Sudden Cardiac DeathPROTECT-ICDNCT03588286
Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias Following Acute Myocardial Infarction (PROTECT-ICD)
A study testing Electrophysiology study (EPS) and Cardiac Magnetic Resonance (CMR) in people with Sudden Cardiac Death, run by Western Sydney Local Health District at 52 sites in 15 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Sudden Cardiac Death
- What is being tested?
- Electrophysiology study (EPS) and Cardiac Magnetic Resonance (CMR)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,058 participants
- Where
- 52 sitesin 15 countries
- Study dates
- 27 Feb 2014to 6 Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 2-40 days (inclusive) following a myocardial infarct
- Impaired left ventricular systolic function (LVEF≤40% or at least moderately impaired)
Who cannot join
- 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);
Show all 12Show fewer
- 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);**
- Congestive heart failure New York Heart Association class IV, defined as shortness of breath at rest, which is refractory to medical treatment (not responding to treatment) NOTE: patients who meet exclusion based on (11) or (12) can be reviewed again in 2-3 days and if symptoms have resolved or treatment performed can be re-considered for inclusion.
Trial locations and contacts
52 sites in 15 countries. Contact the study team or a site near you to ask about taking part.
52 sites in 15 countries
Australia19 sites, 15 recruiting
- Recruiting
Sunshine Coast University Hospital
Birtinya, Queensland, 4575
- Recruiting
Carins Hospital
Cairns, Queensland, 4870
- Recruiting
The Prince Charles Hospital
Chermside, Queensland, 4032
- Completed
MonashHeart
Clayton, Victoria, 3168
- Recruiting
The Townsville Hospital
Douglas, Queensland, 4814
- Recruiting
Lyell McEwin Hospital
Elizabeth Vale, South Australia, 5112
- Withdrawn
Northern Hospital
Epping, Victoria, 3076
- Recruiting
Canberra Hospital
Garran, Australian Capital Territory, 2605
- Recruiting
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029
- Recruiting
Nepean Hospital
Kingswood, New South Wales, 2747
- Terminated
Austin Hospital
Melbourne, Victoria, 3084
- Withdrawn
Western Health, Sunshine and Footscray Hospitals
Melbourne, Victoria
- Recruiting
John Hunter Hospital
New Lambton Heights, New South Wales, 2305
- Recruiting
Prince of Wales Hospital
Randwick, New South Wales, 2031
- Recruiting
Royal North Shore Hospital
Saint Leonards, New South Wales, 2065
- Recruiting
Gold Coast University Hospital
Southport, Queensland, 4215
- Recruiting
Westmead Hospital
Westmead, New South Wales, 2145
- Recruiting
Wollongong Hospital
Wollongong, New South Wales, 2500
- Recruiting
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
Germany5 sites, 3 recruiting
- Recruiting
Cardiovascular Center Bad Neustadt
Bad Neustadt an der Saale
- Recruiting
Klinikum Brandenburg
Brandenburg
- Active, not recruiting
Universitaetsmedizin Gittingen (University of Göttingen Medical Center)
Göttingen
- Active, not recruiting
Leipzig Heart Center
Leipzig
- Not yet recruiting
Universitätsklinikum Leipzig
Leipzig
New Zealand5 sites, 3 recruiting
- Recruiting
Christchurch Hospital
Christchurch
- Withdrawn
Auckland City Hospital
Grafton, Auckland, 1023
- Recruiting
Waikato Hospital
Hamilton W., Hamilton, 3204
- Withdrawn
Middlemore Hospital
Otahuhu, Auckland, 2025
- Recruiting
Wellington Hospital
Wellington, 2820
Poland4 sites, 4 recruiting
- Recruiting
Medical University of Łódź - Biegański Provincial Specialist Hospital
Lodz
- Recruiting
Medical University of Łódź - WAM Hospital
Lodz
- Recruiting
Medical University of Łódź
Lodz
- Not yet recruiting
National Institute of Cardiology Warsaw
Warsaw
Greece3 sites, 1 recruiting
- Active, not recruiting
General Hospital of Athens Giorgios Gennimatas
Athens
- Active, not recruiting
General Hospital of Athens Ippokrateio
Athens
- Not yet recruiting
University Hospital of Heraklion Crete
Heraklion
Hungary3 sites, 3 recruiting
- Recruiting
Semmelweis University Heart and Vascular Center
Budapest
- Recruiting
University of Debrecen
Debrecen
- Recruiting
University of Pécs
Pécs
Switzerland3 sites, 2 recruiting
- Recruiting
University Hospital Basel
Basel, 4031
- Recruiting
University Hospital Bern
Bern, 3010
- Withdrawn
Lausanne University Hospital
Lausanne
Malaysia2 sites, 2 recruiting
- Recruiting
Institut Jantung Negara Sdn Bhd
Kuala Lumpur, 50400
- Recruiting
Pusat Jantung Sarawak (PJS)(Sarawak Heart Centre)
Kuala Lumpur
Russia2 sites, 1 recruiting
- Not yet recruiting
Almazov National Medical Research Centre
Saint Petersburg
- Withdrawn
Samara State Medical University
Samara
United States1 site, 1 recruiting
- Not yet recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Czechia1 site, 1 recruiting
- Not yet recruiting
Institute for Clinical and Experimental Medicine
Prague
Singapore1 site, 1 recruiting
- Recruiting
National University Heart Centre, Singapore (NUHCS)
Singapore, 119074
Slovakia1 site, 1 recruiting
- Not yet recruiting
The National Institute of Cardiovascular Diseases
Bratislava
About this study
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.
Read more
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.
- Conditions
- Sudden Cardiac Death
- Being tested
- Electrophysiology study (EPS), Standard Care, Cardiac Magnetic Resonance (CMR)
- Keywords
- Myocardial Infarction (MI), Sudden Cardiac Death (SCD), Electrophysiological Study (EPS), Ventricular Tachycardia (VT)
- Medical subject headings
- Death, Sudden, Cardiac, Myocardial Infarction, Tachycardia, Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrophysiology study (EPS)Procedure or surgery
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.
Standard CareOther
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).
Cardiac Magnetic Resonance (CMR)Procedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Arm (Early EPS) | Experimental | The 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. Receives: Procedure: Electrophysiology study (EPS); Procedure: Cardiac Magnetic Resonance (CMR) |
| Control Arm (Standard Care) | Active comparator | 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).
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. Receives: Other: Standard Care; Procedure: Cardiac Magnetic Resonance (CMR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 years after randomisation
Secondary outcomes (8)
All-cause mortality
All deaths.
Measured: 2 years after randomisation
Non-sudden cardiovascular death
Non-sudden cardiovascular deaths will be classified as death due to myocardial infarction, heart failure or another cardiovascular cause including cerebrovascular or peripheral vascular causes.
Measured: 2 years after randomisation
Non-fatal repeat MI
Non-fatal repeat MI requires the presence of two of the following three: symptoms of myocardial ischaemia, a characteristic rise and fall in cardiac markers and a typical ECG pattern involving the development of Q waves or persistent T wave changes.
Measured: 2 years after randomisation
Heart failure
Heart failure is defined as symptoms or signs consistent with congestive heart failure with use of intravenous decongestive therapy greater than 2 hours (IV diuretics, IV nesiritide, IV inotropes) in a patient not requiring hospital admission, or, augmented heart failure regimen with oral or intravenous medications in patients requiring hospital admission.
Measured: 2 years after randomisation
Inappropriate ICD denial
Inappropriate ICD denial will be defined as patients who did not receive an ICD based on their intervention allocation, who went on to have documented non-fatal arrhythmia or sudden cardiac death.
Measured: 2 years after randomisation
Appropriate ICD activations (in patients with ICD)
Appropriate ICD activation will be defined as ventricular tachyarrhythmia due to VT which meets the treatment criteria defined above or VF.
Measured: 2 years after randomisation
Inappropriate ICD activations (in patients with ICD)
Inappropriate ICD activations will include supra-ventricular tachycardia, atrial fibrillation/flutter, T wave over-sensing, sinus tachycardia and noise from lead complications or extraneous noise.
Measured: 2 years after randomisation
Complications or re-hospitalisation associated with ICD implantation (in patients with ICD)
Complications or re-hospitalisation associated with ICD implantation (in patients with ICD)
Measured: 2 years after randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2018
- Study start27 Feb 2014
- Primary completion6 Dec 2027 (estimated)
- Study completion6 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sudden Cardiac DeathStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 1,058 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Western Sydney Local Health District
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pramesh Kovoor, Western Sydney Local Health District
- Investigators
- Study Principal Investigator Study Principal Investigator, Principal investigator, Western Sydney Local Health District
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03588286
- Sponsor's protocol ID
- PROTECT-ICD, Version 5
- Other IDs
- ACTRN12614000042640
- Acronym
- PROTECT-ICD
- Status last verified
- May 2024
- First submitted
- 4 Jul 2018
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias Following Acute Myocardial Infarction (PROTECT-ICD)
- ClinicalTrials.gov ID
- NCT03588286
- Acronym / sponsor ID
- PROTECT-ICD / PROTECT-ICD, Version 5
- Conditions
- Sudden Cardiac Death
- Keywords
- Myocardial Infarction (MI), Sudden Cardiac Death (SCD), Electrophysiological Study (EPS), Ventricular Tachycardia (VT)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 1,058 participants (estimated)
- Lead sponsor
- Western Sydney Local Health DistrictUniversity, hospital or other
- Study start
- 27 Feb 2014 (actual)
- Primary completion
- 6 Dec 2027 (estimated)
- Study completion
- 6 Dec 2029 (estimated)
- First posted
- 17 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention Arm (Early EPS) | Experimental | Procedure: Electrophysiology study (EPS), Procedure: Cardiac Magnetic Resonance (CMR)The 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 comparator | Other: Standard Care, Procedure: Cardiac Magnetic Resonance (CMR)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). 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. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 2-40 days (inclusive) following a myocardial infarct
- Impaired left ventricular systolic function (LVEF≤40% or at least moderately impaired)
Key exclusion criteria (12 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Electrophysiology study (EPS)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. | Procedure or surgery | Intervention Arm (Early EPS) |
| Standard CareThe 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). | Other | Control Arm (Standard Care) |
| Cardiac Magnetic Resonance (CMR)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. | Procedure or surgery | Control Arm (Standard Care), Intervention Arm (Early EPS) |
Primary outcome
Sudden cardiac death
Time frame: 2 years after randomisation
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.
Non-fatal arrhythmia
Time frame: 2 years after randomisation
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.
8 secondary outcomes
All-cause mortality
Time frame: 2 years after randomisation
Non-sudden cardiovascular death
Time frame: 2 years after randomisation
Non-fatal repeat MI
Time frame: 2 years after randomisation
Heart failure
Time frame: 2 years after randomisation
Inappropriate ICD denial
Time frame: 2 years after randomisation
Appropriate ICD activations (in patients with ICD)
Time frame: 2 years after randomisation
Inappropriate ICD activations (in patients with ICD)
Time frame: 2 years after randomisation
Complications or re-hospitalisation associated with ICD implantation (in patients with ICD)
Time frame: 2 years after randomisation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Study Principal Investigator Study Principal Investigator principal investigator
Western Sydney Local Health District
52 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Electrophysiology study (EPS) and Cardiac Magnetic Resonance (CMR) in people with Sudden Cardiac Death, run by Western Sydney Local Health District at 52 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 52 sites in Australia, Germany, New Zealand, Poland, Greece and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Pramesh Kovoor (+61 2 8890 6030, pramesh.kovoor@sydney.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sudden cardiac death (time frame: 2 years after randomisation). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.