The GENOUS Stent (the EPC Capturing R-stent, OrbusNeich Medical Inc., Fort Lauderdale, FL) is
commercially available and has been extensively used in standard coronary intervention
procedures treating >200 patients with critical coronary stenoses at Queen Mary Hospital. The
COMBO Stent (OrbusNeich Medical Inc., Fort Lauderdale, FL) is a hybrid version of the GENOUS
Stent with an abluminal sirolimus coating, and is currently under the investigational use for
clinical research in the REMEDEE Study; over 20 patients have been treated and all remained
in good condition since the treatment.
The GENOUS Stent is a bio-engineered 316L stainless steel coronary stent with a biocompatible
circumferential coating of anti-CD34 antibody, and will bind to and therefore capture the
circulatory endothelial progenitor cells (EPC) which have CD34 antigen on the surface.
Immobilization of EPCs on the stent surface will encourage differentiation and proliferation
of the EPCs into endothelial and neointimal layer. Animal model has demonstrated that a
functional endothelial layer could be formed as soon as 24 to 48 hours after GENOUS stent
implantation (1). The HEALING-FIM registry has shown that GENOUS stent is clinically safe and
effective in the treatment of coronary stenosis (2). Recent reports have further confirmed
its efficacy in patients with acute coronary syndrome requiring urgent revascularization
(3,4).
The COMBO Stent is a hybrid version of the GENOUS Stent, with an additional abluminal, drug
eluting sirolimus coating, targeted to reduce excessive neointima formation, while
maintaining the EPC capturing capacity and therefore continue to promote healing after stent
injury. The hybrid function of these two technologies in this new COMBO stent is expected to
produce better clinical results in terms of accelerated healing, less stent thrombosis and
less restenosis; these are being investigated in the current REMEDEE Study.
Animal study has shown the COMBO Stent promotes endothelialization and reduces neointima
formation, as assessed by both optical coherence tomography (OCT) and histopathology (5).
Even though COMBO Stents have been used and found to be safe in over 180 patients world-wide
and in about 30 patients at Queen Mary Hospital under the REMEDEE Study Protocol, such
benefits of "early" endothelial coverage as assessed by OCT has never been fully documented
in human subjects.
The current EGO-COMBO study protocol is designed based on the approved protocols of the
ongoing REMEDEE Study (IRB: UW 09-384) and the EGO Study (IRB: UW 10-256); both are still
active in this Hospital. In the multi-center REMEDEE Study, the COMBO stent is compared to
the TAXUS stent (Boston Scientific) in patients with coronary artery disease requiring stent
implantation, looking at the 9 months late loss results. This EGO-COMBO Study is different
from the REMEDEE Study and focuses mainly on the very early time frames assessing the degree
of early neointimal healing (enhanced endothelialization) between 2nd to 5th months, and the
subsequent neointimal proliferation at 9 months after the COMBO Stent implantation, as
assessed by the very high resolution of the frequency domain optical coherence tomography
(OCT) used in the existing EGO study. This is a single centre, non-randomized, open-label
study.
Intracoronary frequency domain optical coherence tomography (FD-OCT) is a simple
catheter-based imaging technique using optic fibre to achieve very detailed assessment
(resolution down to 10 microns) of the stents, in terms of stent apposition, early neointimal
coverage (enhanced endothelialization) and late stent neointimal growth (restenosis). It is
performed as part of the routine cardiac catheterization procedure and provides
high-resolution cross sectional images of the coronary arteries. OCT has been shown to be
safe in clinical practice (6, 7). The LightLab C7XR OCT System (Frequency Domain OCT) is a
commercially available product with CE Mark and FDA approval, and is being used in our EGO
Study. The Dragonfly OCT catheter used is a non-occlusive optic fibre which is extremely
small and flexible, and will pose absolutely no additional risk to the patient under
treatment, other than those inherent risks of a standard angioplasty procedure.
In this prospective, pilot study, OCT is used to image the COMBO Stent after implantation to
evaluate both the early healing (stent apposition, neointimal coverage) and late lumen loss
(neo-intimal thickness and neo-intimal area). Clinical outcomes will also be monitored as
secondary end points. The OCT analyses will be performed by an USA based core laboratory,
which is blinded from the time frame of the OCT pullbacks and the clinical details.
