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

Coronary Artery Disease Clinical Trial

— SEA-SIDE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00697372
• Other study ID #: P648
• Status: Completed
• Phase: Phase 4
• First received: June 11, 2008
• Last updated: June 14, 2010
• Start date: September 2007
• Est. completion date: April 2010

Study information

• Verified date: June 2010
• Source: Catholic University of the Sacred Heart
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: April 2010
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Constriction, Pathologic
• Coronary Artery Disease
• Coronary Disease
• Coronary Stenosis
• Myocardial Ischemia

Intervention

Device:
• Sirolimus eluting stent
Implantation of Sirolimus eluting stent
• Everolimus eluting stent
Implantation of Everolimus eluting stent

Locations

Country	Name	City	State
Italy	Institute of Cardiology - Catholic University of Sacred Heart	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Catholic University of the Sacred Heart

Country where clinical trial is conducted

Italy, 

References & Publications (13)

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. — View 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. Epub 2004 Feb 23. — View 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. Epub 2005 Jun 17. — View 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. — View Citation

Gradaus R, Mathies K, Breithardt G, Böcker 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. — View Citation

Iakovou I, Ge L, Colombo A. Contemporary stent treatment of coronary bifurcations. J Am Coll Cardiol. 2005 Oct 18;46(8):1446-55. Epub 2005 Sep 28. Review. — View 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. — View Citation

Lefèvre T, Louvard Y, Morice MC, Loubeyre C, Piéchaud JF, Dumas P. Stenting of bifurcation lesions: a rational approach. J Interv Cardiol. 2001 Dec;14(6):573-85. Review. — View 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. — View Citation

Pan M, de Lezo JS, Medina A, Romero M, Segura J, Pavlovic D, Delgado A, Ojeda S, Melián F, Herrador J, Ureña 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. — View Citation

Pan M, Suárez 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. — View Citation

Steigen TK, Maeng M, Wiseth R, Erglis A, Kumsars I, Narbute I, Gunnes P, Mannsverk J, Meyerdierks O, Rotevatn S, Niemelä M, Kervinen K, Jensen JS, Galløe A, Nikus K, Vikman S, Ravkilde J, James S, Aarøe J, Ylitalo A, Helqvist S, Sjögren 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. Epub 2006 Oct 23. — View 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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-9-12-18 MONTH CLINICAL OUTCOME (Comparison of the rate of target bifurcation failure)		18 MONTHS	No
Primary	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	No
Primary	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	No
Primary	TARGET BIFURCATION FAILURE	- target bifurcation failure (TBF) defined as target bifurcation-related major adverse coronary events (MACE) or target bifurcation angiographic failure.	18 MONTHS	No
Secondary	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	No