POLish Bifurcation Optimal Treatment Strategy Study for Left Main Bifurcation Percutaneous Coronary Intervention (PCI)

• BiOSS LIM C (Device), also known as ALEX Plus, XIENCE: The BiOSS LIM C (Bifurcation Optimization Stent System, Balton, Warsaw, Poland). The BiOSS LIM C is a dedicated bifurcation stent covered with a mixture of a biodegradable polymer and the antiproliferative substance sirolimus. BiOSS LIM C will be used for treatment of the Left-Main bifurcation, according to its instructions for use. The Alex-Plus cobaltchromium sirolimus eluting stent (Balton, Warsaw, Poland) will be used for treatment of distal left-main side branches according to its instructions for use (i.e. proximal segments of the left anterior descending and left circumflex arteries as well as the ramus intermedius if the latter vessel is part of a trifurcation). All other lesions (other than left-main bifurcations) will be treated with XIENCE family everolimus-eluting coronary stent systems.

Primary outcomes

• Non-inferiority Comparison of Patient-oriented Composite Endpoint (PoCE) of BiOSS LIM C to a Pre-specified Objective Performance Goal (OPC). [12 months]: POCE defined as a composite measure of: All-cause mortality, Stroke (Modified Ranking Scale (mRS) ≥1), Any Myocardial infarction (MI) (includes non target vessel territory), Any unplanned revascularization for ischemia (includes all target and nontarget vessels). OPC based on data collected in Excel-study. The safety and efficacy of the BiOSS LIM C® stent with respect to a PoCE at 12 months in a real world LM bifurcation population compared with a pre-specified performance goal was not confirmed. The POLBOS LM study showed that the BiOSS LIM C® stent was not non-inferior to the XIENCE stent for percutaneous treatment of the LM disease.

Secondary outcomes

• Patient-oriented Composite Endpoint (PoCE) [12 months]: PoCE is defined as a composite of all-cause death, stroke, any MI, and any revascularization
• Target Vessel Failure [12 months]: Target Vessel Failure is defined as the composite of cardiac death, target vessel MI, and clinically indicated target vessel revascularization
• Target Lesion Failure [12 months]: Target Lesion Failure is defined as a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization
• Mortality [12 months]: Occurrence of death of any cause
• Stroke [12 months]: Occurrence of stroke (with a modified Rankin Scale >=1)
• Myocardial Infarction [12 months]: Occurrence of myocardial infarction
• Revascularization [12 months]: Occurrence of any revascularization (percutaneous coronary intervention or coronary artery bypass grafting)
• Stent Thrombosis [12 months]: Occurrence of any stent thrombosis according to standard definitions provided by the Academic Research Consortium

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patient has distal unprotected Left-Main coronary artery (ULMCA) disease with angiographic diameter stenosis (DS) ≥50% requiring revascularization.
* Left-Main Medina classification 100, 110, 101, 011, 010, 111
* Clinical and anatomic eligibility for PCI as agreed by the local Heart Team including anatomic SYNTAX Score (<33).
* Distal left main reference vessel diameter ≥3.0 mm and ≤5.5 mm. All target lesions must be located in a native coronary artery.
* Patient with silent ischemia, chronic stable angina or stabilized acute coronary syndromes with normal cardiac biomarker values
* Able to understand and provide informed consent and comply with all study procedures including follow-up

Exclusion Criteria:

* Prior PCI of the left main bifurcation at any time prior to enrollment
* Currently participating in another trial and not yet at its primary endpoint.
* Prior PCI of any other (non left main bifurcation) coronary artery lesion within 6 months (<6 months) prior to enrollment.
* Left-Main Medina classification 001.
* Any segment of the left main bifurcation (distal left main, ostial Left Anterior Descending Artery (LAD) or ostial Left Circumflex Artery (LCX) presenting with a chronic total occlusion, or containing a visible thrombus.
* Excessive angulation of the left main bifurcation (i.e. an angulation >90° between proximal LAD and proximal LCX)
* Direct stenting of the left main bifurcation
* Prior Coronary Artery Bypass Surgery (CABG) at any time prior to enrollment
* Patient requiring or may require additional surgery (cardiac or non-cardiac) within one year
* Ongoing myocardial infarction or recent myocardial infarction with cardiac biomarker levels still elevated.
* Known renal insufficiency (e.g. serum creatinine >2.5mg/dL, or creatinine clearance ≤30mL/min, or patient on dialysis).
* Known contraindication or hypersensitivity to sirolimus, everolimus, cobalt-chromium, or to medications such as aspirin, heparin, bivalirudin, and all of the following four medications: clopidogrel bisulfate, ticlopidine, prasugrel, ticagrelor.
* Patients unable to tolerate, obtain or comply with dual antiplatelet therapy for at least 12 months.
* Patient is a woman who is pregnant or nursing (a pregnancy test must be performed within 7 days prior to the index procedure in women of child-bearing potential).
* Concurrent medical condition with a life expectancy of less than 12 months.
* The patient is unwilling/not able to return for outpatient clinic at 12 month follow-up.
* Currently participating in another trial and not yet at its primary endpoint.

Participant flow

Outcome results

• Non-inferiority Comparison of Patient-oriented Composite Endpoint (PoCE) of BiOSS LIM C to a Pre-specified Objective Performance Goal (OPC). (Primary), Number, Percentage of participants: BiOSS LIM C Arm 38.0
• Patient-oriented Composite Endpoint (PoCE) (Secondary), Number, Percentage of participants: BiOSS LIM C 38.0
• Target Vessel Failure (Secondary), Number, Percentage of participants: BiOSS LIM C 28.5
• Target Lesion Failure (Secondary), Number, Percentage of participants: BiOSS LIM C 27.7
• Mortality (Secondary), Number, Percentage of participants: BiOSS LIM C 1.6
• Stroke (Secondary), Number, Percentage of participants: BiOSS LIM C 1.6
• Myocardial Infarction (Secondary), Number, Percentage of participants: BiOSS LIM C 19.0
• Revascularization (Secondary), Number, Percentage of participants: BiOSS LIM C 20.3
• Stent Thrombosis (Secondary), Number, Percentage of participants: BiOSS LIM C 0.8

Adverse events

Time frame: From enrollment until end of follow-up, up to 12 months.

Serious adverse events by term

Limitations and caveats: The original sample was intended at 260 but the study only enrolled 130 participants since it was terminated prematurely due to COVID-19, safety concerns, and discontinuation of financial support.

• Study Protocol and Statistical Analysis Plan (PDF, 2018-10-02)

• Robert Gil, Prof., Principal investigator, Central Clinical Hospital of the Ministry of Interior in Warsaw