Complete Revascularization for Heart Attack & Coronary Artery Disease

(COMPLETE-2 Trial)

Recruiting at 120 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two strategies for treating heart attack patients with additional blocked arteries. It examines a physiology-guided method (using measures like blood flow) versus an angiography-guided method (using X-ray imaging) to determine treatment for these blockages. Patients who recently had a heart attack and successful treatment of the initial blockage, but still have other significant blockages, may qualify. The researchers aim to find the best way to improve heart health and prevent future issues. As an unphased trial, this study offers patients the chance to contribute to groundbreaking research that could shape future heart attack treatments.

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 these revascularization techniques are safe for heart attack and coronary artery disease patients?

Research shows that both physiology-guided and angiography-guided PCI (a procedure to open blocked heart arteries) are generally well-tolerated by patients with heart attacks and coronary artery disease. Studies have found that the physiology-guided approach leads to positive outcomes, such as fewer hospital visits for heart failure compared to treating only the immediate blockage.

For angiography-guided PCI, research indicates that treating all blocked arteries, not just the main one, can lower the risk of major heart issues. This suggests that the treatment is effective and generally safe.

Both methods use well-established heart care techniques, indicating a good safety record. However, discussing potential risks and benefits with a healthcare provider is always important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it aims to refine how we treat heart attacks and coronary artery disease by comparing two methods for clearing blocked arteries. The trial explores physiology-guided Non-Culprit-Lesion (NCL) PCI, which uses advanced measurements like RFR and FFR to accurately assess blood flow and decide which arteries need treatment. This method is more precise compared to traditional approaches that rely on visual angiography alone. By using these advanced techniques, the trial could improve how we identify and treat problematic arteries, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for heart attack and coronary artery disease?

This trial compares two methods for treating heart attack patients with multiple blocked arteries. Participants in one arm receive Angiography-guided Non-Culprit Lesion PCI. Research shows this approach tends to lead to better outcomes by lowering the chance of major heart problems compared to treating just the main blockage. Participants in the other arm receive Physiology-guided Non-Culprit Lesion PCI, which uses methods to measure blood flow in the arteries. Some studies suggest these methods do not significantly reduce risks like heart attacks or death. Overall, while both methods aim to improve heart health by addressing all blockages, current evidence supports angiography-guided treatment as more effective. ^{2 3 4 6 7}

Who Is on the Research Team?

Shamir Mehta, MD

Principal Investigator

Population Health Research Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05701358

Study Details | NCT05701358 | Physiology-guided vs ... To determine whether a strategy of physiology-guided complete revascularization is non-inferior to a strategy of angiography-guided complete revascularization ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1936879824011713

Left Anterior Descending Nonculprit Lesions and Clinical ... This study sought to compare: 1) cardiovascular outcomes among patients with an NCL in the proximal/mid-LAD to patients with an NCL in other ...

3. ahajournals.org ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.122.012867

Complete Revascularization Versus Culprit-Lesion-Only ... A strategy of complete revascularization reduced the risk of major cardiovascular events compared with culprit-lesion-only percutaneous coronary intervention.

4. jacc.org jacc.org/doi/abs/10.1016/j.jcin.2024.09.004

Left Anterior Descending Nonculprit Lesions and Clinical ... This study sought to compare: 1) cardiovascular outcomes among patients with an NCL in the proximal/mid-LAD to patients with an NCL in other locations; and 2) ...

5. withpower.com withpower.com/trial/phase-myocardial-ischemia-2-2023-915f3

Complete Revascularization for Heart Attack & Coronary Artery ... The COMPLETE trial demonstrated that routine, staged PCI of nonculprit lesions in patients with STEMI and multivessel CAD significantly reduces the risk of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10095226/

Management of Non-Culprit Lesions in STEMI Patients with ... A total of 1171 patients with STEMI and multivessel disease were randomized in the FLOWER-MI trial (FLOW Evaluation to Guide Revascularization ...

7. jacc.org jacc.org/doi/10.1016/j.jcin.2020.02.030

Evaluation and Management of Nonculprit Lesions in STEMI Results from recent randomized clinical trials suggest that complete revascularization after ST-segment elevation myocardial infarction improves outcomes.