Please select the arm or intervention descriptions that belong to the clinical trial below.
Title: Short-term Evaluation of Combination Corticosteroid+Anti-VEGF Treatment for Persistent Central-Involved Diabetic Macular Edema Following Anti-VEGF Therapy
Brief Summary: Although anti-vascular endothelial growth factor (VEGF) therapy is generally effective as treatment for center-involved diabetic macular edema (DME), a substantial proportion of anti-VEGF-treated eyes with DME do not achieve vision of 20/20 or complete resolution of retinal thickening. Indeed, over 50% of ranibizumab-treated eyes did not achieve a 2 or more line improvement in visual acuity from baseline at 2 years in Protocol I, a previous DRCR.net (Diabetic Retinopathy Clinical Research Network) study. Furthermore, 27% of ranibizumab-treated eyes still had central subfield (CSF) thickness on time-domain optical coherence tomography (OCT) ≥ 300 at 1 year, and more than 40% of ranibizumab-treated eyes did not achieve complete resolution of retinal thickening (\< 250 microns) by 2 years. Thus, there is a need for alternative or additional treatments that will improve vision by reducing retinal edema in eyes with persistent DME following previous anti-VEGF therapy. Intravitreal steroid is not as efficacious as ranibizumab in eyes with DME overall, but it has been shown to have a positive effect for DME in some eyes and might add benefit in eyes that are already receiving anti-VEGF.

The main objective of this study is to assess the short-term effects of combination steroid+anti-VEGF therapy on visual acuity and retinal thickness on OCT in comparison with that of continued anti-VEGF therapy alone in eyes with persistent central-involved DME and visual acuity impairment despite previous anti-VEGF treatment. This study will provide important information for the design of a future confirmatory phase III clinical trial on the efficacy of combination steroid and anti-VEGF in eyes with persistent DME and vision impairment following previous anti-VEGF therapy. The primary outcome for efficacy will be the mean change in visual acuity at 24 weeks.

Each study eye is required to complete a 12-week run-in phase. The run-in phase will identify study eyes that truly have persistent DME despite anti-VEGF therapy by requiring an additional 3 injections while also collecting standardized visual acuity and OCT measurements. At the enrollment, 4-week and 8-week visits of the run-in phase, enrolled eyes will receive an intravitreal injection of ranibizumab 3mg. Then at the 12-week run-in visit, if the eye still has persistent DME, it will be randomized to receive either intravitreal sham+intravitreal ranibizumab 0.3 or intravitreal dexamethasone+intravitreal ranibizumab 0.3 injections. The randomized study duration is 24 week, during which a protocol visit takes place every month. The combination injections of sham+ranibizumab or dexamethasone +ranibizumab will be given at the randomization visit (baseline) and at the 12-week visit after randomization. In between, an intravitreal injection of ranibizumab only will be given to study eyes at the 4, 8, 16 and 20 week visits.


Options:
A: Intervention Type: DRUG; Name: bevacizumab; Assigned to Arm(s): N/A | Intervention Type: DRUG; Name: triamcinolone acetonide; Assigned to Arm(s): N/A
B: Arm Label: AVASTIN; Type: ACTIVE_COMPARATOR; Interventions: Drug: bevacizumab | Arm Label: OZURDEX; Type: ACTIVE_COMPARATOR; Interventions: Drug: dexamethasone | Intervention Type: DRUG; Name: bevacizumab; Assigned to Arm(s): AVASTIN | Intervention Type: DRUG; Name: dexamethasone; Assigned to Arm(s): OZURDEX
C: Arm Label: Sham + intravitreal ranibizumab 0.3 mg; Type: ACTIVE_COMPARATOR; Interventions: Drug: intravitreal ranibizumab 0.3 mg, Procedure: Sham injection | Arm Label: Intravitreal dexamethasone+intravitreal ranibizumab 0.3mg; Type: EXPERIMENTAL; Interventions: Drug: intravitreal ranibizumab 0.3 mg, Drug: dexamethasone intravitreal implant | Intervention Type: DRUG; Name: intravitreal ranibizumab 0.3 mg; Assigned to Arm(s): Intravitreal dexamethasone+intravitreal ranibizumab 0.3mg, Sham + intravitreal ranibizumab 0.3 mg | Intervention Type: DRUG; Name: dexamethasone intravitreal implant; Assigned to Arm(s): Intravitreal dexamethasone+intravitreal ranibizumab 0.3mg | Intervention Type: PROCEDURE; Name: Sham injection; Assigned to Arm(s): Sham + intravitreal ranibizumab 0.3 mg
D: Intervention Type: DRUG; Name: Triamcinolone, Bevacizumab; Assigned to Arm(s): N/A

Answer: C