Study of Vascular Healing With the Combo Stent Versus the Everolimus Eluting Stent in ACS Patients by Means of OCT
Condition: Coronary Artery Disease; Atherosclerosis; Acute Coronary Syndrome (ACS); Myocardial Infarction (MI)
MeSH terms: Coronary Artery Disease; Myocardial Infarction; Acute Coronary Syndrome; Atherosclerosis; Syndrome; Infarction
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): PTCA with stent placement
Intervention type(s): Device
Intervention description(s): PTCA with stent placement (Drug Eluting Stent)
Other intervention name(s): Combo Stent; Xience V or Promus stent
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: stent; drug eluting stent; healing; endothelium; DES; OCT; MI; ACS