Study to Show a Superior Benefit in Terms of Reduction of Ranibizumab Injections in Patients Receiving Ranibizumab Plus Laser Photocoagulation Combination Therapy Without Loss of Efficacy and Safety
Condition: Macular Edema Secondary to Branch Retinal Vein Occlusion (BRVO)
MeSH terms: Neoplasm Metastasis; Macular Edema; Retinal Vein Occlusion; Edema
Intervention: Ranibizumab; Grid&Direct short pulse laser photocoagulation
Intervention description: Ranibizumab is a biologic and known anti-VEGF (vascular endothelial growth factor) medication approved for treatment of ME (Macular Edema) due to RVO (Retinal Vein occlusion)
0.5 mg ranibizumab applied one + PRN as intravitreal injection of 0.05 mL, with or without laser treatment; Grid&Direct short pulse laser photocoagulation is a kind of laser treatment to retina within vascular arcades and used to suppress macular edema
Intervention MeSH terms: Ranibizumab
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Ranibizumab; Grid&Direct short pulse laser photocoagulation; Macular edema; Branch retinal vein occlusion; BRVO; BCVA; CSFT; pro re nata

Summary:

      This is a Phase IV, randomized, open-label, active-controlled, 2-arm, multicenter study. The
      primary objective was assessed by the difference in the mean number of ranibizumab injections
      applied up to Month 11 between the 2 treatment arms. Patients were randomized in a 1:1 ratio
      to 1 of the 2 treatment arms; i.e. Arm 1 ranibizumab monotherapy, Arm 2 ranibizumab with
      Grid&Direct short pulse laser photocoagulation combination therapy. There were 3 periods in
      this study: Screening Period (visit 1), Treatment Period (visit 2 to Visit 13) and Follow-up
      Period (visit 14). In addition to screening and Baseline (visit 2), there were monthly visits
      from Month 1 to Month 12. This study included male and female patients (≥20 years old)
      diagnosed with visual impairment due to ME secondary to BRVO.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of visual impairment exclusively due to ME secondary to BRVO

          -  Best-corrected visual acuity score at Screening and Baseline (Day 1) between 0.5 and
             0.05 decimal (i.e., between 73 and 19 letters in Early Treatment Diabetic Retinopathy
             Study (ETDRS) testing) with Landolt C charts inclusively (i.e., approximate logarithm
             of the minimum angle of resolution (logMAR) units of 0.3 to 1.30).

          -  At Baseline (Day1), a maximum BCVA gain of 0.2 units logMAR conversion inclusively
             from screening is allowed as long as the BCVA score does not exceed the upper limit of
             0.3 units logMAR.

          -  Increased central subfoveal thickness (> 300 µm at Baseline (Day 1) when measured by
             SD-OCT)

          -  Duration of vision deterioration ≤6 months (determined by self-report) at screening

        Exclusion Criteria:

          -  Pregnant or nursing (lactating) women

          -  Stroke or myocardial infarction less than 3 months before Screening

          -  Uncontrolled blood pressure defined as systolic value of >160 mm Hg or diastolic value
             of >100 mm Hg at Screening or Baseline (Day 1) Antihypertensive treatment can be
             initiated and must be taken for at least 30 days after which the patient can be
             assessed for study eligibility a second time

          -  Any active periocular or ocular infection or inflammation (e.g., blepharitis,
             conjunctivitis, keratitis, scleritis, uveitis, endophthalmitis) at the time of
             Screening or Baseline (Day 1) in either eye

          -  Uncontrolled glaucoma (intraocular pressure (IOP) ≥30 mm Hg on medication or according
             to investigator's judgment) at the time of Screening or Baseline (Day 1) or diagnosed
             within 6 months before Baseline (Day 1) in either eye

          -  Neovascularization of the iris or neovascular glaucoma in the study eye

          -  Use of any systemic anti-VEGF drugs within 6 months before Baseline (Day1) (e.g.,
             sorafenib (Nexavar®), sunitinib (Sutent®), bevacizumab (Avastin®), ziv-aflibercept
             (ZALTRAP®))

          -  Treatment (or anticipated treatment in the fellow eye for non-RVO indications during
             the study) with any anti-angiogenic drugs (including any anti-VEGF agents) within 3
             months before Baseline (Day1) in fellow eye or before Baseline (Day 1) in the study
             eye (e.g., pegaptanib (Macugen®), ranibizumab (Lucentis®), bevacizumab (Avastin®), and
             aflibercept (EYLEA®))

          -  Panretinal laser photocoagulation within 1 month before Baseline (Day1) or anticipated
             or scheduled within the next 12 months (Study periods) following Baseline (Day1) in
             the study eye

          -  Any giving of focal or grid laser photocoagulation before Baseline (Day1) in the study
             eye

          -  Use of intra- or periocular corticosteroids (including sub-Tenon) within 3 months
             before Screening in the study eye.

          -  Any use of intraocular corticosteroid implants (e.g., dexamethasone (Ozurdex®),
             fluocinolone acetonide (Iluvien®)) in the study eye