Clinical trial NCT00693030: Optical Coherence Tomography for Drug Eluting Stent Safety
Official title: In-Vivo Vascular Response of Sirolimus-,Paclitaxel- and Zotarolimus-Eluting Stents in Long Lesions Requiring Overlapping. A Prospective, Randomized, Controlled Study Using Optical Coherence Tomography
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Coronary Artery Disease
Keywords: Coronary Artery Disease
Percutaneous Coronary Interventions
Drug-Eluting stents
Optical Coherence Tomography
Thrombosis
Long lesions in native vessel requiring stents in overlap
Lead sponsor: A.O. Ospedale Papa Giovanni XXIII
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
name: Medtronic Vascular
name: Boston Scientific Corporation
First posted: 2008-06-06
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Increasing lesion complexity in percutaneous coronary interventions (PCI) has warranted the use of overlapping drug-eluting stents. Whether the substantial impairment of arterial healing observed at sites of overlap in preclinical pathologic studies persists in patients undergoing PCI is unknown. Consecutive patients with long lesions in native coronary vessels requiring stents in overlap are prospectively randomized to receive multiple sirolimus-,paclitaxel polymer-or zotarolimus eluting stents versus bare metal stents. The completeness of stent struts coverage and/or late malapposition are evaluated by Optical Coherence Tomography at 6 months follow-up

Detailed description: If overlapping drug-eluting stents provide increased vessel toxicity is not known. Given the association of delayed healing and incomplete endothelialization observed in animal and human autopsy studies at overlapping sites it is unclear why most patients do well with multiple DES implanted. OCT detecs smaller degrees of in-stent neointima more accurately than IVUS and might be a useful method for identify strut coverage and/or malapposition.

Patients if eligible on the basis of clinical and angiographic criteria, are randomized (2:2:2:1) to receive multiple TAXUS Libertè™ vs Cypher Select™ vs Endeavor™ vs Libertè BM stents, in overlap. Stent implantation are done accordingly to the normal interventional practice. QCA and IVUS are performed at the end of optimal stents placement per visual judgement (residual stenosis \< 10%, TIMI 3 flow). Stent, lumen size and volume as well as complete stent strut apposal will be determined by IVUS analysis. Clinical follow-up will take place at 1 month (±1 week), 6 months (±2 weeks) and 1 year (±2 weeks). At 6-months follow-up all patients will undergo a quantitative coronary angiography (QCA), IVUS and Optical Coherence Tomography (LightLab OCT Imaging M2, automated pull back and flushing combination)assessments.

OCT images will be acquired at 15-30 frames per second. Blind corelab quantitative strut by strut analysis will be performed using a novel dedicated software at each 0.5 mm section. The following OCT variables will be evaluated:number of visualized strut per section, mean-max neointimal thickness per section, % struts well apposed with neointima at overlapping vs non overlapping sites, % struts without neointima, % struts malapposed, rate of \> 30% uncovered struts/total number of struts per section.

Eligibility criteria: Inclusion Criteria:

1. Native coronary artery disease with ≥ 75% diameter stenosis
2. Lesion length ≥ 20 mm,
3. Vessel size in between 2.5 and 3.5 mm.
4. Multiple, overlapped DES vs BMS placement (intention to overlap ≥ 4 mm)
5. Signed patient informed consent

Exclusion Criteria:

1. left main coronary artery disease,
2. lesions in coronary artery bypass grafts,
3. acute myocardial infarction,
4. poor cardiac function as defined by left ventricular global ejection fraction ≤ 30%.
5. allergy to aspirin and or clopidogrel/ticlo,
6. renal failure with creatinine value \> 2.5,
7. no suitable anatomy for OCT scan

Primary outcomes:
measure: Number of uncovered and/or malapposed stent struts at overlapping versus non overlapping sites in drug eluting vs bare metal stents
timeFrame: 6 months
Secondary outcomes:
measure: Ischemia Driven Target Vessel Failure
timeFrame: 12 months
measure: Number of uncovered and/or malapposed stent struts at overlapping sites in sirolimus-, paclitaxel- or zotarolimus eluting stents
timeFrame: 6 months
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Cardiovascular Department Ospedali Riuniti di Bergamo
Study officials:
affiliation: Cardiovascular Department Ospedali Riuniti di Bergamo
name: Giulio Guagliumi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006 Jul 4;48(1):193-202. doi: 10.1016/j.jacc.2006.03.042. Epub 2006 May 5.
citation: Finn AV, Kolodgie FD, Harnek J, Guerrero LJ, Acampado E, Tefera K, Skorija K, Weber DK, Gold HK, Virmani R. Differential response of delayed healing and persistent inflammation at sites of overlapping sirolimus- or paclitaxel-eluting stents. Circulation. 2005 Jul 12;112(2):270-8. doi: 10.1161/CIRCULATIONAHA.104.508937. Epub 2005 Jul 5.
citation: Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007 May 8;115(18):2435-41. doi: 10.1161/CIRCULATIONAHA.107.693739. Epub 2007 Apr 16.
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citation: Takano M, Inami S, Jang IK, Yamamoto M, Murakami D, Seimiya K, Ohba T, Mizuno K. Evaluation by optical coherence tomography of neointimal coverage of sirolimus-eluting stent three months after implantation. Am J Cardiol. 2007 Apr 15;99(8):1033-8. doi: 10.1016/j.amjcard.2006.11.068. Epub 2007 Feb 23.
citation: Yamaguchi T, Terashima M, Akasaka T, Hayashi T, Mizuno K, Muramatsu T, Nakamura M, Nakamura S, Saito S, Takano M, Takayama T, Yoshikawa J, Suzuki T. Safety and feasibility of an intravascular optical coherence tomography image wire system in the clinical setting. Am J Cardiol. 2008 Mar 1;101(5):562-7. doi: 10.1016/j.amjcard.2007.09.116. Epub 2008 Jan 10.
citation: Guagliumi G, Musumeci G, Sirbu V, Bezerra HG, Suzuki N, Fiocca L, Matiashvili A, Lortkipanidze N, Trivisonno A, Valsecchi O, Biondi-Zoccai G, Costa MA; ODESSA Trial Investigators. Optical coherence tomography assessment of in vivo vascular response after implantation of overlapping bare-metal and drug-eluting stents. JACC Cardiovasc Interv. 2010 May;3(5):531-9. doi: 10.1016/j.jcin.2010.02.008.