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

Phase 3

Completed

• Conditions: Coronary Artery Disease
• Interventions: Device: Percutaneous coronary intervention; Procedure: coronary artery bypass graft

• Registration Number: NCT00422968
• Lead Sponsor: Seung-Jung Park

Brief Summary

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

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).

Study Timeline

• Study Start: 2005-03
• Study First Submitted: 2007-01-16
• Study First Submitted QC: 2007-01-16
• Study First Posted: 2007-01-17
• Primary Completion: 2009-11
• Study Completion: 2013-12
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-29
• Last Update Posted: 2014-05-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1454

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
percutaneous coronary intervention	Percutaneous coronary intervention	Using silorimus eluting stent
coronary artery bypass graft	coronary artery bypass graft	coronary artery bypass graft

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Myocardial infarction	at 30 days, 6 months, 1 year, and yearly to 5 years
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
Binary restenosis in both in-stent and in-segment	at 9 month angiographic follow-up
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
Late luminal loss in both in-stent and in-segment	at 9 month angiographic follow-up
Graft patency and reocclusion rate	at 9 months angiographic follow-up

Trial Locations

Locations (13)

Daegu Catholic University Medical Center; 🇰🇷 Daegu, Korea, Republic of

Chungnam National University Hospital; 🇰🇷 Daejeon, Korea, Republic of

Chonnam National University Hospital; 🇰🇷 Gwangju, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Hospital; 🇰🇷 Seoul, Korea, Republic of

St.Mary's Catholic Medical Center; 🇰🇷 Seoul, Korea, Republic of

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