ACROSS-Cypher Total Occlusion Study of Coronary Arteries 4 Trial

ACROSS-Cypher® is a prospective, multi-center, open label, single arm study of the Cypher® sirolimus eluting coronary stent in native total coronary occlusion revascularization. The primary endpoint is binary angiographic restenosis at 6 months. The TOSCA-1 trial will be used as the historical control. The hypothesis is that compared with TOSCA-1 patients who were treated with the heparin-coated Palmaz Schatz stent, treatment with the Cypher® sirolimus eluting coronary stent will result in a \>50% relative reduction in 6 month restenosis within the treated segment of the target vessel.

Despite remarkable advances in the procedural and clinical outcomes of percutaneous revascularization, chronically occluded coronary arteries remain a formidable challenge and unresolved dilemma in interventional cardiology. Although a TCO is identified in approximately one-third of diagnostic cardiac catheterizations, still an attempted revascularization accounts for less than 8% of all percutaneous coronary interventions (PCI). Such a disparity between their frequency and treatment not only underscores the technical and procedural frustrations associated with these complex lesions, but also the clinical uncertainties regarding clinical benefits with conventional TCO revascularization and the ongoing inadequacies of current PCI methods for sustaining restenosis-free patency following initial success.

Until recently, few clinical investigations have been performed to support clinical benefit of TCO revascularization. In addition to relief of symptomatic ischemia, theoretical advantages have included enhanced left ventricular function, reduced predisposition to arrhythmic events, and improved tolerance of future ischemic events. In the Survival and Ventricular Enlargement (SAVE) trial, persistent occlusion of the infarct-related artery was associated with a relative risk of 1.47 in adjusted 4-year mortality (P=0.04). Since then, a limited number of studies documenting long-term outcomes following intended TCO revascularization have been performed.

This investigational protocol is designed to evaluate the safety and efficacy of the Cypher® sirolimus eluting coronary stent (Cordis Corporation, Miami Lakes, FL) in patients undergoing elective revascularization of nonacute total coronary occlusions (TCO). Specifically, approximately 200 patients will undergo Cypher® sirolimus eluting coronary stent(s) implantation following successful crossing of native total occlusions with a coronary guidewire. The study will be conducted at approximately 17 sites in North America. Patients included in this trial will be scheduled for percutaneous revascularization of a non-acute de novo TCO in a native vessel visually estimated to accommodate a ≥3.0 mm diameter angioplasty balloon. Important exclusion criteria will include recent myocardial infarction (\<72 hours) and any general contraindication to the procedure or scheduled clinical and angiographic follow-up. Patients may also undergo treatment of a non-target vessel lesion simultaneous with the index procedure within certain protocol-specified provisions. All patients will undergo planned angiographic follow-up 6 months following the index procedure to evaluate the primary endpoint of restenosis (\>50% diameter stenosis) within the treated/working length segment compared with results obtained using the same methodology among patients undergoing TCO revascularization with the heparin-coated Palmaz-Schatz coronary stent (Cordis Corporation, Miami Lakes, FL) in the Total Occlusion Study of Canada-1 (TOSCA) (1). Important secondary endpoints include the occurrence of major adverse cardiac events (MACE) and target vessel failure (TVF) at 30 days, 6 months and 12 months post-procedure. In addition, angiographic outcomes of in-stent and segment restenosis within the stent and segment will be examined. Further, patients enrolled in the trial will have clinical follow-up annually to five years.

Eligibility Criteria:
Inclusion Criteria:

* Patients age 18 years or older at time of consent
* Patients with clinical symptoms suggesting ischemic heart disease or having evidence of myocardial ischemia and scheduled for clinically indicated percutaneous revascularization
* Eligibility and consent to undergo PCI procedure
* Patient is an acceptable candidate for percutaneous transluminal coronary angioplasty,stenting,and emergency coronary artery bypass grafting
* Willing and able to sign informed consent form approved by local IRB/Ethics Committee and to follow protocol, including 6-month follow-up angiography
* At least 1 target segment meeting definition of non-acute total coronary occlusion
* High-grade native coronary stenosis
* Thrombolysis in Myocardial Infarction 0 or 1 antegrade flow
* Target occlusion successfully crossed with commercially available coronary guidewire
* Occluded segment suitable for placement of coronary stents
* Treated segment can accommodate 3.0mm or greater diameter balloon
* Segment not beyond severe tortuosity (45° or more) or excessively distal location

Exclusion Criteria:

* Patients undergoing treatment of a non-target vessel that is also a total coronary occlusion
* Patients with any history of allergy to iodinated contrast that cannot be effectively managed medically, or any known allergy to clopidogrel bisulfate (Plavix®), aspirin, heparin, ticlopidine, stainless steel, or sirolimus
* Evidence of acute myocardial infarction within 72 hours of intended treatment (Q-wave or non-Q-wave myocardial infarction having creatine kinase enzymes 2X the upper limit of normal with presence of a creatine kinase myocardial-band isoenzyme above Institution's ULN, or troponin above the Institution's ULN)
* Previous coronary interventional procedure of any kind within 3 months prior to the procedure in target vessel
* Planned interventional treatment of either target or any non-target vessel within 30 days post-procedure with a bare metal or Cypher® sirolimus eluting coronary stent
* Planned interventional treatment of either the target or any non-target vessel within 6 months post-procedure with a paclitaxel-eluting TAXUSTM stent
* Any contraindication to cardiac catheterization or to any standard concomitant therapies used during routine cardiac catheterization and PCI
* Target lesion requires planned treatment with a device after successful crossing other than PTCA prior to stent
* Patients with history of clinically significant abnormal laboratory findings including
* Current (within previous two weeks) neutropenia (\<1000 neutrophils/mm3)
* Thrombocytopenia (\<100,000 platelets/mm3)
* AST, ALT, alkaline phosphatase, or bilirubin \> 1.5XULN
* Serum creatinine \> 1.5 mg/dL
* Patients with evidence of ongoing or active clinical instability including the following
* Sustained systolic blood pressure \< 100mmHg or cardiogenic shock
* Acute pulmonary edema or severe congestive heart failure
* Suspected acute myocarditis, pericarditis, endocarditis, or cardiac tamponade
* Suspected dissecting aortic aneurysm
* Hemodynamically significant valvular heart disease, hypertrophic cardiomyopathy, restrictive cardiomyopathy, or congenital heart disease
* Target lesion involves a bifurcation including a diseased side branch 2.25mm or more in diameter requiring treatment
* Prior coronary bypass surgery of target lesion with patent bypass graft (balloon angioplasty alone, without coronary stenting, is permitted)
* History of stroke or transient ischemic attack within prior 6 months
* Female patients of childbearing potential
* Active peptic ulcer or upper gastrointestinal bleeding within prior 6 months
* History of bleeding diathesis or coagulopathy or refusal of blood transfusions
* Patients with any other pathology such as cancer, mental illness, which in the opinion of the investigator, might put the patient at risk, preclude follow-up, or in any way confound the results of the study
* Known previous medical condition yielding expected survival less than 1 year
* Patients who are unable or unwilling to comply with the protocol or not expected to complete the study period, including its follow-up requirements
* Currently participating in an investigational drug or another device study that has not completed the primary endpoint or that clinically interferes with the current study endpoints; or requires coronary angiography, intravascular ultrasound, or other coronary artery imaging procedures