title: Clinical efficacy and mechanistic evaluation of aflibercept for proliferative diabetic retinopathy (acronym CLARITY): a multicentre phase IIb randomised active-controlled clinical trial.
abstract: BACKGROUND
  Proliferative diabetic retinopathy (PDR) is the main cause of severe visual loss in people with diabetes mellitus. The standard treatment for this condition is panretinal photocoagulation (PRP). This laser treatment is inherently destructive, with predictable adverse effects on visual function, and a safer alternative is required. Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors can induce short-term regression of retinal neovascularisation. The aim of this randomised controlled trial is to determine the efficacy, safety and cost-effectiveness of intravitreal aflibercept, an inhibitor of VEGF-A, VEGF-B and placental growth factor (PLGF), in PDR, and to investigate the impact on local oxygenation.
  
  
  METHODS
  This is a phase IIb randomised controlled single-masked multicentre clinical trial to determine the impact of repeated intravitreal aflibercept injections in the treatment and prevention of PDR. 220 participants with treatment-naïve or treated but active retinal neovascularisation in at least one eye will be randomly allocated 1:1 to intravitreal aflibercept injections or PRP for a period of 52 weeks. The primary outcome is the change in best-corrected visual acuity in the study eye at 52 weeks. Secondary outcomes include changes from baseline in other visual functions, anatomical changes and cost-effectiveness. Ocular and non-ocular adverse events will also be reported over 52 weeks.
  
  
  BACKGROUND
  The study has been approved by the National Research Ethics Service (NRES) committee with respect to scientific content and compliance with applicable research and human subjects' regulations. Findings will be reported through scientific publications and research conferences. The results of this study will provide clinical evidence for the feasibility, efficacy safety and cost-effectiveness of intravitreal aflibercept for PDR.
  
  
  BACKGROUND
  ISRCTN 32207582.
authors.affiliation: NIHR Moorfields Biomedical Research Centre, London, UK.
authors.forename: Sobha
authors.initials: S
authors.lastname: Sivaprasad
authors.affiliation: KCL Department of Primary Care and Public Health Sciences, NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, and King's College London, London, UK.
authors.forename: A Toby
authors.initials: AT
authors.lastname: Prevost
authors.affiliation: NIHR Moorfields Biomedical Research Centre, London, Institute of Ophthalmology, London, UK.
authors.forename: James
authors.initials: J
authors.lastname: Bainbridge
authors.affiliation: Centre for Health Economics and Medicines Evaluation, Bangor University, Bangor, Gwynedd, UK.
authors.forename: Rhiannon Tudor
authors.initials: RT
authors.lastname: Edwards
authors.affiliation: Department of Diabetes and Endocrinology, King's College Hospital NHS Foundation Trust, London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Hopkins
authors.affiliation: King's Clinical Trials Unit at KHP, Kings College London, Institute of Psychiatry, London, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kelly
authors.affiliation: Institute of Ophthalmology, London, UK.
authors.forename: Phil
authors.initials: P
authors.lastname: Luthert
authors.affiliation: King's Clinical Trials Unit at KHP, Kings College London, Institute of Psychiatry, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Murphy
authors.affiliation: NIHR Moorfields Biomedical Research Centre, London, UK.
authors.forename: Jayashree
authors.initials: J
authors.lastname: Ramu
authors.affiliation: King's Clinical Trials Unit at KHP, Kings College London, Institute of Psychiatry, London, UK.
authors.forename: Negin
authors.initials: N
authors.lastname: Sarafraz-Shekary
authors.affiliation: KCL Department of Primary Care and Public Health Sciences, NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust, and King's College London, London, UK.
authors.forename: Joana
authors.initials: J
authors.lastname: Vasconcelos
authors.affiliation: King's Clinical Trials Unit at KHP, Kings College London, Institute of Psychiatry, London, UK.
authors.forename: Beverley
authors.initials: B
authors.lastname: White-Alao
authors.affiliation: NIHR Moorfields Biomedical Research Centre, London, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Hykin
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008297:Male; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity / Q000187:drug effects*
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C533178:aflibercept; D040262:Receptors, Vascular Endothelial Growth Factor