Early ICD Implantation for Heart Attack

(PROTECT-ICD Trial)

Recruiting at 46 trial locations

Overseen By Anjalee T Amarasekera

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Western Sydney Local Health District

Disqualifiers: Age <18 or >85, Pregnancy, Terminal disease, Psychiatric illnesses, Intravenous drug abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

1058 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment involving early ICD implantation and electrophysiology study (EPS) for heart attack patients?

Research shows that using an electrophysiology study (EPS) to guide the implantation of an implantable cardioverter defibrillator (ICD) can be beneficial for patients at high risk of sudden death after a heart attack, especially when combined with optimal beta-blocker treatment. ^{1 2 3 4 5}

Is early ICD implantation safe for heart attack patients?

Electrophysiologic studies (EPS) and implantable cardioverter-defibrillators (ICDs) are generally safe for most patients, and they are often used together to help prevent sudden death in high-risk heart attack patients. ^{1 2 3 4 5}

How does the electrophysiology study (EPS) treatment differ from other treatments for heart attack?

The electrophysiology study (EPS) treatment is unique because it involves testing the heart's electrical system to identify and manage abnormal heart rhythms, which can help determine if an implantable cardioverter defibrillator (ICD) is needed. This approach is particularly useful for patients at high risk of sudden death after a heart attack, as it can guide the decision to implant an ICD early, potentially improving outcomes compared to waiting until later. ^{1 3 4 5 6}

Research Team

Study Principal Investigator Study Principal Investigator

Principal Investigator

Western Sydney Local Health District

Eligibility Criteria

This trial is for adults aged 18-85 who've had a heart attack within the last 2-40 days and have reduced heart function (LVEF≤40%). It's not for pregnant women, nursing home residents dependent on care, those with terminal illnesses or drug abuse issues, unresolved infections, existing ICDs, unstable angina despite treatment, severe psychiatric illness, listed for heart transplant or severe untreatable shortness of breath.

Inclusion Criteria

My heart's pumping ability is reduced.

I had a heart attack between 2 and 40 days ago.

Exclusion Criteria

I have severe heart failure that doesn't improve with treatment.

You have a device called an implantable cardioverter-defibrillator (ICD) already in your body.

I need an ICD because of serious heart rhythm problems after a heart attack.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intervention

Participants in the intervention arm undergo early electrophysiology study (EPS) within 40 days of myocardial infarction. Based on EPS results, ICD implantation is decided.

40 days

Control

Participants in the control arm receive standard care, including discharge and follow-up assessment of cardiac function after 40 or 90 days.

90 days

Follow-up

Participants are monitored for safety and effectiveness, including endpoints like non-fatal arrhythmia and sudden cardiac death.

2 years

Treatment Details

Interventions

• Cardiac Magnetic Resonance (CMR)
• Electrophysiology study (EPS)
• Standard Care

Trial Overview The PROTECT-ICD trial is testing whether an early electrophysiology study (EPS) can help decide if patients need an implantable cardioverter-defibrillator (ICD) after a heart attack to prevent sudden cardiac death. Some patients will also get a cardiac MRI to assess their risk. The goal is to see if this approach saves more lives compared to standard care.

Participant Groups

Group I: Intervention Arm (Early EPS) Experimental Treatment 2 Interventions

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.

Group II: Control Arm (Standard Care) Active Control 2 Interventions

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.

Electrophysiology study (EPS) is already approved in European Union, United States for the following indications:

Approved in European Union as Electrophysiology study for:

• Guiding ICD implantation in patients with poor cardiac function following myocardial infarction

Approved in United States as Electrophysiology study for:

• Guiding ICD implantation in patients with poor cardiac function following myocardial infarction

Who Is Running the Clinical Trial?

Western Sydney Local Health District

Lead Sponsor

Trials

42

Recruited

18,600+

Findings from Research

In a study of 143 patients who survived a recent heart attack and were at high risk for sudden death, the use of an electrophysiological study (EPS)-guided strategy for implantable cardioverter defibrillator (ICD) implantation showed a trend towards lower mortality compared to conventional therapy, but the difference was not statistically significant.

Despite optimal treatment, the overall mortality rate remained high in this population, with 19% of patients dying during a follow-up period of about 18 months, indicating that further research is needed to establish the effectiveness of EPS-guided strategies in improving survival after a heart attack.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial. Raviele, A., Bongiorni, MG., Brignole, M., et al.[2022]

Electrophysiology studies (EPS) were conducted in 33,786 out of 275,273 patients undergoing ICD implantation, primarily in those with less clear risk factors for sudden death, indicating a targeted approach to risk stratification.

Induced ventricular arrhythmias were common in both primary (46.1%) and secondary (54.2%) prevention ICD recipients, but complication rates from EPS were not higher, suggesting that EPS can be safely used to identify patients at greater risk for future arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrophysiology studies in patients undergoing ICD implantation: findings from the NCDR®. Cheng, A., Wang, Y., Berger, RD., et al.[2012]

A study involving 160 patients showed that performing electrophysiologic study (EPS) and transvenous ICD placement in the same setting is as safe as doing them separately, with similar complication rates (5.0% for same-setting vs. 4.9% for separate-setting).

The same-setting procedure not only maintains safety but also significantly reduces costs, with an average savings of $2,121 per patient compared to separate procedures, making it a more efficient option for ICD therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and potential cost savings of same-setting electrophysiologic testing and placement of transvenous implantable cardioverter-defibrillators. Pires, LA., Ravi, S., Lal, VR., et al.[2020]

In a study of 55 patients with implantable cardioverter/defibrillators (ICDs), sustained monomorphic ventricular tachycardia (VT) was induced in 72% of follow-up noninvasive electrophysiological studies (EPSs) after initial induction, indicating ongoing risk for arrhythmias over time.

Patients who consistently showed noninducibility of VT during follow-up had a significantly lower chance (11%) of experiencing spontaneous VT, suggesting that the underlying conditions for arrhythmias may change and improve over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term reproducibility of ventricular tachycardia induction in patients with implantable cardioverter/defibrillators. Serial noninvasive studies. Gillis, AM., Sheldon, RS., Wyse, DG., et al.[2022]

Electrophysiological studies (EPS) and programmed ventricular stimulation (PVS) are crucial before implanting a cardioverter defibrillator (ICD) in patients with cardiac arrest but no structural heart disease, as they can identify treatable causes and potentially avoid unnecessary ICD implantation.

In cases of unclear wide-complex tachycardias or syncope with nonsustained VTs in patients with structural heart disease, EPS and PVS can help assess risk, but they are less useful for patients with impaired left ventricular function who are already candidates for ICD implantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is an electrophysiological study always necessary before defibrillator implantation?]. Bänsch, D., Antz, M.[2015]

In a study of 204 sudden cardiac arrest survivors, those treated with an implantable cardioverter/defibrillator (ICD) had a significantly lower overall mortality rate (14.6%) compared to those receiving electrophysiologically guided antiarrhythmic drug therapy (43.2%).

The ICD group also experienced much lower rates of cardiac (12% vs. 43%) and arrhythmogenic mortality (1% vs. 16%), indicating that ICDs are a more effective option for preventing sudden cardiac death in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of sudden cardiac arrest survivors and electrophysiologically guided antiarrhythmic therapy. Hennersdorf, MG., Niebch, V., Vester, EG., et al.[2017]

References

1. England pubmed.ncbi.nlm.nih.gov

Early EPS/ICD strategy in survivors of acute myocardial infarction with severe left ventricular dysfunction on optimal beta-blocker treatment. The BEta-blocker STrategy plus ICD trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Electrophysiology studies in patients undergoing ICD implantation: findings from the NCDR®. [2012]

3. United States pubmed.ncbi.nlm.nih.gov

Safety and potential cost savings of same-setting electrophysiologic testing and placement of transvenous implantable cardioverter-defibrillators. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Long-term reproducibility of ventricular tachycardia induction in patients with implantable cardioverter/defibrillators. Serial noninvasive studies. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

[Is an electrophysiological study always necessary before defibrillator implantation?]. [2015]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Long-term follow-up of sudden cardiac arrest survivors and electrophysiologically guided antiarrhythmic therapy. [2017]