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

Coronary Artery Disease Clinical Trial

— PRECOMBAT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00422968
• Other study ID #: 2005-0012
• Status: Completed
• Phase: Phase 3
• First received: January 16, 2007
• Last updated: April 29, 2014
• Start date: March 2005
• Est. completion date: December 2013

Study information

• Verified date: April 2014
• Source: CardioVascular Research Foundation, Korea
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1454
• Est. completion date: December 2013
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Device:
• Percutaneous coronary intervention
Using silorimus eluting stent

Procedure:
• coronary artery bypass graft
coronary artery bypass graft

Locations

Country	Name	City	State
Korea, Republic of	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	Yonsei University Medical Center	Seoul
Korea, Republic of	Ajou University Hospital	Suwon
Korea, Republic of	Ulsan University Hospital	Ulsan

Sponsors (1)

Lead Sponsor	Collaborator
Seung-Jung Park

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major cardiac and cerebrovascular event (MACCE): the composite of death, myocardial infarction, stroke, and ischemica-driven target vessel revascularization		one-year after treatment	Yes
Secondary	All-cause mortality		at 30 days, 6 months, 1 year, and yearly to 5 years	Yes
Secondary	Cardiac death		at 30 days, 6 months, 1 year, and yearly to 5 years	Yes
Secondary	Myocardial infarction		at 30 days, 6 months, 1 year, and yearly to 5 years	Yes
Secondary	Cerebrovascular accident		at 30 days, 6 months, 1 year, and yearly to 5 years	Yes
Secondary	Target vessel revascularization (all and ischemia-driven)		at 30 days, 6 months, 1 year, and yearly to 5 years	No
Secondary	Target lesion revascularization (all and ischemia-driven)		at 30 days, 6 months, 1 year, and yearly to 5 years	No
Secondary	Stent thrombosis in the PCI group		at 30 days, 6 months, 1 year, and yearly to 5 years	Yes
Secondary	Binary restenosis in both in-stent and in-segment		at 9 month angiographic follow-up	No
Secondary	Graft patency and reocclusion rate		at 9 months angiographic follow-up	No
Secondary	Late luminal loss in both in-stent and in-segment		at 9 month angiographic follow-up	No