A Study of the Efficacy and Safety of Ranibizumab Injection in Patients With Macular Edema Secondary to Branch Retinal Vein Occlusion (BRAVO)

This study has been completed.
Sponsor:
Information provided by:
Genentech
ClinicalTrials.gov Identifier:
NCT00486018
First received: June 11, 2007
Last updated: April 25, 2011
Last verified: April 2011
Results First Received: August 16, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Conditions: Macular Edema
Retinal Vein Occlusion
Interventions: Drug: Ranibizumab injection 0.3 mg
Drug: Ranibizumab injection 0.5 mg
Drug: Sham injection

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Please note that although the table below is titled "Overall Study," the completion rates are for the 6-month Treatment Period only (i.e., does not include the 6-month Observation Period data).

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Sham Injection Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.
Ranibizumab Injection 0.3 mg Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Ranibizumab Injection 0.5 mg Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.

Participant Flow:   Overall Study
    Sham Injection     Ranibizumab Injection 0.3 mg     Ranibizumab Injection 0.5 mg  
STARTED     132     134     131  
Received Drug (Safety Population)     131     134     130  
COMPLETED     123     128     125  
NOT COMPLETED     9     6     6  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Sham Injection Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.
Ranibizumab Injection 0.3 mg Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Ranibizumab Injection 0.5 mg Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Total Total of all reporting groups

Baseline Measures
    Sham Injection     Ranibizumab Injection 0.3 mg     Ranibizumab Injection 0.5 mg     Total  
Number of Participants  
[units: participants]
  132     134     131     397  
Age  
[units: years]
Mean ± Standard Deviation
  65.2  ± 12.7     66.6  ± 11.2     67.5  ± 11.8     66.4  ± 11.9  
Age, Customized  
[units: participants]
       
< 45 years     8     5     4     17  
45 to < 65 years     59     51     51     161  
65 to < 85 years     60     74     69     203  
≥ 85 years     5     4     7     16  
Gender  
[units: participants]
       
Female     58     67     60     185  
Male     74     67     71     212  



  Outcome Measures
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1.  Primary:   Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months   [ Time Frame: Baseline and 6 months ]
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Measure Type Primary
Measure Title Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months
Measure Description BCVA score in the study eye was based on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity charts (number of correct letters) and assessed at a starting distance of 4 meters.
Time Frame Baseline and 6 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat (randomized) population. Missing values were imputed using the last-observation-carried-forward (LOCF) method.

Reporting Groups
  Description
Sham Injection Sham injection in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six sham injections.
Ranibizumab Injection 0.3 mg Ranibizumab injection 0.3 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.
Ranibizumab Injection 0.5 mg Ranibizumab injection 0.5 mg in a single-dose regimen given every month (Day 0 through the Month 5 visit), for a total of six injections.

Measured Values
    Sham Injection     Ranibizumab Injection 0.3 mg     Ranibizumab Injection 0.5 mg  
Number of Participants Analyzed  
[units: participants]
  132     134     131  
Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months  
[units: Units on a scale]
Mean ± Standard Deviation
     
Baseline     54.7  ± 12.2     56.0  ± 12.1     53.0  ± 12.5  
Change from Baseline at Month 6     7.3  ± 13.0     16.6  ± 11.0     18.3  ± 13.2  


Statistical Analysis 1 for Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months
Groups [1] Sham Injection vs. Ranibizumab Injection 0.3 mg
Method [2] ANOVA
P Value [3] <0.0001
Difference in Least Squares means [4] 9.4
95% Confidence Interval ( 6.6 to 12.2 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline visual acuity score (≤ 34, 35–54, ≥ 55 letters).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The Hochberg–Bonferroni multiple comparison procedure was used to adjust for comparisons of the two ranibizumab groups with the sham-injection group to maintain an overall type I error rate of 0.05.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) Score at 6 Months
Groups [1] Sham Injection vs. Ranibizumab Injection 0.5 mg
Method [2] ANOVA
P Value [3] <0.0001
Difference in Least Squares means [4] 10.6
95% Confidence Interval ( 7.6 to 13.6 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Stratified by baseline visual acuity score (≤ 34, 35–54, ≥ 55 letters).
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  The Hochberg-Bonferroni multiple comparison procedure was used to adjust for comparisons of the two ranibizumab groups with the sham-injection group to maintain an overall type I error rate of 0.05.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Participants Who Gained ≥ 15 Letters in BCVA Score at Month 6 Compared With Baseline   [ Time Frame: Baseline and 6 months ]

3.  Secondary:   Percentage of Participants Who Lost < 15 Letters in BCVA Score at Month 6 Compared With Baseline   [ Time Frame: Baseline and 6 months ]

4.  Secondary:   Percentage of Participants With a Central Foveal Thickness of ≤ 250 μm at Month 6   [ Time Frame: 6 months ]

5.  Secondary:   Mean Absolute Change From Baseline in Central Foveal Thickness at Month 6   [ Time Frame: Baseline and 6 months ]

6.  Secondary:   Mean Change From Baseline in the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) Near Activities Subscale Score at Month 6   [ Time Frame: Baseline and 6 months ]

7.  Secondary:   Mean Change From Baseline in the NEI VFQ-25 Distance Activities Subscale Score at Month 6   [ Time Frame: Baseline and 6 months ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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