SEA-SIDE: Sirolimus Versus Everolimus-eluting Stent Randomized Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis

Study Overview
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Brief Summary
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BACKGROUND: Bifurcated lesions are a challenging subset in percutaneous coronary interventions (PCI). The selection of the type of DES and the technique for stent implantation have not been clarified. The side-branch (SB) is emerging as critical point, accounting for more than a third of the significant restenosis in the DES era. A series of data supports the adoption of a conservative strategy: stenting the main vessel (MV) only and reserving a conservative approach on the SB. Yet, the clinical relevance in terms of inducible ischemia of sub-optimal angiographic result has not been clarified. AIMS OF THE STUDY: The aims of the present study are: to compare in a prospective randomized study the acute 3D angiographic results and the late clinical outcome of Sirolimus-eluting (SES) vs Everolimus-eluting stent (EES) obtained using a provisional TAP-stenting technique. to prospectively assess the clinical relevance (inducible ischemia) of suboptimal angiographic result in the SB after stenting. METHODS TO BE APPLIED: 150 consecutive patients with bifurcated lesions undergoing PCI with the provisional TAP-stenting technique will be randomized to SES or EES implantation. Procedural and post-PCI details will be prospectively recorded. The subgroup of patients in which complete revascularization has been achieved will enter a systematic assessment of inducible ischemia by early and late exercise tests. Off line 3D QCA assessment will be performed and used to divide the study population in 2 groups according to the SB residual stenosis: Group O (optimal SB angiographic result): post-PCI SB area stenosis<50% Group S (sub-optimal SB angiographic result): post-PCI SB area stenosis>50%. PRIMARY STUDY END-POINTS. COMPARISON BETWEEN SES AND EES: SB acute angiographic result; SB trouble; target bifurcation failure. SB-RELATED ISCHAEMIA of Group O vs Group S in patients with complete revascularization: inducible ischemia at the early exercise test or occurrence of early spontaneous ischemia related to the SB.

Detailed Description
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Bifurcated lesions are challenging target lesions in percutaneous coronary interventions (PCI) which may specifically benefit from the usage of drug-eluting stents (DES). However, the selection of the type of DES and the technique for DES implantation have not been clarified. In spite of the technique adopted, the side-branch (SB) is emerging as critical point, accounting for more than a third of the significant restenosis in the DES era. A series of data supports the adoption of a conservative strategy: stenting the main vessel (MV) only and reserving a conservative approach on the SB as this is not associated with worse outcome compared to more complex stenting strategies. Yet, the clinical relevance in terms of inducible ischemia of sub-optimal angiographic result has not been clarified. AIMS OF THE STUDY: The aims of the present study are: to compare in a prospective randomized study the acute 3D angiographic results (as a measure of the impact of stent design) and the late clinical outcome of Sirolimus-eluting (SES) vs Everolimus-eluting stent (EES) obtained using a provisional TAP-stenting approach to treat bifurcated lesions. to prospectively assess the clinical relevance (in terms of inducible ischemia) of suboptimal angiographic result in the SB of bifurcated lesions treated by stenting. METHODS TO BE APPLIED: 150 consecutive patients with bifurcated lesions undergoing PCI with the provisional TAP-stenting technique will be randomized to SES or EES implantation. Procedural details, post-PCI cardiac enzyme release, clinical outcome up to 1 year will be prospectively recorded. After the procedure, the subgroup of patients in which complete revascularization has been achieved (no untreated stenosis >50% in any other vessel, no residual stenosis >50% in any other treated vessel), will enter a systematic assessment of inducible ischemia by early (<8 days) and late (6-month) exercise tests. Off line 3D QCA assessment will be performed and used to divide the study population in 2 groups according to the SB residual stenosis: Group O (optimal SB angiographic result): post-PCI SB area stenosis<50% and Group S (sub-optimal SB angiographic result): post-PCI SB area stenosis>50%. PRIMARY STUDY END-POINTS. COMPARISON BETWEEN SES AND EES: SB acute angiographic result: comparison of the 3DQCA-estimated MLD and MLA in the SB. SB trouble: composite of: 1. occurrence of SB TIMI flow <3 after MV stenting throughout the procedure; 2. need of guidewire(s) different from BMW to re-wire SB after MV stenting; 3. failure to re-wire the SB after MV stenting; 4. failure to dilate the SB after MV stenting and SB re-wiring. target bifurcation failure (TBF) defined as target bifurcation-related major adverse coronary events (MACE) or target bifurcation angiographic failure. SB-RELATED ISCHAEMIA of Group O vs Group S in patients with complete revascularization: inducible ischemia (diagnostic ST-segment changes) at the early (<8 days) exercise test or occurrence of early (<12 weeks) spontaneous ischemia related to the SB (any ischemic episode requiring unplanned coronary angiography with documentation of main vessel patency).

Official Title
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SEA-SIDE: Sirolimus Versus Everolimus-eluting Stent Randomized Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis

Conditions
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Coronary Artery Disease, Coronary Stenosis

Intervention / Treatment
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* Device: Sirolimus eluting stent
* Device: Everolimus eluting stent


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: de novo bifurcated lesions lesions >50% located in a major bifurcation point TIMI >2 on both main vessel and side branch main vessel visual diameter >2.5 mm side branch visual diameter >2.0 mm >18 years of age signed the informed consent to enter the study Exclusion Criteria: known hypersensitivity to Sirolimus, Everolimus, cobalt, chromium, nickel, tungsten acrylic and fluoro-polymers contraindications to double antiplatelet therapy acute (within 48 hours) ST-elevation acute myocardial infarction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SES<br>Patients with coronary bifurcation lesions treated by Sirolimus eluting stent | Device: Sirolimus eluting stent<br>* Implantation of Sirolimus eluting stent<br>* Other names: Cypher stent - Cordis (Johnson&Johnson Company);|
| Active Comparator: EES<br>Patients with coronary bifurcation lesions treated by Everolimus eluting stent | Device: Everolimus eluting stent<br>* Implantation of Everolimus eluting stent<br>* Other names: Xience stent - Abbot company;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-9-12-18 MONTH CLINICAL OUTCOME (Comparison of the rate of target bifurcation failure) |  | 18 MONTHS | 
| ACUTE ANGIOGRAPHIC RESULT | MV acute angiographic result: comparison of the 3DQCA-estimated MLD and MLA in the MV. SB acute angiographic result: comparison of the 3DQCA-estimated MLD and MLA in the SB. | 7 DAYS | 
| SIDE BRANCH TROUBLE | SB trouble composite of: occurrence of SB TIMI flow <3 after MV stenting throughout the procedure; need of guidewire(s) different from BMW to re-wire SB after MV stenting; failure to re-wire the SB after MV stenting; failure to dilate the SB after MV stenting and SB re-wiring. | 7 DAYS | 
| TARGET BIFURCATION FAILURE | - target bifurcation failure (TBF) defined as target bifurcation-related major adverse coronary events (MACE) or target bifurcation angiographic failure. | 18 MONTHS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TECHNICAL CHARACTERISTICS | comparison of procedural time, fluoroscopy time, total x-ray exposure, contrast media volume usage, number of guidewires used to wire the SB, direct stenting failure rate, kissing balloon rate, occurrence of transient deterioration of blood flow through the SB (TIMI<3) | 7 DAYS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Angioplasty, Transluminal, Percutaneous Coronary, Drug-Eluting Stents