Clinical Studies:
RISE/RIDE
Citation: Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789-801. doi:10.1016/j.ophtha.2011.12.039
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Objective
To evaluate the safety and efficacy of intravitreal ranibizumab in patients with diabetic macular edema (DME), primary outcome was percent of patients gaining 15 ETDRS letters
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STUDY DESIGN
Two similarly designed, double-masked, randomized, phase 3 trials in the United States and South America
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DURATION
24 months
STUDY SUBJECTS
- Major inclusion criteria: Adult patients with type 1 or 2 diabetes mellitus with DME (CST >275 microns) with visual acuity between 24 and 73 ETDRS letters (20/40 – 20/320)
- Major exclusion criteria: Previous treatment with anti-VEGF, steroids, and panretinal or macular laser within 3 months. Previous VR surgery. Patients with uncontrolled HTN or DM (A1c > 12.5) or recent CVA or MI (within 3 months).
RANDOMIZATION SCHEME AND INTERVENTIONS
Randomized 1:1:1 to:
(a) sham injections every 4 weeks
(b) ranibizumab 0.3 mg every 4 weeks
(c) ranibizumab 0.5 mg every 4 weeks
Macular laser criteria (after initial 3 months): central foveal thickness >250 microns with <50 micron change from prior month and no previous macular laser in previous 3 months
RESULTS
Study population
- 377 patients – RISE; 382 patients – RIDE
- Similar demographics between cohorts, although more patients had BCVA <20/200 in the 0.3 mg ranibizumab cohort in RISE and in both RISE/RIDE, more eyes in the 0.5 mg ranibizumab cohort had a previous history of intraocular/periocular steroid use
Visual acuity end-points
- Gain >15 letters (0.3 mg, 0.5 mg, and sham respectively): 44.8% and 39.2% versus 18.1% in RISE, and 33.6% and 45.7% versus 12.3% in RIDE
- Average adjusted benefit (at 24 months) over sham was 8.5 – 9.9 letters for ranibizumab treated eyes
- More eyes in ranibizumab cohorts achieved VA >20/40 at 24 months (p < 0.0001 for each ranibizumab cohort vs sham)
Anatomic end-points
- Change in CST from baseline (0.3 mg, 0.5 mg, and sham respectively): −250.6±212.2, −253.1±183.7, and −133.4±209.0 μm, (P < 0.0001) in RISE and −259.8±169.3, −270.7±201.6, and −125.8±198.3 μm, (P < 0.0001) in RIDE
- Resolution of leakage on FA and presence of macular edema on OCT were significantly less in all ranibizumab cohorts compared to sham
Adverse events
- Antiplatelet Trialists’ Collaboration criteria (APTC) events: 4.9% (sham), 2.4% (0.3 mg), 8.7% (0.5 mg) in RISE and 5.5% (sham), 8.8% (0.3 mg), 5.6% (0.5 mg)
- Similar rates of inflammation, cataract, and glaucoma across the cohorts
CONCLUSIONS
- Ranibizumab has beneficial effects on patients with DME, improving visual acuity and maintaining visual improvement for 2 years