The Use of Bevacizumab as a Modulator of Wound Healing Following Trabeculectomy Surgery
Condition: Glaucoma
MeSH terms: Glaucoma
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a phase III randomised controlled pilot study which aims to assess the effectiveness
      of the use of bevacizumab in patients who have undergone trabeculectomy surgery, which appear
      to be showing early signs of failure.
    

Detailed description: 
      Pharmacological enhancement of trabeculectomy using Mitomycin C (MMC) has significantly
      improved success rates. Despite this, some patients still mount aggressive scarring responses
      post-operatively and require additional subconjunctival injections of antifibrotic agents,
      such as 5-Fluorouracil (5-FU) to reduce scar formation and reduce the likelihood of surgical
      failure. There is concern that these agents are potentially toxic and may result in side
      effects such as keratopathy (loss of corneal epithelium) and are also painful for the
      patient. For those patients that are showing clinical evidence of potential scar formation, a
      more predictable and less toxic modulator of wound healing is desirable.

      Vascular endothelial growth factor (VEGF) has been associated with angiogenesis in numerous
      pathological situations, including tumor growth, proliferative retinopathy, and rheumatoid
      arthritis. VEGF is also thought to play a pivotal role in ocular wound healing. It mediates
      the signal transduction cascade leading to tenon's fibroblast migration and proliferation and
      collagen gel contraction at the site of surgery, as well as angiogenesis. VEGF also causes
      persistent vascular permeability and vasodilation at the level of existing microvessels.
      Vessels with increased permeability are typically tortuous and dilated and this is the
      clinical appearance within the conjunctiva, suggestive of future excessive wound healing and
      scar formation following trabeculectomy. Early interventions such as subconjunctival
      injections of 5-Fluorouracil (5-FU) are therefore often considered when these clinical
      findings are apparent, in order to modify the course of wound healing.

      The investigators propose a pilot study looking at the effect of serial injections of
      bevacizumab (an anti-VEGF agent) on modifying the wound healing response in patients showing
      early signs of future failure, compared to 5-Fluorouracil (5-FU). The purpose of the pilot is
      to also gather outcome data and information relating to safety and recruitment with a view to
      powering a definitive study addressing this issue.
    

Intervention name(s): bevacizumab; 5-fluorouracil; Dexamethasone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Patients will be randomised to study arms with a 1:1 ratio. Once randomised, Group 2 will receive a subconjunctival injection of bevacizumab and a subconjunctival injection of dexamethasone 3.3mg/ml. This will be given for 4 consecutive weeks from time of entry into trial.; Patients will be randomised to study arms with a 1:1 ratio. Once randomised, Group 1 will receive a subconjunctival injection of 5-fluorouracil and a subconjunctival injection of dexamethasone 3.3mg/ml. This will be given as required for 4 consecutive weeks from time of entry into trial. This is current standard practice.; Both intervention groups will be given a subconjunctival injection of dexamethasone at the time of injection of either bevacizumab or 5-fluorouracil
Other intervention name(s): Avastin; 5-FU
Intervention MeSH terms: Dexamethasone; Bevacizumab; Fluorouracil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Ophthalmology