Programmed Ventricular Stimulation to Risk Stratify for Early Cardioverter-Defibrillator (ICD) Implantation to Prevent Tachyarrhythmias Following Acute Myocardial Infarction (PROTECT-ICD)

Status: Recruiting
Location: See all (51) locations...
Intervention Type: Other, Procedure
Study Type: Interventional
Study Phase: Not Applicable
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 85
Healthy Volunteers: f
View:

• 2-40 days (inclusive) following a myocardial infarct

• Impaired left ventricular systolic function (LVEF≤40% or at least moderately impaired)

Locations
United States
Massachusetts
Beth Israel Deaconess Medical Center
NOT_YET_RECRUITING
Boston
Other Locations
Australia
Sunshine Coast University Hospital
RECRUITING
Birtinya
Carins Hospital
RECRUITING
Cairns
The Prince Charles Hospital
RECRUITING
Chermside
MonashHeart
COMPLETED
Clayton
The Townsville Hospital
RECRUITING
Douglas
Lyell McEwin Hospital
RECRUITING
Elizabeth Vale
Northern Hospital
WITHDRAWN
Epping
Canberra Hospital
RECRUITING
Garran
Royal Brisbane and Women's Hospital
RECRUITING
Herston
Nepean Hospital
RECRUITING
Kingswood
Austin Hospital
TERMINATED
Melbourne
Western Health, Sunshine and Footscray Hospitals
WITHDRAWN
Melbourne
John Hunter Hospital
RECRUITING
New Lambton Heights
Prince of Wales Hospital
RECRUITING
Randwick
Royal North Shore Hospital
RECRUITING
Saint Leonards
Gold Coast University Hospital
RECRUITING
Southport
Westmead Hospital
RECRUITING
Westmead
Wollongong Hospital
RECRUITING
Wollongong
Princess Alexandra Hospital
RECRUITING
Woolloongabba
Germany
Cardiovascular Center Bad Neustadt
RECRUITING
Bad Neustadt An Der Saale
Klinikum Brandenburg
RECRUITING
Brandenburg
Universitaetsmedizin Gittingen (University of Göttingen Medical Center)
ACTIVE_NOT_RECRUITING
Göttingen
Leipzig Heart Center
ACTIVE_NOT_RECRUITING
Leipzig
Universitätsklinikum Leipzig
NOT_YET_RECRUITING
Leipzig
Greece
General Hospital of Athens Giorgios Gennimatas
ACTIVE_NOT_RECRUITING
Athens
General Hospital of Athens Ippokrateio
ACTIVE_NOT_RECRUITING
Athens
University Hospital of Heraklion Crete
NOT_YET_RECRUITING
Heraklion
Hungary
Semmelweis University Heart and Vascular Center
RECRUITING
Budapest
University of Debrecen
RECRUITING
Debrecen
University of Pécs
RECRUITING
Pécs
Israel
Sharee Zadek Medical Centre
RECRUITING
Jerusalem
Latvia
Paul Stradins University Clinic
RECRUITING
Riga
Malaysia
Institut Jantung Negara Sdn Bhd
RECRUITING
Kuala Lumpur
Pusat Jantung Sarawak (PJS)(Sarawak Heart Centre)
RECRUITING
Kuala Lumpur
New Zealand
Christchurch Hospital
RECRUITING
Christchurch
Auckland City Hospital
WITHDRAWN
Grafton
Waikato Hospital
RECRUITING
Hamilton W.
Middlemore Hospital
WITHDRAWN
Otahuhu
Wellington Hospital
RECRUITING
Wellington
Poland
Medical University of Łódź
RECRUITING
Lodz
Medical University of Łódź - Biegański Provincial Specialist Hospital
RECRUITING
Lodz
Medical University of Łódź - WAM Hospital
RECRUITING
Lodz
National Institute of Cardiology Warsaw
NOT_YET_RECRUITING
Warsaw
Russian Federation
Almazov National Medical Research Centre
NOT_YET_RECRUITING
Saint Petersburg
Samara State Medical University
WITHDRAWN
Samara
Singapore
National University Heart Centre, Singapore (NUHCS)
RECRUITING
Singapore
Slovakia
The National Institute of Cardiovascular Diseases
NOT_YET_RECRUITING
Bratislava
Switzerland
University Hospital Basel
RECRUITING
Basel
University Hospital Bern
RECRUITING
Bern
Lausanne University Hospital
WITHDRAWN
Lausanne
Contact Information
Primary
Pramesh Kovoor
pramesh.kovoor@sydney.edu.au
+61 2 8890 6030
Backup
Anjalee T Amarasekera
Anjalee.Amarasekera@health.nsw.gov.au
+61 2 8890 4719
Time Frame
Start Date: 2014-02-27
Estimated Completion Date: 2029-12-06
Participants
Target number of participants: 1058
Treatments
Experimental: 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.
Active_comparator: 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.
Sponsors
Leads: Western Sydney Local Health District

This content was sourced from clinicaltrials.gov