Optical Coherence Tomography in Long Lesions (LONG OCT)

Optical Coherence Tomography in Long Native Coronary Artery Lesions Treated With Multiple Novel Zotarolimus-eluting Stents: LONG OCT STUDY

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 assigned to receive multiple zotarolimus eluting stents (Resolute Sprint). The completeness of stent struts coverage and/or late malapposition are evaluated by Optical Coherence Tomography at 6 months follow-up.Data will be compared to the historical arm of ODESSA trial (patients treated with multiple sirolimus-,paclitaxel polymer-or zotarolimus eluting stents).

Study Overview

• Status: Unknown
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Device: Sirolimus Eluting Stent; Device: Paclitaxel Eluting Stent; Device: Zotarolimus eluting stent; Device: Resolute Sprint

Detailed Description

It is not unknown whether overlapping drug-eluting stents provide increased vessel toxicity. 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 detects 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 assigned to receive multiple Resolute Sprint™. 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.

Obtained data will be compared with the data from a historical comparator (ODESSA trial that presented results from TAXUS Libertè™ vs Cypher Select™ vs Endeavor™ stents implanted in overlap to treat long lesions.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • BG
    • Bergamo, BG, Italy, 24128
      • Cardiovascular Department Ospedali Riuniti di Bergamo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must be at least 18 years of age
• Patient must have evidence of myocardial ischemia (e.g., stable or unstable angina, silent ischemia, positive functional study or a reversible change in the electrocardiogram (ECG) consistent with ischemia)
• Native coronary artery disease with >75% diameter stenosis (no prior stent implant, no prior brachytherapy)
• Lesion length > 20 mm
• Vessel size between 2.5 and 3.5 mm
• Multiple, overlapped Endeavor Resolute stents placement (intention to overlap > 4 mm).

Exclusion Criteria:

• Left main coronary artery disease
• Lesions in coronary artery bypass grafts
• Acute myocardial infarction
• Killip class IV
• Recent major bleeding (6 months)
• Renal failure with creatinine value > 2.5 mg/dl
• Left ventricular global ejection fraction ≤ 30%.
• Allergy to aspirin and or clopidogrel/ticlopidine
• Patient in anticoagulant therapy
• No suitable anatomy for OCT scan: (only ostial location, very tortuous anatomy, very distal or large vessels [> 3.5 mm in diameter])
• Target lesion(s) located in a major epicardial vessel or a side branch that has been previously treated with any type of percutaneous intervention (e.g., balloon angioplasty, cutting balloon, atherectomy) < 9 months prior to index procedure
• Target lesion restenotic from previous stent implantation
• Any lesion (target or non-target) that has been previously treated with brachytherapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ODESSA; ODESSA trial (NCT 00693030)Patients were randomized (2:2:2:1) to receive multiple TAXUS Libertè™ vs Cypher Select™ vs Endeavor™ vs Libertè BM stents, in overlap. At 6-months follow-up coronary angiography (QCA), IVUS and Optical Coherence Tomography assessments were made. Data reported in J. Am. Coll. Cardiol. Intv. 2010;3;531-539. DOI 10.1016/j.jcin.2010.02.008.	Device: Sirolimus Eluting Stent; Cypher stents implanted in overlap; Device: Paclitaxel Eluting Stent; Taxus stents implanted in overlap; Device: Zotarolimus eluting stent; Endeavor stents implanted in overlap
Experimental: Resolute Sprint arm; Zotarolimus Eluting stents (Resolute Sprint) implanted in overlap to treat long coronary lesions	Device: Resolute Sprint; Zotarolimus Eluting Stent (Resolute Sprint) implanted in overlap

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
In stent NIH at overlapping vs non overlapping sites	In-stent neointimal hyperplasia (NIH) thickness at 6 months, as measured by OCT, at overlapping vs non overlapping sites: superiority of Endeavor Resolute stent compared to Endeavor Sprint	6 month
Percent uncovered and malapposed struts in OCT	Proportion of stent struts uncovered and/or malapposed at 6 months, as measured by OCT, at overlapping vs non overlapping sites: non inferiority of Endeavor Resolute compared to Endeavor Sprint.	6 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of > 30% uncovered struts/total number of struts per section.		6 months
MACE Rates	All specific components of MACE (cardiac death, myocardial infarction (Q wave and non Q wave), and target vessel revascularization) will be summarized. MACE shall be assessed at, discharge (or within 7 days, whichever comes first), 1, 6 and 12 months post index procedure.	1-6 and 12 months
IVUS parameters	Based on IVUS Core Lab analysis including: Neointimal volume, stent volume, lumen volume and percent net volume obstruction; Neointimal Thickness: Neointimal hyperplasia (NIH) inside all struts (mean, median, max); Percent NIH Area= ([stent area-lumen area]/stent area) X 100; Rate of > 30% uncovered struts/total number of struts per section.	6 months
QCA Parameters	Based on Angiographic Core Lab analysis utilizing Quantitative Coronary Angiography (QCA) including: Mean lumen diameter, acute gain, late loss through 6 months, and binary restenosis (≥ 50% diameter stenosis) rate at 6 months post index procedure.	6 months

Collaborators and Investigators

• Sponsor: A.O. Ospedale Papa Giovanni XXIII
• Collaborators: Medtronic Vascular; Case Western Reserve University

Publications and helpful links

General Publications

• 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.
• Guagliumi G, Ikejima H, Sirbu V, Bezerra H, Musumeci G, Lortkipanidze N, Fiocca L, Tahara S, Vassileva A, Matiashvili A, Valsecchi O, Costa M. Impact of drug release kinetics on vascular response to different zotarolimus-eluting stents implanted in patients with long coronary stenoses: the LongOCT study (Optical Coherence Tomography in Long Lesions). JACC Cardiovasc Interv. 2011 Jul;4(7):778-85. doi: 10.1016/j.jcin.2011.04.007.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): August 1, 2009
• Study Completion (Anticipated): May 1, 2011

Study Registration Dates

• First Submitted: May 28, 2010
• First Submitted That Met QC Criteria: May 28, 2010
• First Posted (Estimate): May 31, 2010

Study Record Updates

• Last Update Posted (Estimate): May 31, 2010
• Last Update Submitted That Met QC Criteria: May 28, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: Coronary Artery Disease; Percutaneous Coronary Intervention; Drug Eluting Stent; Optical Coherence Tomography; Thrombosi; Long lesions in native vessels requiring overlap
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antifungal Agents; Paclitaxel; Sirolimus
• Other Study ID Numbers: BG-003-08