Complete Revascularization for Heart Attack & Coronary Artery Disease

(COMPLETE-2 Trial)

Recruiting at 27 trial locations

Overseen By COMPLETE-2 Project Office

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Population Health Research Institute

Disqualifiers: CABG, Prior PCI, CTO, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

5100 Participants Needed

Trial Summary

What is the purpose of this trial?

COMPLETE-2 is a prospective, multi-centre, randomized controlled trial comparing a strategy of physiology-guided complete revascularization to angiography-guided complete revascularization in patients with acute ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) and multivessel coronary artery disease (CAD) who have undergone successful culprit lesion Percutaneous Coronary Intervention (PCI). COMPLETE-2 OCT is a large scale, prospective, multi-centre, observational, imaging study of patients with STEMI or NSTEMI and multivessel CAD in a subset of eligible COMPLETE-2 patients.

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 Angiography-guided NCL PCI, Angiography-guided Non-culprit Lesion PCI, Angiography-guided NCL PCI, Culprit Lesion–Only PCI, Physiology-guided NCL PCI, Physiology-guided Non-culprit Lesion Complete Revascularization, FFR-Guided Complete Revascularization for heart attack and coronary artery disease?

Research shows that complete revascularization, which involves treating all affected arteries, is more effective than treating only the artery causing the heart attack. This approach reduces the risk of future heart attacks and death from heart-related causes. ^{1 2 3 4 5}

Is complete revascularization for heart attack and coronary artery disease safe?

Research shows that using fractional flow reserve (FFR) to guide percutaneous coronary intervention (PCI) is associated with a lower risk of death and heart attacks compared to other methods, suggesting it is generally safe for treating coronary artery disease. ^{6 7 8 9 10}

How is the treatment Angiography-guided NCL PCI, Physiology-guided NCL PCI different from other treatments for heart attack and coronary artery disease?

This treatment is unique because it involves complete revascularization, which means treating not just the blocked artery causing the heart attack but also other narrowed arteries, using either angiography (imaging) or physiology (blood flow measurement) guidance. This approach has been shown to reduce the risk of future heart problems compared to treating only the blocked artery. ^{1 2 4 5 11}

Research Team

Shamir Mehta, MD

Principal Investigator

Population Health Research Institute

Eligibility Criteria

This trial is for heart attack patients with multivessel coronary artery disease who've had a successful PCI on the main blockage. They should have additional non-infarct-related artery narrowing and be within 72 hours post-PCI. Excluded are those with planned medical treatment only, life expectancy under 2 years, prior bypass surgery or recent non-culprit lesion PCI, among other factors.

Inclusion Criteria

I had a heart attack and received a stent within the last 3 days.

I am scheduled for a procedure to restore blood flow after my heart attack.

I have a narrowed artery in my heart that's not caused by a previous heart attack.

Exclusion Criteria

I have a completely blocked artery that is the only non-causing issue.

My heart attack was caused by a non-blockage issue, like a tear in the artery or a clot.

You have any other health, location, or social issue that would make it hard for you to take part in the study or complete a 5-year follow-up.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either physiology-guided or angiography-guided complete revascularization strategies

8-12 weeks

Observational Study

A subset of patients undergo Optical Coherence Tomography (OCT) imaging

Concurrent with treatment phase

Follow-up

Participants are monitored for cardiovascular outcomes and safety events

12 months

Treatment Details

Interventions

• Angiography-guided NCL PCI
• Physiology-guided NCL PCI

Trial Overview The COMPLETE-2 trial compares two strategies after a heart attack: one where further blockages are treated based on physiological assessment and another based solely on angiography images. The aim is to see which method is better for complete revascularization in patients with multiple vessel disease.

Participant Groups

Group I: Angiography-guided NCL PCI Experimental Treatment 1 Intervention

Patients randomized to this group will undergo routine staged PCI of all qualifying NCLs that were identified prior to randomization.

Group II: Physiology-guided Non-Culprit-Lesion (NCL) PCI Active Control 1 Intervention

Patients randomized to this group will have their physiology assessment using RFR and/or FFR of all qualifying NCLs that were identified prior to randomization. Other validated non-hyperemic physiology ratios (eg. iFR) may only be used when RFR is not available.

Angiography-guided NCL PCI is already approved in European Union, United States for the following indications:

Approved in European Union as Angiography-guided NCL PCI for:

• Acute ST-segment elevation myocardial infarction (STEMI)
• Non-ST-segment elevation myocardial infarction (NSTEMI)
• Multivessel coronary artery disease (CAD)

Approved in United States as Angiography-guided NCL PCI for:

• Acute ST-segment elevation myocardial infarction (STEMI)
• Non-ST-segment elevation myocardial infarction (NSTEMI)
• Multivessel coronary artery disease (CAD)

Who Is Running the Clinical Trial?

Population Health Research Institute

Lead Sponsor

Trials

165

Recruited

717,000+

Findings from Research

The COMPARE-ACUTE trial is designed to evaluate the effectiveness of fractional flow reserve (FFR)-guided complete revascularization compared to treating only the culprit lesion in STEMI patients with multivessel disease, involving 885 participants over a 3-year follow-up period.

This study addresses a critical clinical question regarding the management of nonculprit lesions in STEMI, as recent guidelines have shifted towards considering their treatment, but the optimal approach using FFR guidance has not yet been thoroughly investigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and rationale of the COMPARE-ACUTE trial: Fractional flow reserve-guided primary multivessel percutaneous coronary intervention to improve guideline indexed actual standard of care for treatment of ST-elevation myocardial infarction in patients with multivessel coronary disease. Smits, PC., Assaf, A., Richardt, G., et al.[2022]

The COMPLETE trial demonstrated that routine, staged PCI of nonculprit lesions in patients with STEMI and multivessel CAD significantly reduces the risk of serious outcomes, such as death from cardiovascular causes or new myocardial infarction.

This study supports the approach of complete revascularization as the standard of care for these patients, showing no major safety concerns associated with the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete or Incomplete Revascularization for ST-Segment Elevation Myocardial Infarction: The PRAMI Trial to COMPLETE. Bossard, M., Mehta, SR.[2021]

In a study of 562 patients with acute myocardial infarction and multivessel disease, 30% of those undergoing angiography-guided PCI received unnecessary treatment for non-infarct-related arteries (non-IRA) that had a quantitative flow ratio (QFR) greater than 0.80, indicating they did not need intervention.

Patients who underwent unnecessary PCI for non-IRA lesions had a significantly higher rate of major adverse cardiac events (MACEs) at 12.9% compared to just 3.1% in those who deferred treatment, highlighting the risks associated with unnecessary procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

QFR Assessment and Prognosis After Nonculprit PCI in Patients With Acute Myocardial Infarction. Lee, SH., Hong, D., Shin, D., et al.[2023]

In a systematic review of 10 randomized clinical trials involving 7030 patients, complete revascularization in STEMI patients with multivessel disease was associated with a significant reduction in cardiovascular (CV) mortality compared to treating only the culprit lesion, with an odds ratio of 0.69.

Complete revascularization also led to a lower incidence of the composite outcome of CV death or new myocardial infarction (MI), showing consistent benefits regardless of whether the procedure was guided by fractional flow reserve (FFR) or angiography.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction: A Systematic Review and Meta-analysis. Bainey, KR., Engstrøm, T., Smits, PC., et al.[2022]

In a multicenter trial involving patients with STEMI and multivessel disease, complete revascularization guided by fractional flow reserve (FFR) did not show a significant advantage over angiography-guided revascularization in reducing the risk of death, nonfatal myocardial infarction, or urgent revascularization at one year.

The study found similar rates of adverse outcomes between the two groups, with 5.5% of patients in the FFR group experiencing primary outcome events compared to 4.2% in the angiography group, indicating that both strategies are relatively safe and effective for managing multivessel disease in STEMI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. Puymirat, E., Cayla, G., Simon, T., et al.[2021]

In a study of 1109 acute coronary syndrome (ACS) patients, those who underwent multivessel percutaneous coronary intervention (PCI) had a significantly lower incidence of cardiovascular disease death and non-fatal myocardial infarction over a mean follow-up of 2.7 years compared to those who only had PCI on the culprit lesion (4.0% vs. 9.6%).

Multivessel PCI was associated with a 63% reduction in the risk of cardiovascular events, indicating that treating non-culprit lesions in ACS patients can lead to better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Multivessel Percutaneous Coronary Intervention vs. Culprit Vessel Percutaneous Coronary Intervention in Patients with Acute Coronary Syndromes and Multivessel Coronary Artery Disease. Yasuda, K., Ogita, M., Tsuboi, S., et al.[2023]

In a study of 117 patients who underwent PCI, those with complex non-culprit lesions (NCL) and a history of acute myocardial infarction (AMI) were found to have a significantly higher risk of requiring further interventions after the initial procedure.

Interestingly, the study also revealed that smoking at follow-up was associated with fewer coronary interventions, suggesting a complex relationship between smoking and cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic clinical and angiographic characteristics for the development of a new significant lesion in remote segments after successful percutaneous coronary intervention. Tsiamis, E., Toutouzas, K., Synetos, A., et al.[2016]

The study analyzed 3227 nonculprit lesions in 660 patients from the PROSPECT study, finding that a lesion-specific IVUS-FFR value of ≤0.95 was a strong predictor of major adverse cardiovascular events (MACE) over a median follow-up of 3.4 years.

Lesion-specific IVUS-FFR was identified as an independent predictor of future MACE, indicating that even minor reductions in this measurement can signal increased risk, alongside other high-risk morphological characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Intravascular Ultrasound-Derived Lesion-Specific Virtual Fractional Flow Reserve Predicts 3-Year Outcomes of Untreated Nonculprit Lesions: The PROSPECT Study. Seike, F., Mintz, GS., Matsumura, M., et al.[2023]

A meta-analysis of 26 studies involving 78,897 patients found that FFR-guided PCI significantly reduces the risk of all-cause mortality and myocardial infarction compared to non-physiology-guided revascularization methods.

Despite the benefits in mortality and MI risk, there were no significant differences in major adverse cardiac events or repeat revascularization rates between FFR-guided and non-physiology-guided approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractional flow reserve use in coronary artery revascularization: A systematic review and meta-analysis. Sanz Sánchez, J., Farjat Pasos, JI., Martinez Solé, J., et al.[2023]

In a study of 1171 patients with ST-segment-elevation myocardial infarction and multivessel disease, those who underwent percutaneous coronary intervention (PCI) for nonculprit lesions guided by fractional flow reserve (FFR) had a significantly lower rate of adverse events at 1 year (4.1%) compared to those who deferred PCI (8.1%).

The results suggest that deferring PCI for lesions with FFR >0.80 may not be safe, indicating that complete revascularization guided by FFR could lead to better clinical outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compared Outcomes of ST-Segment-Elevation Myocardial Infarction Patients With Multivessel Disease Treated With Primary Percutaneous Coronary Intervention and Preserved Fractional Flow Reserve of Nonculprit Lesions Treated Conservatively and of Those With Low Fractional Flow Reserve Managed Invasively: Insights From the FLOWER-MI Trial. Denormandie, P., Simon, T., Cayla, G., et al.[2022]

In the COMPLETE trial involving 4,041 patients with ST-segment elevation myocardial infarction, complete revascularization significantly reduced major cardiovascular events in patients with nonculprit lesions that had stenosis severity of 60% or more, showing a hazard ratio of 0.61.

Patients with less severe stenosis (less than 60%) did not experience a significant benefit from complete revascularization, indicating that the severity of nonculprit lesion stenosis is crucial for determining the efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonculprit Lesion Severity and Outcome of Revascularization in Patients With STEMI and Multivessel Coronary Disease. Sheth, T., Pinilla-Echeverri, N., Moreno, R., et al.[2023]

References

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

Design and rationale of the COMPARE-ACUTE trial: Fractional flow reserve-guided primary multivessel percutaneous coronary intervention to improve guideline indexed actual standard of care for treatment of ST-elevation myocardial infarction in patients with multivessel coronary disease. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Complete or Incomplete Revascularization for ST-Segment Elevation Myocardial Infarction: The PRAMI Trial to COMPLETE. [2021]

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

QFR Assessment and Prognosis After Nonculprit PCI in Patients With Acute Myocardial Infarction. [2023]

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

Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction: A Systematic Review and Meta-analysis. [2022]

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

Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. [2021]

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

Impact of Multivessel Percutaneous Coronary Intervention vs. Culprit Vessel Percutaneous Coronary Intervention in Patients with Acute Coronary Syndromes and Multivessel Coronary Artery Disease. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Prognostic clinical and angiographic characteristics for the development of a new significant lesion in remote segments after successful percutaneous coronary intervention. [2016]

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

Impact of Intravascular Ultrasound-Derived Lesion-Specific Virtual Fractional Flow Reserve Predicts 3-Year Outcomes of Untreated Nonculprit Lesions: The PROSPECT Study. [2023]

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

Fractional flow reserve use in coronary artery revascularization: A systematic review and meta-analysis. [2023]

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

Compared Outcomes of ST-Segment-Elevation Myocardial Infarction Patients With Multivessel Disease Treated With Primary Percutaneous Coronary Intervention and Preserved Fractional Flow Reserve of Nonculprit Lesions Treated Conservatively and of Those With Low Fractional Flow Reserve Managed Invasively: Insights From the FLOWER-MI Trial. [2022]

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

Nonculprit Lesion Severity and Outcome of Revascularization in Patients With STEMI and Multivessel Coronary Disease. [2023]