StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR): Study protocol for a randomized controlled clinical trial

Background
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.

Methods/Design
STAR is a multicentre, double-masked, randomised, sham-controlled clinical trial. It evaluates a new device (Oraya, Newark, California, 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 Gray 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.

Discussion
The safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD.