Clinical Studies:
DRCR.NET PROTOCOL T-1 YEAR
Citation: The Diabetic Retinopathy Clinical Trial Network. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. NEJM 2015; 372: 1193-1203.
Key Points
- DRCR.net Protocol T is a randomized, controlled clinical trial that compared aflibercept, bevacizumab, and ranizibumab for diabetic macular edema (DME)
- From months 0 through 6, eyes were treated at baseline and then monthly thereafter unless criteria to hold treatment were met. From months 6 – 12, eyes were evaluated monthly and treated unless there had been no improvement nor worsening in vision and imaging in response to the past 2 injections, and treatment was re-initiated if there was worsening.
- At 1 year, there was no difference in visual outcomes between aflibercept, ranibizumab, and bevacizumab for DME in eyes with baseline vision 20/32-20/40, but better visual outcomes at one year in eyes with vision ≤20/50 for aflibercept, relative to ranibizumab or bevacizumab.
- There were no significant differences between drugs in adverse outcomes, including systemic APTC events
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Objective
To compare outcomes for aflibercept, bevacizumab, and ranibizumab for DME
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STUDY DESIGN
Multicenter, randomized, controlled clinical trial
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DURATION
12 months (24 month data reported separately)
STUDY SUBJECTS
- DM1/DM2 with center-involving DME
- no anti-VEGF therapy in the preceding 12 months
Major inclusion criteria:
STUDY INTERVENTIONS
Randomized 1:1:1 to
- aflibercept 2mg
- ranibizumab 0.3mg
- bevacizumab 1.25mg
(if the non-study eye needed treatment during the study period, the same medication was used)
Treatment schedule
- Injection at baseline
Then:
- From month 0 through week 24 (month 6), monthly visits and treatment q4w unless all 3 criteria below met
- VA ≥20/20
- CRT below eligibility threshold
- No improvement nor worsening in response to the past 2 injections
- (improvement = increase in VA of ≥ 5 letters or CRT decrease by ≥ 10%; worsening = decrease in VA of ≥ 5 letters or CRT increase by ≥ 10%)
- From week 24 (month 6) through study conclusion (12 months), treatment unless no improvement nor worsening in response to the past 2 injections (improvement = increase in VA of ≥ 5 letters or CRT decrease by ≥ 10%; worsening = decrease in VA of ≥ 5 letters or CRT increase by ≥ 10%). Treatment re-initiated if VA or CRT worsened, however.
Laser (focal, grid, or both) performed at or after 24 months based on protocol-defined criteria. Other treatment for DME allowed if the study eye met criteria for treatment failure.
VA/OCT technicians were masked; study coordinators/investigators masked (in the first year)
RESULTS
Study population
- 666 participants
- Study completion was 96%
Visual acuity end-points
- Overall, mean VA improvement was better for aflibercept than for bevacizumab and ranibizumab (p=0.03), however this was not clinically meaning ful because the difference was driven by eyes with worse VA at baesline (see below). There was no difference between ranibizumab and bevacizumab
- For VA 20/32 – 20/40, mean VA improvement was similar in all groups: +8.0 letters aflibercept, +7.5 bevacizumab, +8.3 ranibizumab
- For VA ≤20/50, mean VA improvement was better for aflibercept (+18.9 letters) than ranibizumab (+14.2) or bevacizumab (+11.8). There was no statistically significant difference between ranibizumab and bevacizumab
Anatomic end points
- For VA 20/32 – 20/40, mean reduction in CST: aflibercept > bevacizumab, ranibizumab > bevacizumab. No statistically significant difference between aflibercept and ranibizumab
- For VA ≤20/50, mean reduction in CST: aflibercept > bevacizumab, ranibizumab > bevacizumab. No statistically significant difference between aflibercept and ranibizumab
Systemic adverse events
- Similar in all groups. APTC events were 3-5%
CONCLUSIONS
- There was no difference between aflibercept, ranibizumab, and bevacizumab for DME in eyes with baseline vision 20/32-20/40, but better visual outcomes at one year in eyes with vision ≤20/50 for aflibercept, relative to ranibizumab or bevacizumab