The European Bifurcation Club Randomized Trial of Stepwise Provisional Stenting Versus Drug Coated Balloon Therapy for Non-left Main True Coronary Bifurcations

Official title

The European Bifurcation Club Randomized Trial of Stepwise Provisional Stenting Versus Drug Coated Balloon Therapy for Non-left Main True Coronary Bifurcations - EBC DCB Study

Overview

Clinical outcomes are worse in patients with coronary artery bifurcation lesions, even if commonly encountered in clinical practice. The use of drug coated balloons within bifurcation lesions offers the acute advantage of a more straightforward procedure, without recrossing and deformation of a stent. Thus, the primary objective of this study is to determine if Drug Coated Balloon treatment of non-left main true coronary artery bifurcation lesions is non-inferior (similar) to a provisional strategy with Drug Eluted Stent deployment.

Detailed description

The EBC DCB study is an investigator-initiated, prospective, multi-centre, open-label, randomized (1:1) non-inferiority trial.

Patients with non-left main bifurcations requiring revascularisation and both the main vessel and side branch significantly diseased ( ≥2.5mm and Medina 1/1/1, 1/0/1 or 0/1/1), constitute the source population. Patients with no more than two additional coronary disease may be considered for the study, with only one bifurcation lesion included.

Patients, pre-selected by their referring physicians, will be screened for eligibility by the study team. If patients fulfill all inclusion and do not meet exclusion criteria, they will be informed about the study's purpose and course and will be asked for participation and written informed consent. 20 sites will be involved, in 7 European countries and South Korea, for a total of 750 patients. After a 2-years recruitment period, the trial will include a Follow-Up period at 6-months, 1-year, 3-years, 5-years and 8-years. The 1-year check point will constitute the primary endpoint where the Bifurcation Orientated Composite Endpoint (BOCE) will be analyzed for non-inferiority (further analysis for superiority, if non-inferiority met).

Interventions

• Procedure Percutaneous Coronary Angioplasty
  A Percutaneous Coronary Intervention is used in both arms, with the drug Zotarolimus for stenting strategy and Paclitaxel for balloon strategy. Coronary guide wires are passed into both the distal main vessel (distal MV) and side branch (SB) and predilation of MV on a 1:1 basis is required. The device component dilates the vessel lumen by Percutaneous Transluminal Coronary Angioplasty (PTCA), while the drug is intended to reduce the proliferative response associated with restenosis.
• Device Stepwise Provisional Stent Strategy
  In the stepwise provisional stent strategy, stenting of the MV is undertaken with a wire jailed in the SB. Then, non-compliant balloons sized to the diameter of the distal MV and SB are sequentially inflated at high pressure, and then simultaneously at low pressure (kissing balloon inflation ; KBI).
• Device Drug Coated Balloon Strategy
  In the drug coated balloon (DCB) strategy, SB is prepared with a balloon at a 1:1 diameter, followed with a 1:1 sized DCB inflation for 60 seconds at nominal pressure. Then, MV is re-evaluated and treated with DCB at nominal pressure only, sized 1:1 with the proximal MV, for 60 seconds.
• Device Cross-Over Stepwise Provisional Stent Strategy
  Following Drug Coated Balloon treatment in the Main vessel (MV) in the Drug Coated Balloon Arm, if the result is unacceptable in the MV, with either TIMI\>3 flow and/or dissection propagation, MV stenting is mandatory followed with Kissing Balloon Inflation (KBI), where non-compliant balloons sized to the diameter of the distal main and side branch are sequentially inflated at high pressure, and then simultaneously at low pressure. If the cross-over stent implantation in the MV is used, a furthe

Primary outcome measures

• Bifurcation Orientated Composite Endpoint (BOCE) [Time frame: At 1-year, after the day of enrollment]

Secondary outcome measures (7)

• Bifurcation Orientated Composite Endpoint (BOCE) [Time frame: At 3, 5 and 8-years]
• Individual components of the Primary Endpoint [Time frame: At 1, 3, 5 and 8-years]
• Safety Composite Endpoint [Time frame: At 1, 3, 5 and 8-years]
• Individual components of the Safety Composite Endpoint [Time frame: At 1, 3, 5 and 8-years]
• BARC 3 or 5 bleeding rate [Time frame: At 1, 3, 5 and 8-years]
• Angina status [Time frame: At 1, 3, 5 and 8-years]
• Angina index [Time frame: At 1, 3, 5 and 8-years]

Eligibility criteria

Inclusion criteria

• True non-left main bifurcation disease with both MV and SB involvement (i.e Medina 1/1/1, 1/0/1, 0/1/1)
• Bifurcation lesion responsible for an acute or chronic coronary syndrome with at least one of the following:

• ≥70% angiographic MV and SB diameter stenosis
• Positive non-invasive testing for ischaemia
• Positive coronary physiology for ischaemia
• Significant SB as described by diameter stenosis ≥50% and all of the following:

• SB length ≥73mm
• SB diameter ≥2.5mm
• Absence of another SB emerging distally from the MV
• Non-dominant circumflex artery, if SB is a diagonal branch.

Exclusion criteria

• Patients <18 years old
• STEMI <48 hours
• Cardiogenic shock
• Chronic total occlusion involving target bifurcation vessels
• In-stent restenosis
• Patient life expectancy <12 months
• >2 other coronary lesions (target or non-target) planned for treatment
• SYNTAX score >32
• Platelet count ≤50x109/mm3
• Left ventricular ejection fraction ≤20%
• Participation in another investigational drug or device study
• Patient unable to give informed consent

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Jeger RV, Farah A, Ohlow MA, Mangner N, Mobius-Winkler S, Leibundgut G, Weilenmann D, Wohrle J, Richter S, Schreiber M, Mahfoud F, Linke A, Stephan FP, Mueller C, Rickenbacher P, Coslovsky M, Gilgen N, Osswald S, Kaiser C, Scheller B; BASKET-SMALL 2 Investigators. Drug-coated balloons for small coronary artery disease (BASKET-SMALL 2): an open-label randomised non-inferiority trial. Lancet. 2018 S PMID 30170854
• Ellis SG, Kereiakes DJ, Metzger DC, Caputo RP, Rizik DG, Teirstein PS, Litt MR, Kini A, Kabour A, Marx SO, Popma JJ, McGreevy R, Zhang Z, Simonton C, Stone GW; ABSORB III Investigators. Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease. N Engl J Med. 2015 Nov 12;373(20):1905-15. doi: 10.1056/NEJMoa1509038. Epub 2015 Oct 12. PMID 26457558
• Hildick-Smith D, Behan MW, Lassen JF, Chieffo A, Lefevre T, Stankovic G, Burzotta F, Pan M, Ferenc M, Bennett L, Hovasse T, Spence MJ, Oldroyd K, Brunel P, Carrie D, Baumbach A, Maeng M, Skipper N, Louvard Y. The EBC TWO Study (European Bifurcation Coronary TWO): A Randomized Comparison of Provisional T-Stenting Versus a Systematic 2 Stent Culotte Strategy in Large Caliber True Bifurcations. Circ PMID 27578839
• Hildick-Smith D, de Belder AJ, Cooter N, Curzen NP, Clayton TC, Oldroyd KG, Bennett L, Holmberg S, Cotton JM, Glennon PE, Thomas MR, Maccarthy PA, Baumbach A, Mulvihill NT, Henderson RA, Redwood SR, Starkey IR, Stables RH. Randomized trial of simple versus complex drug-eluting stenting for bifurcation lesions: the British Bifurcation Coronary Study: old, new, and evolving strategies. Circulation. PMID 20194880
• Konishi H, Habara M, Nasu K, Koshida R, Kinoshita Y, Tsuchikane E, Terashima M, Matsubara T, Suzuki T. Impact of Optimal Preparation Before Drug-Coated Balloon Dilatation for De Novo Lesion in Patients With Coronary Artery Disease. Cardiovasc Revasc Med. 2022 Feb;35:91-95. doi: 10.1016/j.carrev.2021.03.012. Epub 2021 Mar 20. PMID 33766488
• Jeger RV, Eccleshall S, Wan Ahmad WA, Ge J, Poerner TC, Shin ES, Alfonso F, Latib A, Ong PJ, Rissanen TT, Saucedo J, Scheller B, Kleber FX; International DCB Consensus Group. Drug-Coated Balloons for Coronary Artery Disease: Third Report of the International DCB Consensus Group. JACC Cardiovasc Interv. 2020 Jun 22;13(12):1391-1402. doi: 10.1016/j.jcin.2020.02.043. Epub 2020 May 27. PMID 32473887
• Ninomiya K, Serruys PW, Colombo A, Reimers B, Basavarajaiah S, Sharif F, Testa L, Di Mario C, Nerla R, Ding D, Huang J, Kotoku N, Kageyama S, Kageyama M, Sevestre E, Fezzi S, Dijkstra J, O'Leary N, Morel MA, Garg S, Cortese B, Onuma Y. A Prospective Randomized Trial Comparing Sirolimus-Coated Balloon With Paclitaxel-Coated Balloon in De Novo Small Vessels. JACC Cardiovasc Interv. 2023 Dec 11;16(23 PMID 37877914
• Latib A, Agostoni P, Dens J, Patterson M, Lancellotti P, Tam FCC, Schotborgh C, Kedhi E, Stella P, Shen C, Wetzels G, Testa L; PREVAIL Study Investigators. Paclitaxel Drug-Coated Balloon for the Treatment of De Novo Small-Vessel and Restenotic Coronary Artery Lesions: 12-Month Results of the Prospective, Multicenter, Single-Arm PREVAIL Study. J Invasive Cardiol. 2021 Nov;33(11):E863-E869. doi: 10. PMID 34433695

Identifiers

NCT: NCT06822322 · EBC DCB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗