tereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial
NCT02243878 | STAR | Jackson TL et al. (2024)
Jackson, T. L., Desai, R., Wafa, H. A., Wang, Y., Peacock, J., Peto, T., Chakravarthy, U., Dakin, H., Wordsworth, S., Lewis, C., Clinch, P., Ramazzotto, L., Neffendorf, J. E., Lee, C. N., O’Sullivan, J. M., Reeves, B. C. Stereotactic radiotherapy for neovascular age-related macular degeneration (STAR): a pivotal, randomised, double-masked, sham-controlled device trial. Lancet, 2024; 404:44-54.
Locations
30 hospitals in the UK
Study Period
January 2015 to December 2019
Study Design
Pivotal, randomised, double-masked, sham-controlled device trial
Study Population
Experimental Group
Control Group
Follow-up Time: 96 weeks
Outcomes
Durability
Mean Number of Anti-VEGF Injections
The cumulative mean of injections (Primary Outcome):
• SRT = 10.7 (SD 6.3)
• Sham = 13.3 (SD 5.8)
• Difference = -2.9 (95% CI: -4.2 to -1.6, p<0.0001).
Vision
Best-Corrected Visual Acuity (BCVA)
Mean BCVA change at 96 weeks:
• SRT = -2.9 letters, Sham = -1.5 letters
• Difference = -1.7 (95% CI: -4.2 to 0.8, p = 0.17) and within the five-letter non-inferiority margin.
Proportion Losing <15 Letters SRT = 87%, Sham = 93%.
Proportion Gaining ≥0 Letters SRT = 45%, Sham = 48%.
Proportion Gaining ≥15 Letters SRT = 3%, Sham = 3%.
Other
Quality of Life (QoL)
The week 96 VFQ-25 and EQ-5D-5L scores were similar between the two groups:
• SRT: a median VFQ-25 composite score of 88 (IQR 73–94) and EQ-5D-5L score of 85 (75–95)
• Sham: a median VFQ-25 composite score of 86 (IQR66–94) and EQ-5D-5L score 80 (IQR70–90)
Resource utility
From our costing analysis, SRT was estimated to cost £1343 per participant
Immunognicity
Not reported
Pharmokinetics
Not reported
Anatomic
The mean CFT at week 96 :
• SRT = 237 (95% CI: 219–256) µm
• Sham = 272 (95% CI: 241–303) µm
Angiographic Lesion
Angiographic lesion sizes at week 96:
• SRT = 8.3 mm2(IQR 4.7-12.0)
• Sham=7.3 mm² (IQR 4.1-11.0)
Total active lesion size at week 96:
• SRT = 7.3 mm² (IQR 4.5-12.0)
• Sham = 6.4 mm² (IQR 3.6-11.0)
Others
The benefit is driven by less subretinal fluid and reduced pigment epithelial detachment height with SRT.
Safety
AEs
Total number of events (n):
• SRT = 817
• Sham = 133
SAEs
Total number of events (n):
• SRT = 214
• Sham =73
Ocular AEs (both AEs and SAEs)
Eye disorders:
• SRT = 131/276, 48%
• Sham = 60/133, 45%
Non-Ocular AEs (both AEs and SAEs)
Arterial thromboembolic event:
• SRT = 9/276, 3%
• Sham = 5/133, 4%
AEs (study eyes)
Total number of events (n):
• SRT = 148
• Sham = 62
Ocular events:
• SRT = 33/276, 8.3%
• Sham = 6/133, 4.5%
• SRT = 817
• Sham = 133
Conclusion
SRT significantly reduced the number of anti-VEGF injections required over 96 weeks without compromising visual acuity. Adverse events were similar between groups, but more microvascular abnormalities were seen with SRT. Cost analysis suggests that SRT can reduce the treatment burden and offset the cost of injections.
Risk of Bias Assessment for Primary Outcome
Randomization Process
Low risk
Note: “Participants were individually randomly allocated using
the Clinical Trials Unit’s online randomisation system…” and the baseline characteristics looks balanced.
Missing Outcome Data
Low risk
Note: Evidence that the result was not biased by missing outcome data: “The primary analysis was supplemented with sensitivity analyses to verify the robustness of the results to missing data and non-compliance, comprising base ITT model with additional adjustments, multiple imputation, per-protocol and the pandemic compliance analyses detailed above”
Selection of the Reported Results
Low risk Note: have registration with protocol.
Deviations from Intended Observations
Low risk Note: Both patients and the assessors were masked. In addition, “The primary analysis used the intention-to-treat (ITT) principle…”
Measurement of the Outcome
Low risk Note: Measurement for “Number of Injections” is unlikely be biased.
Overall
Low risk
Categories: Wet AMD