Culotte Versus DK-CRUSH Technique in Non-left Main Coronary Bifurcation Lesions

Aim of study This prospective randomized multicenter study will compare the long-term safety and efficacy of Culotte stenting versus "Double Kissing" - Crush (DK-Crush) stenting in the treatment of the de-novo non-left main coronary bifurcation lesions with new generation everolimus-eluting stents.

Study hypothesis In large coronary bifurcation lesions (main vessel > 2.5mm, side branch > 2.25mm) including significant ostial side branch disease, Culotte stenting compared with DKcrush stenting reduces maximal percent diameter stenosis at the bifurcation at 9-month follow-up by 25 %.

Study design Prospective, randomized, German multicenter study.

Methods Four-hundred patients, in whom a double-stenting technique is intended for the treatment of a non-left main de-novo coronary bifurcation lesion will be randomly assigned to Culotte stenting or to DK-crush stenting with an approved drug-eluting stent (SYNERGY-Stent). As a part of usual care, patients will undergo 9-month angiographic follow-up with quantitative coronary angiography. Clinical follow-up is planned at 1 year if no angiographic follow-up is obtained.

• Stenting (Procedure): Comparison of two technical approaches in the interventional treatment on de-novo non-left main coronary lesions

Primary outcomes

• Angiographic restenosis in the bifurcation lesion by quantitative coronary analysis (QCA) [9 months post index percutaneous coronary intervention (PCI)]: For quantitative coronary angiography, changes between result at the completion of the index intervention and at 9 months follow-up will be analysed using a computer based system dedicated to bifurcation analysis, according to the standard operating procedure of the angiographic core laboratory. Quantitative angiographic measurements will be obtained of the three segments of the bifurcation lesion: the proximal and distal segment of the main branch and the side branch. We will perform measurements in the stented portion of the vessel (in-stent) and in the distal or proximal 5 mm margin (edge). In-segment analyses will comprise the in-stent and the edge area. In addition, the bifurcation angle from the analysis system will be estimated.

Secondary outcomes

• Incidence of target lesion revascularisation (TLR) [1 year]: Any revascularisation (Re-PCI or CABG) at segments treated during index procedure
• Incidence of major adverse cardiac events (MACE) [1 year]: MACE defined as death, Myocardial infarction (Q wave and Non-Q wave), emergent cardiac bypass surgery, or TLR
• Incidence of binary restenosis at any segment of the bifurcation lesion [9 months]: ≥ 50% diameter stenosis in the main and side branch
• Incidence of binary restenosis in the main and side branch [9 months]: ≥ 50% diameter stenosis in main and side branch
• Incidence of stent thrombosis (ST) [1 year]: Post-procedure thrombotic stent occlusion according to the Academic Research Consortium-criteria

Other outcomes

• Rate of device success [9 months]: Attainment of < 30% residual stenosis of the target lesion in the main and side branch
• Mean procedure time [Index Intervention]: Procedure time measured in minutes
• Mean radiation exposure [Index Intervention]: Radiation exposure measured in cGym²
• Mean volume of used contrast medium [Index Intervention]: Contrast medium measured in milliliters

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Clinical indication, evidenced by angina / angina-equivalent symptoms or documented ischemia (non-invasive imaging such as scintigraphy, stress-MRI or stress-echo; FFR or iwFR) or patients with acute coronary syndromes (NSTE-ACS).
2. Clinical indication to perform double stenting only with Synergy™ stents for a clinically significant bifurcation stenosis as judged by the operator.
3. De-novo non-Ieft main coronary bifurcation lesions - 1,1,1 or 0,1,1 according to the Medina classification - of a native coronary artery with the following reference vessel diameters: main branch > 2,5 mm; side branch > 2,25 mm. The difference between vessel diameter of the main and side branch is ≤ 1 mm.
4. The target lesion has not been previously treated with any interventional procedure.
5. The target vessel (main branch and side branch) must appear feasible for stent implantation.
6. Patient has no other coronary intervention planned within 30 days of the procedure.
7. Patient has been informed of the nature of the study and agrees to its provisions and has written informed consent as approved by the Ethics Committee.
8. Patient is willing to comply with all required post-procedure follow-up.

Exclusion Criteria:

1. Patient had an acute ST-elevation myocardial infarction within 72 h preceding the index procedure or target vessel contains intraluminal thrombus.
2. Use of any other coronary stent than Synergy™ and Synergy Megatron™ except for baiI-out situations.
3. Patient with a known hypersensitivity or contraindication to the needed antithrombotic therapy, stent type or contrast media that cannot be adequately pre-medicated.
4. Non successful treatment of other lesion during the same procedure.
5. Patient with a severe bleeding diathesis, history of recent major bleeding or stroke (≤ 6 months), coagulopathy or severe liver disease.
6. Patient has a co-morbidity (i.e. cancer) that may cause the patient to be noncompliant with the protocol, or is associated with limited life-expectancy (Iess than 1 year).
7. Patient is participating in any other clinical study with an investigational product.
8. Patient is known to be pregnant or lactating at time of inclusion.

• Results publication: Ferenc M, Gick M, Comberg T, Rothe J, Valina C, Toma A, Loffelhardt N, Hochholzer W, Riede F, Kienzle RP, Achtari A, Neumann FJ. Culotte stenting vs. TAP stenting for treatment of de-novo coronary bifurcation lesions with the need for side-branch stenting: the Bifurcations Bad Krozingen (BBK) II angiographic trial. Eur Heart J. 2016 Dec 1;37(45):3399-3405. doi: 10.1093/eurheartj/ehw345. Epub 2016 Aug 30. PMID 27578807
• Results publication: Chen SL, Xu B, Han YL, Sheiban I, Zhang JJ, Ye F, Kwan TW, Paiboon C, Zhou YJ, Lv SZ, Dangas GD, Xu YW, Wen SY, Hong L, Zhang RY, Wang HC, Jiang TM, Wang Y, Sansoto T, Chen F, Yuan ZY, Li WM, Leon MB. Clinical Outcome After DK Crush Versus Culotte Stenting of Distal Left Main Bifurcation Lesions: The 3-Year Follow-Up Results of the DKCRUSH-III Study. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1335-1342. doi: 10.1016/j.jcin.2015.05.017. PMID 26315736
• Results publication: Chen SL, Zhang JJ, Ye F, Chen YD, Lu SZ, Tan H, Patel T, Kenji K, Tamari I, Shan SJ, Zhu ZS, Lin S, Tian NL, Li XB, Liu ZZ, Lee M, Wei M, Xu YW, Yuan ZB, Qian J, Sun XW, Yang S, Chen JG, He B, Sumit S. [Comparison of DK crush with classical crush technique with drug-eluting stents for the treatment of coronary bifurcation lesions from DKCRUSH-1 study]. Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Feb;36(2):100-7. Chinese. PMID 19099943
• Results publication: Chen SL, Santoso T, Zhang JJ, Ye F, Xu YW, Fu Q, Kan J, Paiboon C, Zhou Y, Ding SQ, Kwan TW. A randomized clinical study comparing double kissing crush with provisional stenting for treatment of coronary bifurcation lesions: results from the DKCRUSH-II (Double Kissing Crush versus Provisional Stenting Technique for Treatment of Coronary Bifurcation Lesions) trial. J Am Coll Cardiol. 2011 Feb 22;57(8):914-20. doi: 10.1016/j.jacc.2010.10.023. PMID 21329837
• Results publication: Erglis A, Kumsars I, Niemela M, Kervinen K, Maeng M, Lassen JF, Gunnes P, Stavnes S, Jensen JS, Galloe A, Narbute I, Sondore D, Makikallio T, Ylitalo K, Christiansen EH, Ravkilde J, Steigen TK, Mannsverk J, Thayssen P, Hansen KN, Syvanne M, Helqvist S, Kjell N, Wiseth R, Aaroe J, Puhakka M, Thuesen L; Nordic PCI Study Group. Randomized comparison of coronary bifurcation stenting with the crush versus the culotte technique using sirolimus eluting stents: the Nordic stent technique study. Circ Cardiovasc Interv. 2009 Feb;2(1):27-34. doi: 10.1161/CIRCINTERVENTIONS.108.804658. Epub 2009 Feb 10. PMID 20031690
• Results publication: Ferenc M, Buettner HJ, Gick M, Comberg T, Rothe J, Khoury F, Valina C, Toma A, Kuebler P, Riede F, Neumann FJ. Clinical outcome after percutaneous treatment of de novo coronary bifurcation lesions using first or second generation of drug-eluting stents. Clin Res Cardiol. 2016 Mar;105(3):230-8. doi: 10.1007/s00392-015-0911-7. Epub 2015 Sep 2. PMID 26329585
• Results publication: Lee JM, Hahn JY, Kang J, Park KW, Chun WJ, Rha SW, Yu CW, Jeong JO, Jeong MH, Yoon JH, Jang Y, Tahk SJ, Gwon HC, Koo BK, Kim HS. Differential Prognostic Effect Between First- and Second-Generation Drug-Eluting Stents in Coronary Bifurcation Lesions: Patient-Level Analysis of the Korean Bifurcation Pooled Cohorts. JACC Cardiovasc Interv. 2015 Aug 24;8(10):1318-1331. doi: 10.1016/j.jcin.2015.05.014. PMID 26315734

• Study Protocol (PDF, 2020-12-01)
• Statistical Analysis Plan (PDF, 2019-12-09)