Early ICD Implantation for Heart Attack

(PROTECT-ICD Trial)

Recruiting at 53 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to prevent sudden cardiac death in individuals who have experienced a heart attack and have weak heart function. Participants will be randomly assigned to either undergo an early electrophysiology study (EPS) to determine the need for an implantable cardioverter-defibrillator (ICD) or follow standard care practices. Cardiac MRI will assess heart health and predict heart rhythm problems. This trial suits those who have had a heart attack within the last 40 days and have poor heart pumping ability (left ventricular ejection fraction of 40% or less). As an unphased trial, it offers participants the chance to contribute to important research that could enhance future heart attack care.

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 prior data suggests that this trial's methods are safe for patients with poor cardiac function following a myocardial infarct?

Research has shown that electrophysiology studies (EPS) can identify patients at higher risk of sudden cardiac death after a heart attack. One study found that patients with a negative EPS result (indicating no dangerous heart rhythms during the test) had a much lower risk of major heart problems compared to those with a positive result. Specifically, only 4.3% of the negative group experienced serious issues, while 22% of the positive group did. This suggests that EPS can effectively identify those who might benefit from an implantable cardioverter-defibrillator (ICD) early on.

However, earlier research, such as the DINAMIT trial, did not demonstrate clear survival benefits from early ICD implantation after a heart attack. This highlights the ongoing debate about the optimal timing for ICD implantation. Despite this, some studies have shown good results within three months of a heart event for certain high-risk patients.

Overall, while EPS shows promise in identifying at-risk patients, the best timing for ICD use remains under study. The safety and benefits may vary depending on individual circumstances and timing after the heart attack. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the early use of electrophysiology studies (EPS) after a heart attack because it offers a proactive approach to identifying patients at risk of dangerous heart rhythms. Unlike the standard of care, which typically involves waiting at least 40 days post-heart attack before considering an ICD (implantable cardioverter-defibrillator) based on specific risk criteria, this method employs EPS to potentially detect risk much earlier. If the EPS results show a risk of serious arrhythmias, an ICD can be implanted promptly, possibly improving outcomes by preventing sudden cardiac events sooner. This early intervention strategy could significantly change how we manage patients after a heart attack, potentially offering a more tailored and timely protection against life-threatening arrhythmias.

What evidence suggests that this trial's treatments could be effective for preventing sudden cardiac death after a heart attack?

Research shows that an electrophysiology study (EPS), a special heart test, can help doctors determine if a patient needs a defibrillator soon after a heart attack. This trial includes an intervention arm where participants undergo EPS early after myocardial infarction. A positive EPS, indicating ventricular tachycardia, leads to the implantation of an implantable cardioverter-defibrillator (ICD). Past studies have shown that patients with weak heart function who received an ICD based on EPS results had better survival rates. For instance, one study found that patients who received an ICD early had lower death rates. Another study showed that after one year, 14% of patients in the EPS-guided group had died, compared to 18% in the group that received standard care. These findings suggest that EPS can help identify patients who might benefit from an ICD soon after a heart attack. ^{1 6 7 8 9}

Who Is on the Research Team?

Study Principal Investigator Study Principal Investigator

Principal Investigator

Western Sydney Local Health District

Are You a Good Fit for This Trial?

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.

You are waiting for a heart transplant.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20650333/

Electrophysiology-guided defibrillator implantation early ... Results: Defibrillator was implanted in 71% of EP(pos) patients (median 21 days post-MI) and withheld in 94% of EP(neg) patients. At 2 years, primary endpoint ...

2. ahajournals.org ahajournals.org/doi/10.1161/circulationaha.108.836791

Outcomes of Early Risk Stratification and Targeted ... Early ICD implantation limited to patients with inducible ventricular tachycardia enables a low overall mortality in patients with impaired LVEF.

3. academic.oup.com academic.oup.com/europace/article/7/4/327/534888

The BEta-blocker STrategy plus ICD trial - Oxford Academic The actuarial overall mortality for the CONV and EPS-guided/ICD arms was 18% vs 14% after 1 year and 29.5% vs 20% after 2 years, respectively (P = 0.3 and 0.2).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10374980/

Optimizing electrophysiology studies to prevent sudden ... This study assessed associations of minimum final extrastimulus coupling interval utilized within electrophysiology study (EPS) after myocardial infarction (MI)

5. heartlungcirc.org heartlungcirc.org/article/S1443-9506(16)30087-7/fulltext

Programmed Ventricular Stimulation to Risk Stratify for ... The primary objective of the trial is to assess whether electrophysiological study to guide prophylactic implantation of an implantable cardioverter- ...

6. academic.oup.com academic.oup.com/europace/article/25/7/euad219/7226769

Optimizing electrophysiology studies to prevent sudden ... This prospective study recruited consecutive patients with left ventricular ejection fraction (LVEF) ≤ 40% who underwent EPS days 3–5 after MI ...

7. jacc.org jacc.org/doi/10.1016/j.jacc.2014.04.008

HRS/ACC/AHA Expert Consensus Statement on the Use of ... The DINAMIT trial failed to show early survival benefits in patients who underwent ICD implantation within 6–40 days of an acute infarct.

8. ahajournals.org ahajournals.org/doi/10.1161/CIRCEP.120.008484

Long-Term Outcome of the Randomized DAPA Trial This study has shown beneficial survival impact within the first 3 years of early (<3 months) defibrillator implantation in patients with high-risk ST-segment– ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0002870325002893

Design and rationale of the PROFID EHRA randomized ... Randomized clinical trials from over 20 years ago demonstrated that an implantable cardioverter defibrillator (ICD) improved survival for patients with severely ...