Study of Vascular Healing With the Combo Stent Versus the Everolimus Eluting Stent in ACS Patients by Means of OCT (REMEDEE-OCT)
|ClinicalTrials.gov Identifier: NCT01405287|
Recruitment Status : Completed
First Posted : July 29, 2011
Last Update Posted : March 24, 2014
OBJECTIVE It is the objective of the REMEDEE OCT study to assess vascular healing after deployment of the Abluminal Sirolimus Coated Bio-Engineered Stent (Combo Bio-Engineered Sirolimus Eluting Stent) in patients with Acute Coronary Syndrome (ACS) with single de novo native coronary artery lesions ranging in diameter from ≥2.5 mm to ≤3.5 mm and ≤ 20 mm in length.
STUDY DESIGN The REMEDEE OCT study is a prospective, multicenter, randomized study designed to enroll 60 patients with ACS who will be randomized 1:1 to be treated with the Combo stent versus the commercially available everolimus eluting stent (Xience V or Promus). Patients will receive Optical Coherence Tomography (OCT) and Quatitative Coronary Angiography (QCA) follow-up imaging at 60 days post procedure. Clinical follow-up is scheduled at 30, 60, 180, 360 and 540 days. Furthermore, QCA and OCT will also be performed at baseline in all participants of the study.
|Condition or disease||Intervention/treatment||Phase|
|Coronary Artery Disease Atherosclerosis Acute Coronary Syndrome (ACS) Myocardial Infarction (MI)||Device: PTCA with stent placement||Phase 2|
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BACKGROUND The implantation of bare-metal stents (BMS) has significantly reduced clinical and angiographic restenosis compared to balloon angioplasty alone after PCI due to eliminating elastic recoil and reducing arterial remodeling. However, in-stent restenosis still occurred frequently after BMS implantation in 20% to 40% of patients due to neointimal proliferation. The development, clinical validation and widespread use of drug-eluting stents (DES) have revolutionized the treatment of patients with coronary artery disease. Large-scale, prospective, multicenter double-blind randomized trials have provided strong evidence that drug-eluting stents significantly reduce angiographic restenosis and enhance event-free survival compared with BMS after implantation in native coronary arteries (3-6).However, despite an improved efficacy in the prevention of restenosis and target vessel failure safety concerns have been raised for DES, focusing on a small but clinically important increase in stent thrombosis occurring greater than one year after the index procedure.
In patients receiving drug-eluting stents, the acute coronary syndrome has been identified as one of the major risk factors of stent thrombosis (10). Therefore, concerns about the long-term outcome and safety after drug-eluting stent implantation due to late stent thrombosis and late stent malapposition have been raised.
Stent thrombosis, in particular late stent thrombosis, has been related to an impaired stent healing, most of all to a reduced endothelial repair, i.e. reduced stent strut coverage, after implantation of drug-eluting stents. This has resulted in the recommendation of a prolonged 12-month double antiplatelet therapy with aspirin and clopidogrel after drug-eluting stent implantation, however, how long double antiplatelet therapy is needed is unknown at present. These observations have resulted in an intense search for alternative strategies to promote stent healing and endothelial repair, rather than to inhibit the endothelialisation of the stent, that is common to the substances used to prevent neointima formation.
Notably, endothelial repair can be substantially stimulated by CD34+ endothelial progenitor cells. The Combo stent is therefore covered with a CD34+ antibody to attract endothelial progenitor cells to promote endothelial and stent healing, and on the abluminal side releases sirolimus to prevent neointima formation and restenosis. Several preclinical studies in the porcine coronary artery model have shown, that endothelialisation and stent healing are accelerated in the Combo stent. The present study has therefore been designed to compare stent healing of the Combo stent with the everolimus-eluting stent by optical coherence tomography analysis (optical frequency domain imaging; OFDI), a high resolution intracoronary imaging technique allowing accurate evaluation of stent coverage and healing, in patients with an acute coronary syndrome. Previous studies have indicated, that coronary stent healing after DES implantation is particularly impaired in patients with ACS, and therefore this patient population is in a particular need of improved "pro-healing" stent concepts with a high efficacy.
RATIONALE An important limitation of stents eluting only growth-inhibiting substances is, that also the desirable endothelial cell growth over the stent struts is prevented, that is thought to represent a major cause of "late-stent-thrombosis". The rationale for the design of the "combo-stent" is therefore to combine a growth inhibiting substance with abluminal release with an endothelial progenitor cell attracting design to promote endothelial repair. In the pre-clinical studies, the "Combo Stent" demonstrated significantly lower neointimal hyperplasia, while also showing improved endothelial coverage relative to other commercially available DES. There was also a noticeably lower presence of inflammation and foreign body reaction.
OCT- Examination of Vessel Healing Optical coherence tomography (OCT) is a novel intravascular imaging modality based on infrared light emission that has a 10-20 fold higher resolution (10-20 µM) as compared to current intravascular ultrasound systems, and allows a detailed examination of stent healing. Strut coverage, strut apposition and neointima can be quantified at a micron-scale level with a resolution 10-20 times higher than conventional intravascular ultrasound. The quantification of stent healing by intravascular OCT analysis has recently been validated against histology, demonstrating an excellent accuracy of the OCT examination. Moreover, the safety and feasibility of OCT examination in a multicenter study has been demonstrated. Newer modalities of OCT image acquisition, as used in this study, have been reported to further simplify the technique and reduce procedural time.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||A Prospective Randomized Study to Compare Vascular Healing After Deployment of the Abluminal Sirolimus Coated Bio-Engineered (Combo) Stent Versus the Everolimus Eluting Stent in Patients With Acute Coronary Syndrome by Means of OCT|
|Study Start Date :||October 2011|
|Actual Primary Completion Date :||August 2012|
|Actual Study Completion Date :||January 2014|
Experimental: Combo Stent
PTCA with Combo Stent
Device: PTCA with stent placement
PTCA with stent placement (Drug Eluting Stent)
Active Comparator: Everolimus Eluting Stent (EES)
PTCA with DES (Everolimus Eluting Stent: Xience V or Promus)
Device: PTCA with stent placement
PTCA with stent placement (Drug Eluting Stent)
- Percentage of uncovered stent struts per stent at follow-up (OCT) [ Time Frame: 60 days ]
- Secondary Clinical Endpoint: Major Adverse Cardiac Events (MACE) [ Time Frame: 30, 60, 180, 360, 540 days ]Major Adverse Cardiac Events (MACE)defined as a composite of death, Myocardial Infarction (MI) (Q wave or non-Q wave), emergent coronary artery bypass surgery (CABG), or justified target lesion revascularization (TLR) by repeat Percutaneous Transluminal Coronary Angioplasty (PTCA) or Coronary Artery Bypass Grafting (CABG) at hospital discharge
- Secondary Clinical Endpoint: components of MACE: cardiac death [ Time Frame: 30, 60, 180, 360, 540 days ]cardiac death
- Secondary Clinical Endpoints: components of MACE: MI [ Time Frame: 30, 60, 180, 360, 540 days ]MI (Q wave or non-Q wave)
- Secondary Clinical Endpoints: components of MACE: CABG or re-PTCA of target lesion [ Time Frame: 30, 60, 180, 360, 540 days ]emergent coronary artery bypass surgery (CABG), or clinically justified target lesion revascularization (TLR) by repeat PTCA or CABG at hospital discharge
- Secondary Clinical Endpoints: Stent thrombosis [ Time Frame: 30, 60, 180, 360, 540 days ]Target vessel stent thrombosis per Academic Research Consortium (ARC) definition
- Secondary OCT Endpoints (1/12) [ Time Frame: 60 days ]Percentage of stent strut malapposition
- Secondary OCT Endpoints (2/12) [ Time Frame: 60 days ]Maximum length of segments (mm) with uncovered struts
- Secondary OCT Endpoints (3/12) [ Time Frame: 60 days ]Maximum length of segments (mm) with malapposed struts
- Secondary OCT Endpoints (4/12) [ Time Frame: 60 days ]Maximum malapposition distance (mm)
- Secondary OCT Endpoints (5/12) [ Time Frame: 60 days ]Total malapposition volume
- Secondary OCT Endpoints (6/12) [ Time Frame: 60 days ]Maximal malapposition volume
- Secondary OCT Endpoints (7/12) [ Time Frame: 60 days ]Mean neointimal thickness (NIT)(strut level)
- Secondary OCT Endpoints (8/12) [ Time Frame: 60 days ]Percentage of protruding struts per stent
- Secondary OCT Endpoints (9/12) [ Time Frame: 60 days ]Frequency of Abnormal Intrastent Tissue (AIST)
- Secondary OCT Endpoints (10/12) [ Time Frame: 60 days ]Stent Volume
- Secondary OCT Endpoints (11/12) [ Time Frame: 60 days ]Lumen Volume
- Secondary OCT Endpoints (12/12) [ Time Frame: 60 days ]Neointimal Hyperplasia (NIH) Volume
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01405287
|OLV Ziekenhuis Aalst|
|Aalst, Belgium, 9300|
|Antwerp, Belgium, 2020|
|Satakunta Central Hospital|
|Pori, Finland, 28500|
|Academisch Medisch Centrum|
|Amsterdam, Netherlands, 1105 AZ|
|University Hospital Zurich|
|Zurich, Switzerland, 8032|
|King's College Hospital|
|London, United Kingdom, SE5 9RS|
|Principal Investigator:||Ulf Landmesser, MD, PhD||University of Zurich|