Clinical trial NCT01200693: Z-SEA-SIDE: Sirolimus Versus Everolimus Versus Zotarolimus-eluting Stent Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis
Official title: Z-SEA-SIDE: Sirolimus Versus Everolimus Versus Zotarolimus-eluting Stent Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Disease
Coronary Stenosis
Keywords: Angioplasty, Transluminal, Percutaneous Coronary
Drug-Eluting Stents
Lead sponsor: Catholic University of the Sacred Heart
Sponsor class: OTHER
First posted: 2010-09-14
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: BACKGROUND:

Bifurcated lesions are a challenging subset in percutaneous coronary interventions (PCI). The selection of the type of drug-eluting stents (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:

1. to compare in a prospective study the acute 3D angiographic results and the late clinical outcome of Sirolimus-eluting (SES) vs Everolimus-eluting (EES) vs Zotarolimus eluting stent (ZES) obtained using a provisional TAP-stenting technique.
2. to prospectively assess the clinical relevance (inducible ischemia) of suboptimal angiographic result in the SB after stenting.

METHODS TO BE APPLIED:

75 consecutive patients with bifurcated lesions undergoing PCI with the provisional T-and-small-protruding (TAP) technique with ZES implantation will be enrolled. 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 quantitative coronary angiography (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%.

For the comparison among SES and EES, data will be obtained from the randomized trial SEA-SIDE (NCT00697372).

PRIMARY STUDY END-POINTS.

1. COMPARISON BETWEEN ZES, SES AND EES:

   SB acute angiographic result; SB trouble; target bifurcation failure.
2. 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: 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:

1. to compare in a prospective 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 (EES) vs Zotarolimus-eluting stent (ZES) obtained using a provisional T-and-small-protruding (TAP) approach to treat bifurcated lesions.
2. 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:

75 consecutive patients with bifurcated lesions undergoing PCI with the provisional TAP-stenting technique with ZES implantation will be enrolled. 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 quantitative coronary angiography (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%.

For the comparison among SES and EES, data will be obtained from the randomized trial SEA-SIDE (NCT00697372).

PRIMARY STUDY END-POINTS.

1.

COMPARISON BETWEEN ZES, 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.

  2. 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).

Eligibility criteria: 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

Primary outcomes:
measure: 6-9-12-18 MONTH CLINICAL OUTCOME
timeFrame: 18 MONTHS
measure: ACUTE ANGIOGRAPHIC RESULT
timeFrame: 7 DAYS
measure: SIDE BRANCH TROUBLE
timeFrame: 7 DAYS
measure: TARGET BIFURCATION FAILURE
timeFrame: 18 MONTHS
Secondary outcomes:
measure: TECHNICAL CHARACTERISTICS
timeFrame: 7 DAYS
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Institute of Cardiology - Catholic University of Sacred Heart
Study officials:
affiliation: Catholic University of Sacred Heart
name: Francesco Burzotta, MD,PhD,FESC
role: PRINCIPAL_INVESTIGATOR
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