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Copyright ©2013 Baishideng Publishing Group Co.
World J Diabetes. Dec 15, 2013; 4(6): 303-309
Published online Dec 15, 2013. doi: 10.4239/wjd.v4.i6.303
Table 1 Summary of some important trials in which vascular endothelial growth factor antagonists have been evaluated for diabetic macular edema
TrialDrug name
PegaptanibBevacizumab Ranibizumab
Study nameStudy to Evaluate safety and tolerability of pegaptanib sodium in patients with diabetic macular edema[39]BOLT study[23,39]RESOLVE[40]READ-2[21,20]READ-3RISE[22]RIDE[22]
Study type/phaseInterventional /phase 3Interventional /phase 2Interventional /phase 2Interventional /phase 2Interventional /phase 2Interventional /phase 3Interventional /phase 3
Number of patients4680151126142377382
Intervention/study design0.3 mg injections up to a maximum of 48 wk with a minimum-dosing interval of at least 6 wk(1) Intravitreal Bevacizumab (2) MLT(1) 0.3 mg Ranibizumab (2) 0.5 mg Ranibizumab (3) Sham(1) 0.5 mg ranibizumab (group 1) (2) Focal/grid laser (group 2) (3) 0.5 mg ranibizumab + focal/grid laser (group 3)(1) 0.5 mg ranibizumab (2) 2 mg ranibizumab(1) Sham (2) 0.3 mg (3) 0.5 mg(1) Sham (2) 0.3 mg (3) 0.5 mg
ResultsNo results available yetYear 1 endpoint: A median gain of 8 ETDRS letters in the bevacizumab group vs a loss of 0.5 ETDRS letters in the MLT group (P = 0.0002) CMT decreased from 507 ± 145 μm to 378 ± 134 μm (P < 0.001) in the bevacizumab group, whereas it decreased from 481 ± 121 μm to 413 ± 135 μm in the MLT group (P = 0.02)[39] Year 2 endpoint: A Mean gain of 8.6 letters for bevacizumab vs a mean loss of 0.5 letters in the MLT group[23]. A mean reduction of 146 μm in the CMT in the bevacizumab arm vs 118 μm in the MLT armA gain of 10.3 ± 9.1 letters with ranibizumab and a loss of 1.4 ± 14.2 letters in the sham group (P < 0.0001) A mean CMT reduction of 194.2± 135.1 μm with ranibizumab and 48.4 ± 153.4 μm with sham (P < 0.0001) A gain of ≥ 10 letters in BCVA from baseline in 60.8% of eyes in the ranibizumab group and 18.4% of eyes in the sham group (P < 0.0001)The mean improvement in BCVA was 7.4, 0.5, and 3.8 letters at the 6 mo primary end point, compared with 7.7, 5.1, and 6.8 letters at month 24 in group 1, group 2 and group 3 respectively The percentage of patients who gained 3 lines or more of BCVA was 21, 0, and 6 at month 6, compared with 24, 18, and 26 at month 24. Mean FTH, defined as center subfield thickness, at month 24 was 340 μm, 286 μm, and 258 μm for groups 1, 2, and 3, respectivelyThe study has completed Results are being analyzedYear 2 endpoint: 18.1% of sham patients gained ≥15 letters vs 44.8% of 0.3-mg (P < 0.0001) and 39.2% of 0.5-mg ranibizumab patients (P < 0.001)12.3% of sham patients vs 33.6% of 0.3-mg patients (P < 0.0001) and 45.7% of 0.5-mg ranibizumab patients (P < 0.0001) gained more than 15 letters
Table 2 Summary of clinical trials in which aflibercept was evaluated for diabetic macular edema
TrialStudy Name
Phase 1 study of VEGF trap in patients with DMEDA VINCIVIVID-JapanVISTA DMEVIVID-DMEProtocol T
Study typeInterventionalInterventionalInterventionalInterventionalInterventionalInterventional
Study phasePhase 1Phase 2Phase 3Phase 3Phase 3Phase 3
Official titleAn exploratory study of the safety, tolerability and biological effect of a single intravitreal administration of VEGF trap eye in patients with DMEA double-masked, randomized, controlled study of the safety, tolerability and biological effect of repeated intravitreal administration of VEGF trap-eye in patients with DMEA randomized, double masked, active controlled, phase III study of the efficacy and safety of repeated doses of intravitreal VEGF trap-eye in subjects with DMEA double-masked, randomized, active-controlled, phase 3 study of the efficacy and safety of intravitreal administration of VEGF trap-eye in patients with DMEAn open-label phase III study evaluating the safety and tolerability of repeated doses of intravitreal VEGF trap-eye in Japanese subjects with DMEA comparative effectiveness study of intravitreal aflibercept,bevacizumab and ranibizumab for DME
Study design
AllocationNon-randomizedRandomizedRandomizedN/ARandomizedRandomized
Endpoint classificationSafety StudySafety/Efficacy studySafety/Efficacy studySafety/Efficacy studySafety/Efficacy studySafety/Efficacy study
Intervention modelSingle group assignmentParallel assignmentParallel assignmentSingle group assignmentParallel assignmentParallel assignment
MaskingOpen labelDouble blind (subject, investigator, outcomes assessor)Double blind (subject, investigator, outcomes assessor)Open labelDouble blind (subject, investigator, outcomes assessor)single blind (subject)
Primary purposeTreatmentTreatmentTreatmentTreatmentTreatmentTreatment
Enrollment521965466406660
Study period6 wk52 wk48 wk2 yr52 wk2 yr
Recruitment statusCompletedCompletedRecruitingActive, not recruitingActive, not recruitingActive, recruiting
Primary outcome measureTo assess the ocular and systemic safety and tolerability of a single IVT injection of VEGF Trap-eye in patients with DMEChange in BCVAAdverse event collectionChange from baseline of BCVA in ETDRS letter scoreChange from baseline of BCVA in ETDRS letter scoreChange in visual acuity from baseline to one year adjusted for baseline visual acuity
Estimated study completion dateCompletedCompleted2013201420152016