title: Comparing different dosing regimens of bevacizumab in the treatment of neovascular macular degeneration: study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Bevacizumab (Avastin®) is as effective as ranibizumab (Lucentis®) in the treatment of neovascular age-related macular degeneration (nAMD). However it has two important structural differences. First, it has two active sites instead of one; second, it retains the Fc portion of the antibody which would be expected to confer a significantly longer half-life. These agents have been associated with systemic complications including strokes, so it is desirable to use the smallest effective dose. Furthermore, the standard dosing regimen requires monthly hospital visits, which present a significant challenge both to the hospital services and to the patients (who are elderly).
  
  
  METHODS
  Patients ≥50 years who are eligible for anti-vascular endothelial growth factor (VEGF) treatment of nAMD in the NHS, who are either newly referred for treatment or have reactivation of nAMD and who have not received treatment to either eye for the previous six months. We have designed a factorial multi-centre masked randomised controlled trial using bevacizumab as the intervention, with patients randomised to one of four arms: to standard or low dose and to monthly or two-monthly patient review. The aim is to recruit sufficient patients (around 1,000) to obtain 304 patients meeting the endpoint over a four-year period. The primary endpoint is time to treatment failure to be analysed using Cox regression.
  
  
  CONCLUSIONS
  This randomised control trial will show if half dose and two monthly as required is as effective as full dose and monthly regimes. A two monthly as required regimen of Bevacizumab would significantly reduce both the cost and the service delivery burden for the treatment of nAMD while a reduced dose would be expected to enhance the safety profile of this treatment regime.
  
  
  BACKGROUND
  International Standard Randomised Controlled Trial Number: ISRCTN95654194 , registered on 22 September 2009.
authors: Department of Ophthalmology, Queen's Medical Centre, Middleton Boulevard, Nottingham, NG7 2UH, England. Alexander.Foss@nottingham.ac.uk.
authors: Alexander J E
authors: AJ
authors: Foss
authors: Nottingham Clinical Trials Unit, Queen's Medical Centre, C-Floor, South Block, Nottingham, NG7 2UH, England. Margaret.childs@nottingham.ac.uk.
authors: Margaret
authors: M
authors: Childs
authors: Clinical Trials and Evaluation Unit, University of Bristol, Bristol Royal Infirmary, Level 7, Bristol, BS2 8HW, England. Barney.Reeves@bristol.ac.uk.
authors: Barnaby C
authors: BC
authors: Reeves
authors: Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, England. theo.empeslidis@uhl-tr.nhs.uk.
authors: Theo
authors: T
authors: Empeslidis
authors: Lincoln County Hospital, Greetwell Road, Lincoln, LN2 5QY, England. Paul.Tesha@ULH.nhs.uk.
authors: Paul
authors: P
authors: Tesha
authors: Department of Ophthalmology, Kings Mill Hospital, Mansfield Road, Sutton-in-Ashfield, NG17 4JL, England. Sushma.Dhar-Munshi@sfh-tr.nhs.uk.
authors: Sushma
authors: S
authors: Dhar-Munshi
authors: Nottingham Clinical Trials Unit, Queen's Medical Centre, C-Floor, South Block, Nottingham, NG7 2UH, England. Samah.mughal@nottingham.ac.uk.
authors: Samah
authors: S
authors: Mughal
authors: Clinical Trials and Evaluation Unit, University of Bristol, Bristol Royal Infirmary, Level 7, Bristol, BS2 8HW, England. lucy.culliford@bristol.ac.uk.
authors: Lucy
authors: L
authors: Culliford
authors: Clinical Trials and Evaluation Unit, University of Bristol, Bristol Royal Infirmary, Level 7, Bristol, BS2 8HW, England. Chris.Rogers@bristol.ac.uk.
authors: Chris A
authors: CA
authors: Rogers
authors: Nottingham Clinical Trials Unit, Queen's Medical Centre, C-Floor, South Block, Nottingham, NG7 2UH, England. Wei.tan@nottingham.ac.uk.
authors: Wei
authors: W
authors: Tan
authors: Nottingham Clinical Trials Unit, Queen's Medical Centre, C-Floor, South Block, Nottingham, NG7 2UH, England. Alan.montgomery@nottingham.ac.uk.
authors: Alan
authors: A
authors: Montgomery
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D000068258:Bevacizumab / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D002985:Clinical Protocols; D017046:Cost Savings; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D016527:Drug Costs; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000503:physiopathology; D008875:Middle Aged; D016016:Proportional Hazards Models; D012107:Research Design; D012307:Risk Factors; D018401:Sample Size; D013222:State Medicine; D013997:Time Factors; D017211:Treatment Failure; D006113:United Kingdom
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab