Clinical trial NCT00967902: Safety and Effectiveness Study of Combo Bio-engineered Sirolimus Eluting Stent
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Coronary Artery Lesions
Keywords: intracoronary stent
drug eluting stent
sirolimus
endothelial progenitor cells
Lead sponsor: OrbusNeich
Sponsor class: INDUSTRY
First posted: 2009-08-28
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: In-stent late lumen loss of the Combo Stent compared to the TAXUS® Liberté® DES
timeFrame: 9 months post-procedure.
Secondary outcomes:
measure: All-cause and cardiac mortality
timeFrame: 30 days, 9 months, 1, 2, 3, 4, and 5 year
measure: Myocardial infarction: Q-wave and non Q-wave, cumulative and individual
timeFrame: 30 days, 9 months, 1, 2, 3, 4, and 5 years
measure: 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
timeFrame: Hospital discharge, 30 days, 9 months, 1, 2, 3, 4 and 5 years post-procedure
measure: Vascular complications from index procedure
timeFrame: Up to hospital discharge
measure: Rate of stent thrombosis, per ARC definition of definite and probable stent thrombosis further categorized as early, late or very late
timeFrame: 30 days, 9 months, 1, 2, 3, 4 and 5 years post-procedure
measure: Change in human anti-murine antibody (HAMA) plasma levels
timeFrame: 30 day and 9 month follow-up compared to baseline
measure: Device success, defined as attainment of <50% residual stenosis of the target lesion using the Combo Stent
timeFrame: Index procedure
measure: Lesion success defined as attainment of < 50% residual stenosis using any percutaneous method
timeFrame: Index procedure
measure: Procedure success defined as lesion success without the occurrence of in-hospital MACE
timeFrame: Up to hospital discharge
measure: Clinically (ischemia)-driven target lesion revascularization
timeFrame: 30 days, 9 months, 1, 2, 3, 4 and 5 years
measure: Clinically (ischemia)-driven target vessel revascularization
timeFrame: 30 days, 9 months, 1, 2, 3, 4 and 5 years
measure: In-stent and in-segment angiographic binary restenosis
timeFrame: 9 months
measure: In-stent and in-segment minimum lumen diameter (MLD)
timeFrame: 9 months
measure: In-stent, proximal and distal late lumen loss
timeFrame: 9 months
measure: Neointimal hyperplasia volume and % in-stent volume obstruction as measured by intravascular ultrasound (IVUS) for patients receiving angiographic/IVUS follow-up
timeFrame: 9 months
measure: Target lesion failure (TLF) (defined as death, MI and ischemic target lesion revascularization (TLR))
timeFrame: 30 days, 9 months, 1, 2, 3, 4 and 5 years
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: John Hunter Hospital
state: New South Wales
Study officials:
affiliation: Monash University
name: Ian T Meredith, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Bern
name: Stephan Windecker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Inst Dante Pazzanese of Cardiology
name: Alexandre Abizaid, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CardioVascular Research Foundation
name: Roxana Mehran, MD
role: STUDY_DIRECTOR
affiliation: CardioVascular Research Foundation
name: Alexandra Lansky, MD
role: STUDY_DIRECTOR
References:
citation: 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.