Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease

Study Overview
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Brief Summary
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The primary objective of the PRE-COMBAT trial is: To establish the safety and effectiveness of coronary stenting with the sirolimus-eluting balloon expandable stent (Cordis Johnson & Johnson, Warren, New Jersey) compared with bypass surgery for the treatment of an unprotected LMCA stenosis. The alternative hypothesis is that the experimental strategy (coronary stenting with the sirolimus-eluting stents) is not inferior to the standard strategy (bypass surgery).

Detailed Description
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Despite bypass surgery has been considered as the standard strategy for the treatment of unprotected left main coronary artery (LMCA) lesions, several studies have demonstrated that percutaneous coronary intervention (PCI) of the unprotected LMCA is feasible and appears to be an alternative strategy in selected patients. However, the safety and efficacy of PCI in patients with unprotected LMCA stenosis are still a matter of debate. Previous studies have demonstrated the safety and feasibility of unprotected LMCA intervention using bare metal stents (BMS). There was a favorable initial outcome after LMCA intervention using BMS in low-risk patients. However, in-stent restenosis after BMS implantation has emerged as the interference to widely perform PCI for unprotected LMCA lesions and the most important reason for selection of bypass surgery as the first choice for treating LMCA stenosis. In-stent restenosis in these patients not only influences long-term survival, but also make repeat intervention more complex. Despite endeavors to decrease in-stent restenosis after LMCA intervention using BMS, such as aggressive debulking atherectomy, the restenosis rate still remains at 20-30%. The sirolimus-eluting stent (SES) (Cypher, Cordis, Johnson & Johnson Corp, Miami, Florida) markedly decreases in-stent restenosis in elective patients with relatively simple coronary lesions. In real-world practice using SES, patients undergoing SES implantation were treated with a less restrictive interventional approach. However, the results are very promising similar to the randomized controlled trials. These findings warrant new studies to compare the efficacy of SES for more complex lesion subsets including LMCA disease with coronary artery bypass graft (CABG).

Official Title
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PREmier of Randomized COMparison of Bypass Surgery Versus AngioplasTy Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Device: Percutaneous coronary intervention
* Procedure: coronary artery bypass graft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient must be at least 18 years of age. Significant de novo left main stenosis (>50% by visual estimation) with or without any additional target lesions (>70% by visual estimation) Left main lesion and lesions outside LMCA (if present) potentially equally treatable with coronary stenting and bypass surgery Patients with stable (CCS class 1 to 4) or acute coronary syndromes (unstable angina pectoris Braunwald class IB, IC, IIB, IIC, IIIB, IIIC or NSTEMI) or patients with atypical chest pain or without symptoms but having documented myocardial ischemia The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site. Exclusion Criteria: The patient has a known hypersensitivity or contraindication to any of the following medications: Heparin Aspirin Both Clopidogrel and TIclopidine Sirolimus, paclitaxel, ABT 578 Stainless steel and/or Contrast media (patients with documented sensitivity to contrast which can be effectively pre-medicated with steroids and diphenhydramine [e.g. rash] may be enrolled. Patients with true anaphylaxis to prior contrast media, however, should not be enrolled). Systemic (intravenous) Sirolimus, paclitaxel or ABT-578 use within 12 months. Any previous PCI within 1 year Previous bypass surgery Any previous PCI of a LMCA or ostial left circumflex artery or ostial left anterior descending artery lesion within 1 year Intention to treat more than one totally occluded major epicardial vessel Acute MI patients within 1 week Patients with EF<30%. Patients with cardiogenic shock Any disabled stroke with neurological deficit or any cerebrovascular accident within 6 months Creatinine level > 2.0mg/dL or dependence on dialysis. Severe hepatic dysfunction (AST and ALT > 3 times upper normal reference values). Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery within 2 months. History of bleeding diathesis or known coagulopathy (including heparin-induced thrombocytopenia), or will refuse blood transfusions. Current known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL. An elective surgical procedure is planned that would necessitate interruption of thienopyridines during the first 1 year post enrollment. Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment). Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period. Subject unable or unwilling to follow-up with visits required by protocol Female of childbearing potential, unless a recent pregnancy test is negative, who possibly plan to become pregnant any time after enrollment into this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: coronary artery bypass graft<br>coronary artery bypass graft | Procedure: coronary artery bypass graft<br>* coronary artery bypass graft<br>|
| Experimental: percutaneous coronary intervention<br>Using silorimus eluting stent | Device: Percutaneous coronary intervention<br>* Using silorimus eluting stent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major cardiac and cerebrovascular event (MACCE): the composite of death, myocardial infarction, stroke, and ischemica-driven target vessel revascularization |  | one-year after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Cardiac death |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Myocardial infarction |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Cerebrovascular accident |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Target vessel revascularization (all and ischemia-driven) |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Target lesion revascularization (all and ischemia-driven) |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Stent thrombosis in the PCI group |  | at 30 days, 6 months, 1 year, and yearly to 5 years | 
| Binary restenosis in both in-stent and in-segment |  | at 9 month angiographic follow-up | 
| Graft patency and reocclusion rate |  | at 9 months angiographic follow-up | 
| Late luminal loss in both in-stent and in-segment |  | at 9 month angiographic follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary artery disease, Stent, Bypass surgery, coronary artery