terminal disease);
- Significant psychiatric illnesses that may be aggravated by device implantation or that may preclude regular follow up;
- Intravenous drug abuse (ongoing);
- Unresolved infection associated with risk for hematogenous seeding;
- Pre-existing implantable cardioverter-defibrillator (ICD);
- Secondary prevention indication for an ICD (i.e. sustained ventricular arrhythmias occurring more than 48 hours after qualifying myocardial infarction (patients with ventricular arrhythmias occurring ≤48 hours of myocardial infarction, or with non-sustained ventricular tachycardia at any time, are not excluded));
- On the heart transplant list;
- Recurrent unstable angina despite revascularisation (defined as ongoing chest pain or ischemic symptoms at rest or with minimal exertion despite adequate treatment with anti-anginal medications);\*\*
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (52)
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Canberra Hospital
Garran, Australian Capital Territory, 2605, Australia
Nepean Hospital
Kingswood, New South Wales, 2747, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, 2305, Australia
Prince of Wales Hospital
Randwick, New South Wales, 2031, Australia
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Wollongong Hospital
Wollongong, New South Wales, 2500, Australia
Sunshine Coast University Hospital
Birtinya, Queensland, 4575, Australia
Carins Hospital
Cairns, Queensland, 4870, Australia
The Prince Charles Hospital
Chermside, Queensland, 4032, Australia
The Townsville Hospital
Douglas, Queensland, 4814, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Gold Coast University Hospital
Southport, Queensland, 4215, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112, Australia
MonashHeart
Clayton, Victoria, 3168, Australia
Northern Hospital
Epping, Victoria, 3076, Australia
Austin Hospital
Melbourne, Victoria, 3084, Australia
Western Health, Sunshine and Footscray Hospitals
Melbourne, Victoria, Australia
Institute for Clinical and Experimental Medicine
Prague, Czechia
Cardiovascular Center Bad Neustadt
Bad Neustadt an der Saale, Germany
Klinikum Brandenburg
Brandenburg, Germany
Universitaetsmedizin Gittingen (University of Göttingen Medical Center)
Göttingen, Germany
Leipzig Heart Center
Leipzig, Germany
Universitätsklinikum Leipzig
Leipzig, Germany
General Hospital of Athens Giorgios Gennimatas
Athens, Greece
General Hospital of Athens Ippokrateio
Athens, Greece
University Hospital of Heraklion Crete
Heraklion, Greece
Semmelweis University Heart and Vascular Center
Budapest, Hungary
University of Debrecen
Debrecen, Hungary
University of Pécs
Pécs, Hungary
Sharee Zadek Medical Centre
Jerusalem, Israel
Paul Stradins University Clinic
Riga, Latvia
Institut Jantung Negara Sdn Bhd
Kuala Lumpur, 50400, Malaysia
Pusat Jantung Sarawak (PJS)(Sarawak Heart Centre)
Kuala Lumpur, Malaysia
Auckland City Hospital
Grafton, Auckland, 1023, New Zealand
Middlemore Hospital
Otahuhu, Auckland, 2025, New Zealand
Waikato Hospital
Hamilton W., Hamilton, 3204, New Zealand
Christchurch Hospital
Christchurch, New Zealand
Wellington Hospital
Wellington, 2820, New Zealand
Medical University of Łódź - Biegański Provincial Specialist Hospital
Lodz, Poland
Medical University of Łódź - WAM Hospital
Lodz, Poland
Medical University of Łódź
Lodz, Poland
National Institute of Cardiology Warsaw
Warsaw, Poland
Almazov National Medical Research Centre
Saint Petersburg, Russia
Samara State Medical University
Samara, Russia
National University Heart Centre, Singapore (NUHCS)
Singapore, 119074, Singapore
The National Institute of Cardiovascular Diseases
Bratislava, Slovakia
University Hospital Basel
Basel, 4031, Switzerland
University Hospital Bern
Bern, 3010, Switzerland
Lausanne University Hospital
Lausanne, Switzerland
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Study Principal Investigator Study Principal Investigator
Western Sydney Local Health District
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Senior Staff Specialist Cardiologist
Study Record Dates
First Submitted
July 4, 2018
First Posted
July 17, 2018
Study Start
February 27, 2014
Primary Completion (Estimated)
December 6, 2027
Study Completion (Estimated)
December 6, 2029
Last Updated
May 7, 2024
Record last verified: 2024-05