Preoperative Bevacizumab and Ziv-Aflibercept Administration in PDR Subjects Undergoing PPV
Condition: Diabetic Retinopathy
MeSH terms: Retinal Diseases; Diabetic Retinopathy
Study type: Interventional

Summary: 
      To compare outcomes in subjects receiving different doses and treatment intervals of
      intravitreal bevacizumab or ziv-aflibercept preoperatively administered prior to undergoing
      vitrectomy for complications of proliferative diabetic retinopathy.
    

Detailed description: 
      Severe vision loss in patients with proliferative diabetic retinopathy (PDR) frequently
      results from complications related to neovascularization and fibrovascular proliferation.
      Patients with PDR are typically considered candidates for pars plana vitrectomy (PPV) when
      non-clearing vitreous hemorrhaging, tractional retinal detachment (TRD) development or
      extensive fibrovascular proliferation occur. Visual prognosis is guarded in patients
      undergoing PPV with these advanced presentations of PDR because of the high rate of both
      intra-operative and postoperative complications. Intra-operative bleeding may result in poor
      visualization during PPV that increases total surgery time and ultimately leads to surgical
      failure, while recurrent/persistent postoperative vitreous hemorrhage may occur as high as
      75% and hinder visual rehabilitation and monitoring of further disease progression.

      Preoperative administration of bevacizumab (Avastin; Genentech, Inc, South San Francisco,
      California, USA), a full-length recombinant humanized monoclonal antibody targeting vascular
      endothelial growth factor (VEGF), has been reported in prospective clinical trials to
      decrease the overall surgery time, lower the rate of intra-operative complications, and
      reduce the occurrence of postoperative hemorrhaging in PDR patients with active
      neovascularization and/or extensive fibrovascular proliferation undergoing PPV. Furthermore,
      two meta-analysis studies examining published randomized controlled trials support the use of
      intravitreal bevacizumab (IVB) as a preoperative adjunct. Although IVB is widely used as a
      preoperative adjunct in patients with PDR undergoing PPV, little clinical data is available
      regarding the optimal timing of preoperative IVB administration or the most effective dose.
      In this randomized clinical study, we attempt to elucidate the most appropriate interval and
      dose for the administration of preoperative IVB in patients with PDR undergoing PPV for
      non-clearing vitreous hemorrhaging, TRD or extensive fibrovascular proliferation.

      Ziv-aflibercept (Zaltrap, Regeneron) is a recombinant fusion protein that acts as a soluble
      decoy receptor and binds to VEGF-A, VEGF-B, and placental growth factor, similar to
      aflibercept (Eylea, Regeneron, Tarrytown, NY), which is FDA approved for intravitreal
      administration to treat various retinal diseases. At the dose of 1.25 mg/0.05 mL,
      ziv-aflibercept has been reported to safely and effectively treat neovascular macular
      degeneration and diabetic macular edema, similar in efficacy to bevacizumab. Presently, there
      are no reports regarding the effectiveness of preoperative ziv-aflibercept administration
      prior to PPV for PDR. In this randomized clinical trial, we also evaluate the effectiveness
      of ziv-aflibercept to bevacizumab, and attempt to elucidate the most appropriate interval for
      the administration of preoperative ziv-aflibercept in patients with PDR undergoing PPV for
      non-clearing vitreous hemorrhaging, TRD or extensive fibrovascular proliferation.
    

Intervention name(s): Intravitreal bevacizumab or intravitreal ziv-aflibercept
Intervention type(s): Drug
Intervention description(s): Intravitreal bevacizumab or intravitreal ziv-aflibercept is given preoperatively at various time intervals and doses.
Intervention MeSH terms: Bevacizumab; Aflibercept
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment