Evaluation of HealinG of Polymer-Free Biomlimus A9-Coated Stent by Optical Coherence Tomography (EGO-BIOFREEDOM)
Condition: Coronary Disease
MeSH terms: Coronary Disease
Study type: Interventional

Summary: 
      Since polymers have been identified as a possible cause of late complications of drug eluting
      stents, new stents are being designed to improve polymers' biocompatibility or to bond drugs
      on stents without polymers.

      Biolimus A9 is the therapeutic agent used in the BioFreedom drug coated stent. Biolimus A9 is
      a proprietary semi-synthetic sirolimus derivative. It is highly lipophilic, rapidly absorbed
      in tissues, and able to reversibly inhibit growth factor-stimulated cell proliferation.

      In this study, we use intracoronary optical coherence tomography (OCT) to evaluate the
      BioFreedom Stents after implantation regarding endovascular healing over time as primary
      objective; and also to evaluate secondary OCT, angiographic and clinical outcomes at various
      specific time points.
    

Detailed description: 
      Intra-coronary stenting is currently the standard of care post-balloon angioplasty for
      ischemic heart disease. Traditionally, bare metal stent (BMS) is used but in recent years it
      has been largely been replaced by drug-eluting stent (DES) which has reduced rates of
      restenosis. (1) However, the long term safety of DES still remains controversial due to
      reports of late stent thrombosis which presumably occurs secondary to delayed arterial
      healing and local hypersensitivity reactions which may be related to the drug, the polymer,
      or both. (2). Virmani et al (3) reported that patients who died of late stent thrombosis 18
      months after sirolimus-eluting stent (SES) implantation showed a severe localized
      hypersensitivity reaction that involved the whole vessel wall and this reaction may be caused
      by polymer or from the drug-release kinetics of SES. It is known from preclinical and
      clinical studies that, nonabsorbable polymer can induce persistent inflammation which may
      lead to delayed cellular proliferation and 'late catch-up' restenosis (4).

      Early (ie first) generation DES consisted of a metal stent for vessel scaffolding, cytotoxic
      drug for neointimal growth inhibition and a polymer coating to improve the biocompatibility
      of the stents or as a vehicle to load drugs onto stents. Since polymers have been identified
      as a possible cause of late complications of DES, new stents are being designed to improve
      polymers' biocompatibility or to bond drugs on stents without polymers. Biodegradable
      polymers are likely to be safer than nonabsorbable polymers because inflammation will be
      eliminated after the polymer degrades.

      The BioFreedom drug coated stent (DCS) Coronary Stent Delivery System is comprised of three
      key components including 1) a 316 L stainless steel bare metal stent platform which has been
      modified with a proprietary surface treatment resulting in a selectively micro-structured,
      abluminal surface. The selectively micro-structured surface allows 2) Biolimus A9TM (drug)
      adhesion to the abluminal surface of the stent without the use of a polymer or binder. The
      drug-coated stent is crimped onto 3) a delivery system which includes a high pressure,
      semi-compliant balloon incorporated onto the distal tip of a rapid exchange delivery catheter
      system. The delivery system has two radiopaque markers inside the balloon, which
      fluoroscopically mark the ends of the stent to facilitate proper stent placement.

      Biolimus A9 is the therapeutic agent used in the BioFreedom DCS. Biolimus A9 is a proprietary
      semi-synthetic sirolimus derivative. It is highly lipophilic, rapidly absorbed in tissues,
      and able to reversibly inhibit growth factor-stimulated cell proliferation. Current data
      suggest that Biolimus A9, on a molecular level, forms a complex with the cytoplasmic proteins
      that inhibit the cell cycle between the G0 and G1 phase. The result is an interruption of the
      cascade governing cell reproduction, growth, and proliferation. Related pharmaceuticals,
      sirolimus and everolimus, are well tolerated cytostatic immunosuppressive agents with
      predictable and similar adverse event profiles. Biolimus A9 is closely related chemically to
      both sirolimus and everolimus. Based on administration in healthy volunteers, Biolimus A9 has
      been shown to have a very similar adverse event profile to these other two drugs when used at
      equivalent dose levels., Biolimus A9 easily crosses the cell membrane to achieve therapeutic
      effects in target smooth muscle cells and, compared with the sirolimus-eluting Cypher stent
      (SES), the high lipophilicity of BA9 leads to relatively low systemic exposure.(5)
      Furthermore, the drug coating is applied only to the abluminal surface of the stent, allowing
      the drug release to be directed almost entirely into the vessel wall where it targets the
      smooth muscle cells injured by the angioplasty procedure. On the other hand, there is little
      drug release on the luminal surfaces of the stent, thus there is less inhibition of
      endothelial cells which need to grow on the inside of the stent in order for healing to
      occur.

      Animal studies have shown the Biofreedom stent demonstrates equivalent or less early and late
      reduction of intimal smooth muscle cell proliferation compared with the Cypher
      Sirolimus-eluting stent (SES) in a porcine model. After implantation of BioFreedom stent,
      delayed arterial healing has been shown to be minimal, and there was no increased
      inflammation at 180 days compared with SES implantation (6). Pharmacokinetic and tissue
      concentration analyses showed that there was no high early peaking of Biolimus A9 level in
      blood (6). On-going studies of Biofreedom in humans showed non-inferiority of in-stent late
      lumen loss at 12 months versus paclitaxel eluting stents (PES) (7).

      This current EGO BIOFREEDOM study protocol is designed based on the approved protocols of the
      EGO Study and EGO-COMBO Study, which were both successfully completed. We aim to focus mainly
      on the time frame, degree of endothelialization, and the subsequent neointimal proliferation
      after BioFreedom stent implantation, as assessed by the state-of-the-art intracoronary
      imaging - optical coherence tomography (OCT), which has been used extensively in the
      completed EGO and EGO-COMBO study.

      Indeed, intracoronary optical coherence tomography (OCT) is a simple catheter-based imaging
      technique using optic fibre to achieve very detailed assessment (resolution down to 100
      microns) in intra-coronary stent apposition, early stent coverage (endothelialization) and
      late stent neoinitmal growth (restenosis). It is performed as part of 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 (8). The LightLab C7XR OCT
      system (Frequency Domain OCT) is a commercial available product with CE Mark and FDA
      approval, which has been used in the EGO Studies. The OCT catheter is a non-occlusive optic
      fibre which is extremely small and flexible. It poses no additional risk to the patient other
      than those inherent risks of a standard angioplasty procedure.
    

Intervention name(s): coronary intervention
Intervention type(s): Device
Intervention description(s): The BioFreedom drug coated stent (DCS) Coronary Stent Delivery System is comprised of three key components
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Optical Coherence Tomography; Biofreedom Stent