Safety and Effectiveness Study of Combo Bio-engineered Sirolimus Eluting Stent

Study Overview
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Brief Summary
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To demonstrate the safety and effectiveness of the Combo Bio-engineered Sirolimus Eluting Stent (Combo Stent) compared to the Taxus® Liberté® Stent in the treatment of coronary artery lesions.

Official Title
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The REMEDEE Study: A Prospective, Randomized Study to Evaluate the Safety and Efficacy of an Abluminal Sirolimus Coated Bio-engineered Stent (Combo Bio-engineered Sirolimus Eluting Stent)

Conditions
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Coronary Artery Lesions

Intervention / Treatment
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* Device: coronary stenting


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: General Inclusion Criteria The patient must be ≥18 and ≤ 80 years of age; Symptomatic ischemic heart disease (CCS class 1-4, Braunwald Class IB, IC, IIB, IIC, IIIB, IIIC, and/or objective evidence of myocardial ischemia); Acceptable candidate for CABG; The Patient is willing to comply with specified follow-up evaluations; The Patient or legally authorized representative has been informed of the nature of the study, agrees to its provisions and has been provided written informed consent, approved by the appropriate Medical Ethics Committee (MEC), Institutional Review Board (IRB), or Human Research Ethics Committee (HREC). Angiographic Inclusion Criteria: Single de novo or non-stented restenotic lesion in the target vessel; Patients with two-vessel coronary disease, may have undergone successful treatment (<20% diameter stenosis by visual estimate) of the non-target vessel with approved devices up to and including the index procedure but must be prior to the index target vessel treatment. Any non-target vessel or lesion intended to be treated during the index procedure, cannot be an unprotected left main, ostial lesion, chronic total occlusion (CTO), heavily calcified, bifurcation, vein grafts, have angiographic evidence of thrombus, be anything requiring atherectomy, thrombectomy, or pre-treatment with anything other than balloon angioplasty; Target lesion located in a native coronary artery; Target lesion (maximum length is 20 mm by visual estimate) covered by a single stent maximum 23 mm length for Combo Stent, and 24 mm in length for TAXUS® Liberté® (stent coverage including at least 3 mm of healthy vessel is recommended). The lesion length should be measured after pre-dilation procedure; Reference vessel diameter must be ≥2.5 to ≤ 3.5 mm by visual estimate. The vessel diameter should be measured after pre-dilation procedure and after intra-coronary nitroglycerin if spasm is suspected; Target lesion ≥50% and <100% stenosed by visual estimate. Exclusion Criteria: General Exclusion Criteria: Pregnant or nursing patients and those who plan pregnancy in the period up to 1 year following index procedure. Female patients of child-bearing potential must have a negative pregnancy test done within 7 days prior to the index procedure per site standard test; Patient has had a known diagnosis of acute myocardial infarction (AMI) within 72 hours preceding the index procedure (elevated troponin or CK-MB ≥2 times upper limit of normal) or >72 hours preceding the index procedure and CK and CK-MB have not returned to within normal limits at the time of procedure; The patient is currently experiencing clinical symptoms consistent with new onset AMI, such as nitrate unresponsive prolonged chest pain; Impaired renal function (serum creatinine >2.0 mg/dL or 177 μmol/l) or on dialysis; Platelet count <100,000 cells/mm3 or >700,000 cells/mm3 or a WBC <3,000 cells/mm3; Patient has a history of bleeding diathesis or coagulopathy or patients in whom anti-platelet and/or anticoagulant therapy is contraindicated; Patient requires low molecular weight heparin (LMWH) treatment post-procedure or has received a dose of LMWH ≤8 hours prior to index procedure; Patient has received any organ transplant or is on a waiting list for any organ transplant; Patient has other medical illness (e.g., cancer, known malignancy, or congestive heart failure) or known history of substance abuse (alcohol, cocaine, heroin etc.) that may cause non-compliance with the protocol, confound the data interpretation or is associated with a limited life expectancy (i.e., less than 1 year); Patient has a known hypersensitivity or contraindication to aspirin, heparin/bivalirudin, clopidogrel/ticlopidine, prasugrel, stainless steel alloy, sirolimus, paclitaxel and/or contrast sensitivity that cannot be adequately pre-medicated; Patient has previously received murine therapeutic antibodies and exhibited sensitization through the production of Human Anti-Murine Antibodies (HAMA); Patient presents with cardiogenic shock; Patient has current unstable cardiac arrhythmias that create hemodynamic instability; Patient has extensive peripheral vascular disease that precludes safe 6 French sheath insertion; Any significant medical condition which in the Investigator's opinion may interfere with the patient's optimal participation in the study; Currently participating in another investigational drug or device study or patient in inclusion in another investigational drug or device study during follow-up; Angiographic Exclusion Criteria: Unprotected left main coronary artery disease with ≥50% stenosis; Ostial target lesion(s); Totally occluded target vessel (TIMI flow 0); Calcified target lesion(s) which cannot be successfully predilated; Target lesion has excessive tortuosity unsuitable for stent delivery and deployment; Angiographic evidence of thrombus in the target lesion(s); Target lesion involving bifurcation with a side branch ≥2.0 mm in diameter (either stenosis of both main vessel and major side branch or stenosis of just major side branch) that would require intervention of diseased side branch; A significant (>50%) stenosis proximal or distal to the target lesion that cannot be covered by same single stent; Diffuse distal disease to target lesion with impaired runoff; Left ventricular ejection fraction (LVEF) ≤30% (LVEF must be obtained within 6 months prior to the index procedure); Pre-treatment with devices other than balloon angioplasty; Prior stent within 10 mm of target lesion; Intervention (PCI or bypass) of another lesion performed within 6 months before or planned within 30 days following the index procedure.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combo<br>The Combo Stent is composed of the OrbusNeich R stent™, with an abluminal coating of a bioabsorbable polymer matrix formulated with sirolimus for sustained release, and an anti-CD34 antibody cell capture coating on the luminal surface. | Device: coronary stenting<br>* Balloon dilatation of obstructive coronary artery disease with deployment of a metallic stent to scaffold the dilated lesion; stent incorporating sustained release of anti-proliferative agent to control neointimal proliferation and reocclusion; test device incorporates affinity surface for circulating EPCs<br>|
| Active Comparator: Taxus® Liberté® Stent<br>Commercially available product | Device: coronary stenting<br>* Balloon dilatation of obstructive coronary artery disease with deployment of a metallic stent to scaffold the dilated lesion; stent incorporating sustained release of anti-proliferative agent to control neointimal proliferation and reocclusion; test device incorporates affinity surface for circulating EPCs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| In-stent late lumen loss of the Combo Stent compared to the TAXUS® Liberté® DES |  | 9 months post-procedure. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause and cardiac mortality |  | 30 days, 9 months, 1, 2, 3, 4, and 5 year | 
| Myocardial infarction: Q-wave and non Q-wave, cumulative and individual |  | 30 days, 9 months, 1, 2, 3, 4, and 5 years | 
| Major Adverse Cardiac Event (MACE) defined as a composite of death, MI (Q-wave or non Q-wave), emergent CABG, or target lesion revascularization by repeat PTCA or CABG |  | Hospital discharge, 30 days, 9 months, 1, 2, 3, 4 and 5 years post-procedure | 
| Vascular complications from index procedure |  | Up to hospital discharge | 
| Rate of stent thrombosis, per ARC definition of definite and probable stent thrombosis further categorized as early, late or very late |  | 30 days, 9 months, 1, 2, 3, 4 and 5 years post-procedure | 
| Change in human anti-murine antibody (HAMA) plasma levels |  | 30 day and 9 month follow-up compared to baseline | 
| Device success, defined as attainment of <50% residual stenosis of the target lesion using the Combo Stent |  | Index procedure | 
| Lesion success defined as attainment of < 50% residual stenosis using any percutaneous method |  | Index procedure | 
| Procedure success defined as lesion success without the occurrence of in-hospital MACE |  | Up to hospital discharge | 
| Clinically (ischemia)-driven target lesion revascularization |  | 30 days, 9 months, 1, 2, 3, 4 and 5 years | 
| Clinically (ischemia)-driven target vessel revascularization |  | 30 days, 9 months, 1, 2, 3, 4 and 5 years | 
| In-stent and in-segment angiographic binary restenosis |  | 9 months | 
| In-stent and in-segment minimum lumen diameter (MLD) |  | 9 months | 
| In-stent, proximal and distal late lumen loss |  | 9 months | 
| Neointimal hyperplasia volume and % in-stent volume obstruction as measured by intravascular ultrasound (IVUS) for patients receiving angiographic/IVUS follow-up |  | 9 months | 
| Target lesion failure (TLF) (defined as death, MI and ischemic target lesion revascularization (TLR)) |  | 30 days, 9 months, 1, 2, 3, 4 and 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intracoronary stent, drug eluting stent, sirolimus, endothelial progenitor cells