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

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)

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.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Lesions
• Intervention / Treatment: Device: coronary stenting

• Study Type: Interventional
• Enrollment (Actual): 180
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2300
      • John Hunter Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combo; 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; 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
Active Comparator: Taxus® Liberté® Stent; Commercially available product	Device: coronary stenting; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: OrbusNeich
• Investigators: Principal Investigator: Ian T Meredith, MBBS, PhD, Monash University; Principal Investigator: Stephan Windecker, MD, University of Bern; Principal Investigator: Alexandre Abizaid, MD, Inst Dante Pazzanese of Cardiology; Study Director: Roxana Mehran, MD, CardioVascular Research Foundation; Study Director: Alexandra Lansky, MD, CardioVascular Research Foundation

Publications and helpful links

General Publications

• Haude M, Lee SW, Worthley SG, Silber S, Verheye S, Erbs S, Rosli MA, Botelho R, Meredith I, Sim KH, Stella PR, Tan HC, Whitbourn R, Thambar S, Abizaid A, Koh TH, Den Heijer P, Parise H, Cristea E, Maehara A, Mehran R. The REMEDEE trial: a randomized comparison of a combination sirolimus-eluting endothelial progenitor cell capture stent with a paclitaxel-eluting stent. JACC Cardiovasc Interv. 2013 Apr;6(4):334-43. doi: 10.1016/j.jcin.2012.10.018. Epub 2013 Mar 20.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: August 26, 2009
• First Submitted That Met QC Criteria: August 27, 2009
• First Posted (Estimate): August 28, 2009

Study Record Updates

• Last Update Posted (Estimate): March 29, 2016
• Last Update Submitted That Met QC Criteria: March 28, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: drug eluting stent; sirolimus; endothelial progenitor cells; intracoronary stent
• Other Study ID Numbers: VP-0427