Optical Coherence Tomography for Drug Eluting Stent Safety

Coronary Artery Disease Clinical Trial

— ODESSA  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00693030
• Other study ID #: 0106
• Status: Recruiting
• Phase: Phase 4
• First received: June 4, 2008
• Last updated: June 5, 2008
• Start date: August 2006
• Est. completion date: December 2008

Study information

• Verified date: June 2008
• Source: A.O. Ospedale Papa Giovanni XXIII
• Contact: Monia Lorini, MD
• Phone: 39-03-526-9751
• Email: mlorini[@]ospedaliriuniti.bergamo.it
• Is FDA regulated: No
• Health authority: Italy: Ethics CommitteeItaly: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 77
• Est. completion date: December 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia

Intervention

Device:
• sirolimus drug eluting coronary stent Cypher™ (Cordis Corp, Johnson & Johnson Co)
comparison of multiple drug eluting stents
• paclitaxel polymer drug eluting stent Taxus Libertè™ (Boston Scientific, Natick MS)
comparison of multiple drug eluting coronary stents
• zotarolimus drug eluting coronary stent Endeavor™ (Medtronic, Santa Rosa, CA)
comparison of multiple drug eluting coronary stents
• Libertè bare metal coronary stent Libertè™ BMS(Boston Scientific, Natick, MS)
comparison of DES in overlap vs BMS in overlap

Locations

Country	Name	City	State
Italy	Cardiovascular Department Ospedali Riuniti di Bergamo	Bergamo

Sponsors (4)

Lead Sponsor	Collaborator
A.O. Ospedale Papa Giovanni XXIII	Boston Scientific Corporation, Case Western Reserve University, Medtronic Vascular

Country where clinical trial is conducted

Italy, 

References & Publications (9)

Bouma BE, Tearney GJ, Yabushita H, Shishkov M, Kauffman CR, DeJoseph Gauthier D, MacNeill BD, Houser SL, Aretz HT, Halpern EF, Jang IK. Evaluation of intracoronary stenting by intravascular optical coherence tomography. Heart. 2003 Mar;89(3):317-20. — View 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. Epub 2007 Apr 16. — View 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. Epub 2005 Jul 5. — View Citation

Finn AV, Nakazawa G, Joner M, Kolodgie FD, Mont EK, Gold HK, Virmani R. Vascular responses to drug eluting stents: importance of delayed healing. Arterioscler Thromb Vasc Biol. 2007 Jul;27(7):1500-10. Epub 2007 May 17. Review. — View 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. Epub 2006 May 5. — View Citation

Matsumoto D, Shite J, Shinke T, Otake H, Tanino Y, Ogasawara D, Sawada T, Paredes OL, Hirata K, Yokoyama M. Neointimal coverage of sirolimus-eluting stents at 6-month follow-up: evaluated by optical coherence tomography. Eur Heart J. 2007 Apr;28(8):961-7. Epub 2006 Nov 29. — View Citation

Nakazawa G, Finn AV, John MC, Kolodgie FD, Virmani R. The significance of preclinical evaluation of sirolimus-, paclitaxel-, and zotarolimus-eluting stents. Am J Cardiol. 2007 Oct 22;100(8B):36M-44M. Review. — View 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. Epub 2007 Feb 23. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of uncovered and/or malapposed stent struts at overlapping versus non overlapping sites in drug eluting vs bare metal stents		6 months	Yes
Secondary	Ischemia Driven Target Vessel Failure		12 months	Yes
Secondary	Number of uncovered and/or malapposed stent struts at overlapping sites in sirolimus-, paclitaxel- or zotarolimus eluting stents		6 months	Yes