Clinical trial NCT00697372: SEA-SIDE: Sirolimus Versus Everolimus-eluting Stent Randomized Assessment in Bifurcated Lesions and Clinical SIgnificance of Residual siDE-branch Stenosis
Official title: SEA-SIDE: Sirolimus Versus Everolimus-eluting Stent Randomized 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: 2008-06-13
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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:

1. 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.
2. 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.

1. COMPARISON BETWEEN 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 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.
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:

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.

1. 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.
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 (Comparison of the rate of target bifurcation failure)
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
References:
citation: Colombo A, Moses JW, Morice MC, Ludwig J, Holmes DR Jr, Spanos V, Louvard Y, Desmedt B, Di Mario C, Leon MB. Randomized study to evaluate sirolimus-eluting stents implanted at coronary bifurcation lesions. Circulation. 2004 Mar 16;109(10):1244-9. doi: 10.1161/01.CIR.0000118474.71662.E3. Epub 2004 Feb 23.
citation: Ormiston JA, Webster MW, El Jack S, Ruygrok PN, Stewart JT, Scott D, Currie E, Panther MJ, Shaw B, O'Shaughnessy B. Drug-eluting stents for coronary bifurcations: bench testing of provisional side-branch strategies. Catheter Cardiovasc Interv. 2006 Jan;67(1):49-55. doi: 10.1002/ccd.20453.
citation: Pan M, Suarez de Lezo J, Medina A, Romero M, Delgado A, Segura J, Ojeda S, Mazuelos F, Hernandez E, Melian F, Pavlovic D, Esteban F, Herrador J. Drug-eluting stents for the treatment of bifurcation lesions: a randomized comparison between paclitaxel and sirolimus stents. Am Heart J. 2007 Jan;153(1):15.e1-7. doi: 10.1016/j.ahj.2006.10.017.
citation: Lefevre T, Louvard Y, Morice MC, Loubeyre C, Piechaud JF, Dumas P. Stenting of bifurcation lesions: a rational approach. J Interv Cardiol. 2001 Dec;14(6):573-85. doi: 10.1111/j.1540-8183.2001.tb00375.x.
citation: Ge L, Tsagalou E, Iakovou I, Sangiorgi GM, Corvaja N, Airoldi F, Chieffo A, Montorfano M, Michev I, Colombo A. In-hospital and nine-month outcome of treatment of coronary bifurcational lesions with sirolimus-eluting stent. Am J Cardiol. 2005 Mar 15;95(6):757-60. doi: 10.1016/j.amjcard.2004.11.030.
citation: Valgimigli M, Malagutti P, Rodriguez Granillo GA, Tsuchida K, Garcia-Garcia HM, van Mieghem CA, Van der Giessen WJ, De Feyter P, de Jaegere P, Van Domburg RT, Serruys PW. Single-vessel versus bifurcation stenting for the treatment of distal left main coronary artery disease in the drug-eluting stenting era. Clinical and angiographic insights into the Rapamycin-Eluting Stent Evaluated at Rotterdam Cardiology Hospital (RESEARCH) and Taxus-Stent Evaluated at Rotterdam Cardiology Hospital (T-SEARCH) registries. Am Heart J. 2006 Nov;152(5):896-902. doi: 10.1016/j.ahj.2006.03.029.
citation: Iakovou I, Ge L, Colombo A. Contemporary stent treatment of coronary bifurcations. J Am Coll Cardiol. 2005 Oct 18;46(8):1446-55. doi: 10.1016/j.jacc.2005.05.080. Epub 2005 Sep 28.
citation: Pan M, de Lezo JS, Medina A, Romero M, Segura J, Pavlovic D, Delgado A, Ojeda S, Melian F, Herrador J, Urena I, Burgos L. Rapamycin-eluting stents for the treatment of bifurcated coronary lesions: a randomized comparison of a simple versus complex strategy. Am Heart J. 2004 Nov;148(5):857-64. doi: 10.1016/j.ahj.2004.05.029.
citation: Ge L, Iakovou I, Cosgrave J, Agostoni P, Airoldi F, Sangiorgi GM, Michev I, Chieffo A, Montorfano M, Carlino M, Corvaja N, Colombo A. Treatment of bifurcation lesions with two stents: one year angiographic and clinical follow up of crush versus T stenting. Heart. 2006 Mar;92(3):371-6. doi: 10.1136/hrt.2005.061531. Epub 2005 Jun 17.
citation: Steigen TK, Maeng M, Wiseth R, Erglis A, Kumsars I, Narbute I, Gunnes P, Mannsverk J, Meyerdierks O, Rotevatn S, Niemela M, Kervinen K, Jensen JS, Galloe A, Nikus K, Vikman S, Ravkilde J, James S, Aaroe J, Ylitalo A, Helqvist S, Sjogren I, Thayssen P, Virtanen K, Puhakka M, Airaksinen J, Lassen JF, Thuesen L; Nordic PCI Study Group. Randomized study on simple versus complex stenting of coronary artery bifurcation lesions: the Nordic bifurcation study. Circulation. 2006 Oct 31;114(18):1955-61. doi: 10.1161/CIRCULATIONAHA.106.664920. Epub 2006 Oct 23.
citation: Koo BK, Kang HJ, Youn TJ, Chae IH, Choi DJ, Kim HS, Sohn DW, Oh BH, Lee MM, Park YB, Choi YS, Tahk SJ. Physiologic assessment of jailed side branch lesions using fractional flow reserve. J Am Coll Cardiol. 2005 Aug 16;46(4):633-7. doi: 10.1016/j.jacc.2005.04.054.
citation: Burzotta F, Gwon HC, Hahn JY, Romagnoli E, Choi JH, Trani C, Colombo A. Modified T-stenting with intentional protrusion of the side-branch stent within the main vessel stent to ensure ostial coverage and facilitate final kissing balloon: the T-stenting and small protrusion technique (TAP-stenting). Report of bench testing and first clinical Italian-Korean two-centre experience. Catheter Cardiovasc Interv. 2007 Jul 1;70(1):75-82. doi: 10.1002/ccd.21194.
citation: Gradaus R, Mathies K, Breithardt G, Bocker D. Clinical assessment of a new real time 3D quantitative coronary angiography system: evaluation in stented vessel segments. Catheter Cardiovasc Interv. 2006 Jul;68(1):44-9. doi: 10.1002/ccd.20775.
citation: Burzotta F, Trani C, Todaro D, Lanza GA, Mariani L, Tommasino A, Niccoli G, Porto I, Leone AM, Crea F. Prospective evaluation of myocardial ischemia related to post-procedural side-branch stenosis in bifurcated lesions treated by provisional approach with drug-eluting stents. Catheter Cardiovasc Interv. 2012 Feb 15;79(3):351-9. doi: 10.1002/ccd.23218. Epub 2011 Dec 12.
citation: Burzotta F, Trani C, Todaro D, Mariani L, Talarico GP, Tommasino A, Giammarinaro M, Niccoli G, Porto I, Leone AM, Mongiardo R, Mazzari MA, Schiavoni G, Crea F. Prospective randomized comparison of sirolimus- or everolimus-eluting stent to treat bifurcated lesions by provisional approach. JACC Cardiovasc Interv. 2011 Mar;4(3):327-35. doi: 10.1016/j.jcin.2010.12.005.
citation: Sgueglia GA, Burzotta F, Trani C, Todaro D, Talarico GP, Niccoli G, Porto I, Leone AM, Coluccia V, Mazzari MA, Mongiardo R, Schiavoni G, Crea F. Comparative assessment of mammalian target of rapamycin inhibitor-eluting stents in the treatment of coronary artery bifurcation lesions: the CASTOR-Bifurcation registry. Catheter Cardiovasc Interv. 2011 Mar 1;77(4):503-9. doi: 10.1002/ccd.22714.