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

• ClinicalTrials.gov Identifier: NCT00422968
• Recruitment Status: Completed
• First Posted: January 17, 2007
• Last Update Posted: May 1, 2014
• Sponsor: Seung-Jung Park
• Information provided by (Responsible Party): Seung-Jung Park, CardioVascular Research Foundation, Korea

Tracking Information

• First Submitted Date: January 16, 2007
• First Posted Date: January 17, 2007
• Last Update Posted Date: May 1, 2014
• Study Start Date: March 2005
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 12, 2007): Major cardiac and cerebrovascular event (MACCE): the composite of death, myocardial infarction, stroke, and ischemica-driven target vessel revascularization [ Time Frame: one-year after treatment ]

Original Primary Outcome Measures (submitted: January 16, 2007)

• The primary objective is measured in terms of major cardiac and cerebrovascular event (MACCE)-free survival at one year follow-up.
•  Death (all-cause mortality)
•  Cerebrovascular accident
•  Non-fatal myocardial infarction (Q wave and non-Q wave)
•  Ischemia-driven target vessel revascularization either percutaneous or surgical treatment

Current Secondary Outcome Measures (submitted: June 12, 2007)

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

Original Secondary Outcome Measures (submitted: January 16, 2007)

• The Composite of MACCE at 30 days, 6 months, and yearly to 5 years
• All cause death 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
• Angiographic pattern of restenosis at 9 month angiographic follow-up
• Angina status at 30 days, 6 months, 1 year, and yearly to 5 years
• Re-hospitalization with a cardiac cause

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Coronary Artery Disease

Intervention

• Device: Percutaneous coronary intervention
  Using silorimus eluting stent
• Procedure: coronary artery bypass graft
  coronary artery bypass graft

Study Arms

• Active Comparator: coronary artery bypass graft
  coronary artery bypass graft
  Intervention: Procedure: coronary artery bypass graft
• Experimental: percutaneous coronary intervention
  Using silorimus eluting stent
  Intervention: Device: Percutaneous coronary intervention

Publications *

• Jeong YJ, Ahn JM, Hyun J, Lee J, Kim JH, Yang Y, Choe K, Park H, Kang DY, Lee PH, Kang SJ, Lee SW, Kim YH, Lee CW, Park SW, Park SJ, Park DW. Ten-year Outcomes After Drug-Eluting Stents or Bypass Surgery for Left Main Coronary Disease in Patients With and Without Diabetes Mellitus: The PRECOMBAT Extended Follow-Up Study. J Am Heart Assoc. 2021 Jul 20;10(14):e019834. doi: 10.1161/JAHA.120.019834. Epub 2021 Jul 9.
• Park DW, Ahn JM, Park H, Yun SC, Kang DY, Lee PH, Kim YH, Lim DS, Rha SW, Park GM, Gwon HC, Kim HS, Chae IH, Jang Y, Jeong MH, Tahk SJ, Seung KB, Park SJ; PRECOMBAT Investigators. Ten-Year Outcomes After Drug-Eluting Stents Versus Coronary Artery Bypass Grafting for Left Main Coronary Disease: Extended Follow-Up of the PRECOMBAT Trial. Circulation. 2020 May 5;141(18):1437-1446. doi: 10.1161/CIRCULATIONAHA.120.046039. Epub 2020 Mar 30.
• Sotomi Y, Onuma Y, Cavalcante R, Ahn JM, Lee CW, van Klaveren D, de Winter RJ, Wykrzykowska JJ, Farooq V, Morice MC, Steyerberg EW, Park SJ, Serruys PW. Geographical Difference of the Interaction of Sex With Treatment Strategy in Patients With Multivessel Disease and Left Main Disease: A Meta-Analysis From SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients With Multivessel Coronary Artery Disease) Randomized Controlled Trials. Circ Cardiovasc Interv. 2017 May;10(5):e005027. doi: 10.1161/CIRCINTERVENTIONS.117.005027.
• Sotomi Y, Cavalcante R, van Klaveren D, Ahn JM, Lee CW, de Winter RJ, Wykrzykowska JJ, Onuma Y, Steyerberg EW, Park SJ, Serruys PW. Individual Long-Term Mortality Prediction Following Either Coronary Stenting or Bypass Surgery in Patients With Multivessel and/or Unprotected Left Main Disease: An External Validation of the SYNTAX Score II Model in the 1,480 Patients of the BEST and PRECOMBAT Randomized Controlled Trials. JACC Cardiovasc Interv. 2016 Aug 8;9(15):1564-72. doi: 10.1016/j.jcin.2016.04.023.
• Ahn JM, Roh JH, Kim YH, Park DW, Yun SC, Lee PH, Chang M, Park HW, Lee SW, Lee CW, Park SW, Choo SJ, Chung C, Lee J, Lim DS, Rha SW, Lee SG, Gwon HC, Kim HS, Chae IH, Jang Y, Jeong MH, Tahk SJ, Seung KB, Park SJ. Randomized Trial of Stents Versus Bypass Surgery for Left Main Coronary Artery Disease: 5-Year Outcomes of the PRECOMBAT Study. J Am Coll Cardiol. 2015 May 26;65(20):2198-206. doi: 10.1016/j.jacc.2015.03.033. Epub 2015 Mar 15.
• Park SJ, Kim YH, Park DW, Yun SC, Ahn JM, Song HG, Lee JY, Kim WJ, Kang SJ, Lee SW, Lee CW, Park SW, Chung CH, Lee JW, Lim DS, Rha SW, Lee SG, Gwon HC, Kim HS, Chae IH, Jang Y, Jeong MH, Tahk SJ, Seung KB. Randomized trial of stents versus bypass surgery for left main coronary artery disease. N Engl J Med. 2011 May 5;364(18):1718-27. doi: 10.1056/NEJMoa1100452. Epub 2011 Apr 4.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 20, 2012): 1454
• Original Enrollment (submitted: January 16, 2007): 600
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT00422968
• Other Study ID Numbers: 2005-0012
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seung-Jung Park, CardioVascular Research Foundation, Korea
• Original Responsible Party: Not Provided
• Current Study Sponsor: Seung-Jung Park
• Original Study Sponsor: CardioVascular Research Foundation
• Collaborators: Not Provided

Investigators

• Principal Investigator: Seung-Jung Park, MD, PhD; Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine

• PRS Account: CardioVascular Research Foundation, Korea
• Verification Date: April 2014