Clinical trial NCT01925794: COBRA PZF™ Coronary Stent for Early Healing, Thrombus Inhibition, Endothelialization and Avoiding Long-Term DAPT
Official title: COBRA PZF™ Coronary Stent System in Native Coronary Arteries for Early Healing, Thrombus Inhibition, Endothelialization and Avoiding Long-Term Dual Anti-Platelet Therapy. The PzF Shield Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Disease
Keywords: Stent, Coronary Arteries for Early healing
Lead sponsor: CeloNova BioSciences, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-20
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a prospective, multi-center, non-randomized, single arm clinical trial that will be conducted at up to 40 sites in the United States and Outside United States (OUS). This study will enroll patients with symptomatic ischemic heart disease due to a single de novo lesion contained within a native coronary artery with reference vessel diameter between 2.5 mm and 4.0 mm and lesion length ≤ 24 mm that is amenable to percutaneous coronary intervention (PCI) and stent deployment. All patients will be followed at 30 days, 6 months, 9 months, 1 year and annually for 5 years post index stenting procedure.

Detailed description: The main objective of this study is to evaluate the safety and effectiveness of the COBRA PzF™ Coronary Stent System in the treatment of de novo lesions in native coronary arteries. The primary endpoint will be the incidence of target vessel failure (TVF, see definition below) within 270 days of treatment with the COBRA PzFTM Coronary Stent System. This rate will be compared to a performance goal derived using a meta-analysis from published historical data of the standard-of-care therapy, coronary stenting with bare metal stents.

PRIMARY STUDY HYPOTHESIS The CeloNova COBRA PzFTM Study will have a primary endpoint (TVF) rate less than 19.62% and by that will meet the performance goal for bare metal stents, per the results of the historical control group combined with relevant data for EXPRESS™, Driver™, Presillion/Presillion plus™ and NIRFLEX™ stents.

SECONDARY STUDY HYPOTHESIS The powered secondary endpoint for this trial is that the CeloNova COBRA PzFTM Study will have a 9-month in-stent late loss (LL) that meets or is lower than the performance goal of 1.1 mm.

NUMBER OF PATIENTS 296 patients will be enrolled to account for loss to follow-up, which is estimated to be approximately 5% (resulting in 281 evaluable patients), at up to 40 sites in United States and OUS. At least 40% of subjects will be enrolled in the United States.

PRIMARY ENDPOINT Target vessel failure (TVF), defined as cardiac death, target vessel myocardial infarction (MI) \[Q wave or non-Q wave, ARC-definition\], or clinically driven target vessel revascularization (TVR) by percutaneous or surgical methods within 270 days post-procedure.

SECONDARY ENDPOINTS

1. All Death at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days
2. Cardiac Death at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days
3. Major Adverse Cardiac Events (MACE), defined as cardiac death, MI (Q wave and non-Q wave), emergent bypass surgery, or clinically driven target lesion revascularization (TLR) by percutaneous or surgical methods at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days
4. MI at 30, 180 and 270, 360, 720, 1080, 1440, and 1800 days CeloNova Biosciences, Inc. Confidential CeloNova COBRA PzF™ Study Protocol # COBRA 2012-01 6 07 May 14
5. Clinically driven TLR at 30, 180, 270, 360, 720, 1080, 1440, and 1800 days
6. Stroke (ischemic and hemorrhagic) at 30, 180, 270 and 360 days
7. Clinically driven TVR at 30, 180, 270 and 360 days
8. Composite Endpoint of Cardiac Death and MI at 30, 180, 270, and 360 days
9. TVF at 30, 180, and 360 days
10. Acute Success Rates

    1. Device Success: Attainment of \< 30% final residual stenosis of the target lesion using only the COBRA PzFTM Coronary Stent System.
    2. Lesion Success: Attainment of \< 30% final residual stenosis of the target lesion using any percutaneous method.
    3. Procedure Success: Attainment of \< 30% final residual stenosis of the target lesion and no in-hospital MACE.
11. Bleeding or Vascular Complications at hospital discharge
12. Early Stent Thrombosis (ARC defined) at 30 days
13. Late Stent Thrombosis at 180, 270, and 360 days
14. Angiographic Endpoints (on first 90 evaluable patients) at 270 days (after clinical assessment)

    1. In-stent late loss (Secondary Endpoint hypothesis)
    2. In-segment percent diameter stenosis (%DS) (within the 5 mm margins proximal and distal to stent)
    3. In-stent percent diameter stenosis (%DS)
    4. In-segment late loss
    5. In-segment binary restenosis (stenosis of \> 50% of the reference vessel diameter)
    6. In-stent binary restenosis
    7. In-stent minimum lumen diameter (MLD)
    8. In-segment MLD
    9. Longitudinal stent deformation
    10. Stent fracture
15. Optical Coherence Tomography Endpoints (on 45 subjects) at 270 days (after clinical assessment)

    1. in-stent neointimal thickness (NT)
    2. Lumen area
    3. Lumen volume
    4. Stent area
    5. Stent volume
    6. Proportion of uncovered and/or malopposed struts
    7. Stent fracture

Eligibility criteria: General Inclusion Criteria:

1. Patient \>/= to 18 years old.
2. Eligible for percutaneous coronary intervention (PCI).
3. Patient understands the nature of the procedure and provides written informed consent prior to the catheterization procedure.
4. Patient is willing to comply with specified follow-up evaluation and can be contacted by telephone.
5. Acceptable candidate for coronary artery bypass graft (CABG) surgery.
6. Stable angina pectoris (Canadian Cardiovascular Society (CCS) 1, 2, 3 or 4) or unstable angina pectoris (Braunwald Class 1-3, B-C) or a positive functional ischemia study (e.g., ETT, SPECT, Stress echocardiography or Cardiac CT).
7. Male or non-pregnant female patient (Note: females of child bearing potential must have a negative pregnancy test prior to enrollment in the study).

Angiographic Inclusion Criteria

1. Patient indicated for elective stenting of a single stenotic lesion in a native coronary artery.
2. Reference vessel \>/= 2.5 mm and \</= 4.0 mm in diameter by visual estimate.
3. Target lesion \</= 24 mm in length by visual estimate (the intention should be to cover the whole lesion with one stent of adequate length).
4. Protected left main lesion with \>50% stenosis.
5. Target lesion stenosis \>/= 70% and \< 100% by visual estimate.
6. Target lesion stenosis \<70% who meet physiological criteria for revascularization (i.e. positive FFR).

General Exclusion Criteria:

1. Currently enrolled in another investigational device or drug trial that has not completed the primary endpoint or that clinically interferes with the current study endpoints.
2. Previously enrolled in another stent trial within the prior 2 years.
3. ANY planned elective surgery or percutaneous intervention within the subsequent 3 months.
4. A previous coronary interventional procedure of any kind within 30 days prior to the procedure.
5. The patient requires staged procedure of either the target or any non-target vessel within 9 months post-procedure.
6. The target lesion requires treatment with a device other than PTCA prior to stent placement (such as, but not limited to, directional coronary atherectomy, excimer laser, rotational atherectomy, etc.).
7. Previous drug eluting stent (DES) deployment anywhere in the target vessel.
8. Any previous stent placement within 15 mm (proximal or distal) of the target lesion.
9. Co-morbid condition(s) that could limit the patient's ability to participate in the trial or to comply with follow-up requirements, or impact the scientific integrity of the trial.
10. Concurrent medical condition with a life expectancy of less than 12 months.
11. Documented left ventricular ejection fraction (LVEF) \< 30% within 12 months prior to enrollment.
12. Patients with diagnosis of MI within 72 hours (i.e. CK-MB must be returned to normal prior to enrollment) or suspected acute MI at time of enrollment
13. Previous brachytherapy in the target vessel.
14. History of cerebrovascular accident or transient ischemic attack in the last 6 months.
15. Leukopenia (leukocytes \< 3.5 x 10(9) / liter).
16. Neutropenia (Absolute Neutrophil Count \< 1000/mm3) \</= 3 days prior to enrollment.
17. Thrombocytopenia (platelets \< 100,000/mm3) pre-procedure.
18. Active peptic ulcer or active GI bleeding.
19. History of bleeding diathesis or coagulopathy or inability to accept blood transfusions.
20. Known hypersensitivity or contraindication to aspirin, heparin or bivalirudin, clopidogrel or ticlopidine, cobalt, nickel, L-605 Cobalt chromium alloy or sensitivity to contrast media, which cannot be adequately pre-medicated.
21. Serum creatinine level \> 2.0 mg/dl within 7 days prior to index procedure.
22. Patients unable to tolerate dual anti-platelets therapy (DAPT) for one month post procedure.

Angiographic Exclusion Criteria

1. Unprotected left main coronary artery disease (obstruction greater than 50% in the left main coronary artery that is not protected by at least one non-obstructed bypass graft to the LAD or Circumflex artery or a branch thereof).
2. Target vessel with any lesions with greater than 50% diameter stenosis outside of a range of 5 mm proximal and distal to the target lesion based on visual estimate or on-line QCA.
3. Target lesion (or vessel) exhibiting an intraluminal thrombus (occupying \> 50% of the true lumen diameter) at any time.
4. Lesion location that is aorto-ostial or within 5 mm of the origin of the left anterior descending (LAD) or left circumflex (LCX).
5. Target lesion with side branches \> 2.0mm in diameter.
6. Target vessel is excessively tortuous (two bends \> 90˚ to reach the target lesion).
7. Target lesion is severely calcified.
8. TIMI flow 0 or 1
9. Target lesion is in a bypass graft

Primary outcomes:
measure: Target Vessel Failure (TVF)
timeFrame: 270 days
Secondary outcomes:
measure: All Cause Mortality
timeFrame: 30 days
measure: All Cause Mortality
timeFrame: 180 days
measure: All Cause Mortality
timeFrame: 270 days
measure: All Cause Mortality
timeFrame: 360 days
measure: All Cause Mortality
timeFrame: 1800 days
measure: Cardiac Mortality
timeFrame: 30 days
measure: Cardiac Mortality
timeFrame: 180 days
measure: Cardiac Mortality
timeFrame: 270 days
measure: Cardiac Mortality
timeFrame: 360 days
measure: Cardiac Mortality
timeFrame: 1800 days
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 30 days
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 180 days
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 270 days
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 360 days
measure: Major Adverse Cardiac Events (MACE)
timeFrame: 1800 days
measure: Myocardial Infarction (MI-ARC Definition)
timeFrame: 30 days
measure: Myocardial Infarction (MI-ARC Definition)
timeFrame: 180 days
measure: Myocardial Infarction (MI-ARC Definition)
timeFrame: 270 days
measure: Myocardial Infarction (MI-ARC Definition)
timeFrame: 360 days
measure: Myocardial Infarction (MI-ARC Definition)
timeFrame: 1800 days
measure: Cardiac Death or MI (ARC Definition)
timeFrame: 30 days
measure: Cardiac Death or MI (ARC Definition)
timeFrame: 180 days
measure: Cardiac Death or MI (ARC Definition)
timeFrame: 270 days
measure: Cardiac Death or MI (ARC Definition)
timeFrame: 360 days
measure: Clinically Driven TLR
timeFrame: 30 days
measure: Clinically Driven TLR
timeFrame: 180 days
measure: Clinically Driven TLR
timeFrame: 270 days
measure: Clinically Driven TLR (Clinical and Angiographic Cohorts)
timeFrame: 360 days
measure: Clinically Driven TLR (Clinical Cohorts)
timeFrame: 360 days
measure: Clinically Driven TLR (Clinical and Angiographic Cohorts)
timeFrame: 1800 days
measure: Clinically Driven TLR (Clinical Cohorts)
timeFrame: 1800 days
measure: Clinically Driven TVR
timeFrame: 30 days
measure: Clinically Driven TVR
timeFrame: 180 days
measure: Clinically Driven TVR
timeFrame: 270 days
measure: Clinically Driven TVR
timeFrame: 360 days
measure: Target Vessel Failure (TVF)
timeFrame: 30 days
measure: Target Vessel Failure (TVF)
timeFrame: 180 days
measure: Target Vessel Failure (TVF)
timeFrame: 360 days
measure: Stroke (Ischemic and Hemorrhagic)
timeFrame: 30 days
measure: Stroke (Ischemic and Hemorrhagic)
timeFrame: 180 days
measure: Stroke (Ischemic and Hemorrhagic)
timeFrame: 270 days
measure: Device Success
timeFrame: 30 days
measure: Stroke (Ischemic and Hemorrhagic)
timeFrame: 360 days
measure: Lesion Success
timeFrame: 30 days
measure: Procedure Success
timeFrame: 30 days
measure: Bleeding or Vascular Complications
timeFrame: 30 days
measure: Early Stent Thrombosis (ARC Definition)
timeFrame: 30 days
measure: Late Stent Thrombosis
timeFrame: 180 days
measure: Late Stent Thrombosis
timeFrame: 270 days
measure: Late Stent Thrombosis
timeFrame: 360 days
measure: Definite and Probable Stent Thrombosis
timeFrame: 1800 days
measure: In-Segment Percent Diameter Stenosis
timeFrame: 270 days
measure: In-Stent and In-Segment MLD and Late Loss
timeFrame: 270 days
measure: Angiographic Endpoints
timeFrame: 270 days
measure: In-stent Neointimal Thickness (INT)
timeFrame: 270 days
measure: Percentage of Uncovered and/or Malapposed Struts
timeFrame: 270 days
measure: Lumen and Stent Area Measurements
timeFrame: 270 days
measure: Lumen and Stent Volume
timeFrame: 270 days
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Bakersfield Memorial Hospital
state: California
city: Miami Beach
country: United States
facility: Mt Sinai Medical Center
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Heart Center of Indiana
state: Indiana
city: Lacombe
country: United States
facility: Louisiana Heart Hospital
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Browns Mills
country: United States
facility: Deborah Heart & Lung Center
state: New Jersey
city: Liverpool
country: United States
facility: St Joseph's Hospital
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: Oklahoma City
country: United States
facility: Oklahoma Foundation for Cardiovascular Research
state: Oklahoma
city: Medford
country: United States
facility: Southern Oregon Cardiology
state: Oregon
city: York
country: United States
facility: York General Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Cardiology Consultants of Texas
state: Texas
city: Fort Worth
country: United States
facility: Plaza Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Hospital
state: Texas
city: Lubbock
country: United States
facility: Texas Cardiac Center
state: Texas
city: Plano
country: United States
facility: The Heart Hospital Baylor Plano
state: Texas
city: San Antonio
country: United States
facility: San Antonio Endovascular & Heart Institute
state: Texas
city: Tyler
country: United States
facility: Tyler Cardiovascular Consultants
state: Texas
city: Richmond
country: United States
facility: Virginia Cardiovascular Specialists
state: Virginia
city: Wausau
country: United States
facility: Aspirus Heart & Vascular Institute
state: Wisconsin
city: Aix en Provence
country: France
facility: Clinique Axium
city: Avignon
country: France
facility: Hopital Henri Duffaut
city: Colmar
country: France
facility: Albert Schweitzer Hospital
city: Mulhouse
country: France
facility: Clinique du Diaconat
city: Pau
country: France
facility: Centre Hospitalier de Pau
city: Rouen
country: France
facility: Clinique St. Hilaire
city: Frankfurt
country: Germany
facility: Sankt Kathatinen Hospital
city: Munchen
country: Germany
facility: Kardiologische Praxis und Praxisklinik
city: Riga
country: Latvia
facility: Paul Stradins Clinical University Hospital
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
Study officials:
affiliation: Executive Director, Clinical Investigation, Harvard Clinical Research Institute
name: Donald Cutlip, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Professor of Medicine at The University of Munich
name: Sigmund Sliber, MD
role: PRINCIPAL_INVESTIGATOR
References: