Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias Following Acute Myocardial Infarction (PROTECT-ICD)
NCT ID: NCT03588286
Last Updated: 2024-05-07
Study Results
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Basic Information
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RECRUITING
NA
1058 participants
INTERVENTIONAL
2014-02-27
2029-12-06
Brief Summary
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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.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
DOUBLE
Study Groups
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Intervention Arm (Early EPS)
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.
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.
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.
Control Arm (Standard Care)
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.
Standard Care
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)
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.
Interventions
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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.
Standard Care
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)
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
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Inclusion Criteria
* Impaired left ventricular systolic function (LVEF≤40% or at least moderately impaired)
Exclusion Criteria
2. Pregnancy;
3. Nursing home resident dependent on one or more activities of daily living;
4. Significant non-cardiac co-morbidity with high likelihood of death within 1 year (this would include any metastatic malignancy, or other terminal disease);
5. Significant psychiatric illnesses that may be aggravated by device implantation or that may preclude regular follow up;
6. Intravenous drug abuse (ongoing);
7. Unresolved infection associated with risk for hematogenous seeding;
8. Pre-existing implantable cardioverter-defibrillator (ICD);
9. 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));
10. On the heart transplant list;
11. 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);\*\*
12. 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.
18 Years
85 Years
ALL
No
Sponsors
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Western Sydney Local Health District
OTHER
Responsible Party
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Pramesh Kovoor
Senior Staff Specialist Cardiologist
Principal Investigators
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Study Principal Investigator Study Principal Investigator
Role: PRINCIPAL_INVESTIGATOR
Western Sydney Local Health District
Locations
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Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States
Canberra Hospital
Garran, Australian Capital Territory, Australia
Nepean Hospital
Kingswood, New South Wales, Australia
John Hunter Hospital
New Lambton Heights, New South Wales, Australia
Prince of Wales Hospital
Randwick, New South Wales, Australia
Royal North Shore Hospital
Saint Leonards, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Wollongong Hospital
Wollongong, New South Wales, Australia
Sunshine Coast University Hospital
Birtinya, Queensland, Australia
Carins Hospital
Cairns, Queensland, Australia
The Prince Charles Hospital
Chermside, Queensland, Australia
The Townsville Hospital
Douglas, Queensland, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Gold Coast University Hospital
Southport, Queensland, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Lyell McEwin Hospital
Elizabeth Vale, South Australia, Australia
MonashHeart
Clayton, Victoria, Australia
Northern Hospital
Epping, Victoria, Australia
Austin Hospital
Melbourne, Victoria, 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, , Malaysia
Pusat Jantung Sarawak (PJS)(Sarawak Heart Centre)
Kuala Lumpur, , Malaysia
Auckland City Hospital
Grafton, Auckland, New Zealand
Middlemore Hospital
Otahuhu, Auckland, New Zealand
Waikato Hospital
Hamilton W., Hamilton, New Zealand
Christchurch Hospital
Christchurch, , New Zealand
Wellington Hospital
Wellington, , 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, , Singapore
The National Institute of Cardiovascular Diseases
Bratislava, , Slovakia
University Hospital Basel
Basel, , Switzerland
University Hospital Bern
Bern, , Switzerland
Lausanne University Hospital
Lausanne, , Switzerland
Countries
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Central Contacts
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Other Identifiers
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ACTRN12614000042640
Identifier Type: REGISTRY
Identifier Source: secondary_id
PROTECT-ICD, Version 5
Identifier Type: -
Identifier Source: org_study_id
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