title: StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): study protocol for a randomised controlled clinical trial.
abstract: The standard of care for neovascular age-related macular degeneration (nAMD) involves ongoing intravitreal injections of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF). The most commonly used anti-VEGF drugs are ranibizumab, bevacizumab and aflibercept. The main objective of the STAR trial is to determine if stereotactic radiotherapy can reduce the number of anti-VEGF injections that patients with nAMD require.
  
  
  
  STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (manufactured by Oraya, Newark, CA, USA) designed to deliver stereotactic radiotherapy (SRT) to nAMD lesions. The trial enrols participants with chronic, active nAMD. Participants receive a single SRT treatment (16 Gy or sham) with a concomitant baseline intravitreal injection of 0.5 mg ranibizumab. Thereafter, they attend every month for 24 months, and ranibizumab is administered at the visit if retreatment criteria are met. The primary outcome is the number of pro re nata ranibizumab injections during the first 24 months. Secondary outcomes include visual acuity, lesion morphology, quality of life and safety. Additional visits occur at 36 and 48 months to inspect for radiation retinopathy. The target sample size of 411 participants (randomised 2:1 in favour of radiation) is designed to detect a reduction of 2.5 injections against ranibizumab monotherapy, at 90% power, and a significance level (alpha) of 0.025 (one-sided two-sample t test). This gives 97% power to detect non-inferiority of visual acuity at a five-letter margin. The primary analyses will be by intention to treat.
  
  
  
  The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD.
  
  
  
  International Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878 . Registered on 17 September 2014.
authors.affiliation: Department of Ophthalmology, King's College Hospital, London, UK.|School of Medicine, King's College London, London, UK.
authors.forename: James E
authors.initials: JE
authors.lastname: Neffendorf
authors.affiliation: Department of Ophthalmology, King's College Hospital, London, UK.
authors.forename: Riti
authors.initials: R
authors.lastname: Desai
authors.affiliation: Division of Health and Social Care Research, King's College London, London, UK.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: King's Clinical Trials Unit, King's College London, London, UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kelly
authors.affiliation: King's Clinical Trials Unit, King's College London, London, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Murphy
authors.affiliation: School of Clinical Sciences, University of Bristol, Bristol, UK.
authors.forename: Barnaby C
authors.initials: BC
authors.lastname: Reeves
authors.affiliation: Central Angiographic Resource Facility, Queen's University of Belfast, Belfast, UK.
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.affiliation: Health Economics Research Centre, University of Oxford, Oxford, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wordsworth
authors.affiliation: Medical Physics and Engineering, King's College Hospital, London, UK.
authors.forename: Cornelius
authors.initials: C
authors.lastname: Lewis
authors.affiliation: Division of Health and Social Care Research, King's College London, London, UK.
authors.forename: Janet
authors.initials: J
authors.lastname: Peacock
authors.affiliation: Department of Ophthalmology, King's College Hospital, London, UK.
authors.forename: Shahir
authors.initials: S
authors.lastname: Uddin
authors.affiliation: Centre for Cancer Research and Cell Biology, Queen's University of Belfast, Belfast, UK.
authors.forename: Joe M
authors.initials: JM
authors.lastname: O'Sullivan
authors.affiliation: Department of Ophthalmology, King's College Hospital, London, UK. t.jackson1@nhs.net.|School of Medicine, King's College London, London, UK. t.jackson1@nhs.net.
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Jackson
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D006801:Humans; D057194:Intention to Treat Analysis; D058449:Intravitreal Injections; D008268:Macular Degeneration / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*; D011788:Quality of Life; D016634:Radiosurgery / Q000009:adverse effects; D000069579:Ranibizumab / Q000008:administration & dosage; D020127:Recovery of Function; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom; D014792:Visual Acuity; D057135:Wet Macular Degeneration / Q000175:diagnosis / Q000503:physiopathology / Q000601:surgery*
chemical_list: D020533:Angiogenesis Inhibitors; D000069579:Ranibizumab
keywords: Anti-vascular endothelial growth factor; Neovascular age-related macular degeneration; Radiation; Ranibizumab; STAR study; Stereotactic radiotherapy; VEGF; Wet age-related macular degeneration