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

Abstract

BackgroundThe 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/designSTAR 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.DiscussionThe safety and efficacy outcomes will help determine the role of SRT in the management of chronic, active nAMD.Trial registrationInternational Standard Randomised Controlled Trial Number: ISRCTN12884465. Registered on 28 November 2014. ClinicalTrials.gov: NCT02243878. Registered on 17 September 2014.

Low-Energy Stereotactic Radiotherapy for Treatment of Exudative Age-Related Macular Degeneration in a Treat-and-Extend Regimen

“…These aspects need to be evaluated in a prospective trial, and the currently ongoing STAR study might answer these questions. 30 As we did not follow patients without anti-VEGF treatment after SRT within our analysis, it is not possible to distinguish between the "SRTonly" drying effect or the possibility of anti-VEGFfacilitating effects of SRT. Concerning safety outcomes in terms of microvascular abnormalities, the follow-up period in the analysis was too short to allow for assessments, and these changes may not be detected on clinical examination.…”

A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015

“…Given the high cost of the drugs, it is imperative that clinical services are organised to deliver care efficiently. For example, nurse-administered injections, 36 treat and extend protocols, 37 optometrist-led monitoring 38 and stereotactic radiotherapy, 39 all offer the potential to reduce costs and require stronger evidence. The wide variation between CCGs in the number of injections per patient represents a natural experiment.…”

Recent developments in age-related macular degeneration: a review

“…Other treatment modalities under investigation include the role of adjunctive treatments alongside anti-VEGF by stereotactic radiotherapy (ie, use of a low-voltage external beam) to reduce the frequency of intravitreal injections needed while maintaining VA. 175 , 176 Ranjbar et al 177 demonstrated that the mean number of intravitreal injections was reduced by almost 50% during the 12 months after stereotactic radiotherapy compared to the number required the year before and that VA increased by one line (logMAR). Other promising therapeutic approaches are modulators of angiogenesis.…”