ACROSS-Cypher Total Occlusion Study of Coronary Arteries 4 Trial

This study has been completed.
Sponsor:
Collaborator:
Cordis Corporation
Information provided by (Responsible Party):
Sunil Rao, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00378612
First received: September 19, 2006
Last updated: November 13, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Coronary Occlusions
Device: Cypher sirolimus eluting coronary stent
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Approaches to Chronic Occlusions With Sirolimus Stents-Cypher (ACROSS-Cypher) Total Occlusion Study of Coronary Arteries 4 Trial

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Angiographic binary restenosis (>=50% diameter stenosis) in TCO treated/working length compared with restenosis outcomes in the Total Occlusion Study of Canada (TOSCA) [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Angiographic binary in-segment restenosis (>= 50% diameter stenosis) rate at 6 months post-procedure [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Angiographic binary in-stent restenosis (>= 50% diameter stenosis) rate at 6 months post-procedure [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • In-segment late lumen loss at 6 months [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • In-stent late lumen loss at 6 months [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Device Success [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Lesion Success [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Procedure Success [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Major Adverse Cardiac Events (MACE) rate at 30 days, 6 months, and 12 months post-procedure [ Time Frame: 30 days, 6 months and 12 months post-procedure ] [ Designated as safety issue: Yes ]
  • Target Site Revascularization (TSR) rate and clinically-driven TSR rate at 6 and 12 months post-procedure Target Vessel Revascularization (TVR) rate and clinically-driven TVR rate at 6 and 12 months post-procedure [ Time Frame: 6 and 12 months post-procedure ] [ Designated as safety issue: Yes ]
  • Target Vessel Failure (TVF) rate at 6 and 12 months post-procedure [ Time Frame: 6 and 12 months post-procedure ] [ Designated as safety issue: Yes ]
  • In-stent and in-segment minimum lumen diameter (MLD) at 6 months post-procedure [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Failure of sustained patency at 6 months (≥70% stenosis with TIMI <3 flow at follow-up angiography) [ Time Frame: 6 months post-procedure ] [ Designated as safety issue: No ]
  • Subacute thrombosis occurring within 30 days post-procedure [ Time Frame: 30 days post-procedure ] [ Designated as safety issue: Yes ]

Enrollment: 200
Study Start Date: June 2005
Study Completion Date: September 2012
Primary Completion Date: April 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cypher® sirolimus eluting coronary stent
All pts were given the Cypher sirolimus eluting coronary stent in this open-label, single-arm, non-randomized trial
Device: Cypher sirolimus eluting coronary stent
Cypher® sirolimus eluting coronary stent ranging in diameters 2.5 to 3.5 mm and available in length from 8 to 33 mm.

Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378612

Locations
United States, California
Scripps Memorial Hospital-La Jolla
La Jolla, California, United States, 92037
Green Hospital of Scripps Health
La Jolla, California, United States, 92037
United States, District of Columbia
Washington Hospital Center
Washington, District of Columbia, United States, 20010
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Brigham and Womens Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
United States, Missouri
Saint Lukes Hospital
Kansas City, Missouri, United States, 64111
United States, New York
New York Presbyterian Medical
New York, New York, United States, 10032
United States, North Carolina
The Sanger Clinic PA
Charlotte, North Carolina, United States, 28203
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
North Ohio Heart Center
Elyria, Ohio, United States, 44035
United States, Texas
Heart Hospital of Austin
Austin, Texas, United States, 78756
Canada, British Columbia
Vancouver Hospital and Health Science Centre
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Ontario
Toronto General Hospital
Toronto, Ontario, Canada, M5G 2C4
Saint Michaels Hospital
Toronto, Ontario, Canada, M5B 1W8
Sponsors and Collaborators
Sunil Rao
Cordis Corporation
Investigators
Principal Investigator: Sunil Rao, M.D. Duke University
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sunil Rao, Associate Professor, Medicine - Cardiology, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00378612     History of Changes
Other Study ID Numbers: Pro00007965, 1525004
Study First Received: September 19, 2006
Last Updated: November 13, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Duke University:
trials
stents
coronary occlusions

Additional relevant MeSH terms:
Coronary Occlusion
Coronary Disease
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 20, 2014