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Efficacy and Safety of Ranibizumab With or Without Laser in Comparison to Laser in Branch Retinal Vein Occlusion (BRIGHTER)

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ClinicalTrials.gov Identifier: NCT01599650
Recruitment Status : Completed
First Posted : May 16, 2012
Results First Posted : November 10, 2016
Last Update Posted : November 10, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Branch Retinal Vein Occlusion
Interventions Drug: Ranibizumab
Procedure: Laser
Enrollment 455
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab
Period Title: Overall Study
Started 183 180 92
Completed 6 Mos 174 170 80
Completed 161 154 65
Not Completed 22 26 27
Reason Not Completed
Administrative issue             1             0             1
Physician Decision             2             0             7
Protocol Violation             0             3             0
Death             2             1             2
Lost to Follow-up             3             3             3
Withdrawal by Subject             11             11             10
Adverse Event             3             8             4
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy Total
Hide Arm/Group Description laser therapy + Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser after 6 months, laser patients could be treated with ranibizumab Total of all reporting groups
Overall Number of Baseline Participants 183 180 92 455
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 183 participants 180 participants 92 participants 455 participants
64.7  (10.34) 67.3  (10.41) 67.7  (9.67) 66.3  (10.30)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 183 participants 180 participants 92 participants 455 participants
Female
90
  49.2%
84
  46.7%
55
  59.8%
229
  50.3%
Male
93
  50.8%
96
  53.3%
37
  40.2%
226
  49.7%
1.Primary Outcome
Title Mean Change in Visual Acuity: BCVA Change at Month 6 Compared to Baseline in Patients With Visual Impairment Due to Branch Retinal Vein Occlusion (BRVO)
Hide Description

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)

-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 6 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.

Time Frame Baseline, 6 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
analysis for change consists of the group that had a baseline and 6 month data point
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Mean (Standard Deviation)
Unit of Measure: letters
Baseline 59.5  (11.78) 56.6  (13.19) 56.8  (13.86)
Month 6 74.3  (12.27) 71.4  (14.43) 62.8  (14.08)
Change from Baseline atMonth 6 14.8  (10.70) 14.8  (11.13) 6.0  (14.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1-ranibizumab Monotherapy, 3-laser Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS mean
Estimated Value 10.0
Confidence Interval (2-Sided) 95%
7.3 to 12.8
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.41
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 2-ranibizumab With Laser, 3-laser Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter difference in LS Means
Estimated Value 8.7
Confidence Interval (2-Sided) 95%
5.8 to 11.6
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.46
Estimation Comments [Not Specified]
2.Secondary Outcome
Title The Mean Average Change in Visual Acuity From Month 1 Through Month 24 Compared to Baseline
Hide Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. (A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 24. Then, mean average change is calculated as the average of average changes across all patients.
Time Frame Baseline, 24 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
analysis for change consists of the group that had a baseline and 24 month data point
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Mean (Standard Deviation)
Unit of Measure: letters
Baseline 59.5  (11.78) 56.6  (13.19) 56.8  (13.86)
Average Month 1 toMonth 24 74.5  (12.11) 72.0  (13.56) 65.9  (13.24)
Change from Baseline 15.0  (10.86) 15.4  (10.76) 9.1  (13.49)
3.Secondary Outcome
Title Number of Ranibizumab Treatments From Day 1 to Month 23 by Treatment Group
Hide Description Number of injections provided to the patients during the 23 month period and conducted within FAS with LOCF and observed data.
Time Frame Day 1 through Month 23
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
Overall Number of Participants Analyzed 180 178
Mean (Standard Deviation)
Unit of Measure: treatments
11.4  (5.76) 11.3  (6.03)
4.Secondary Outcome
Title Mean Average Change in Visual Acuity (BCVA Letters) From Month 1 Through Month 6
Hide Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters.(A positive average change from baseline of BCVA indicates improvement): Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 6. Then, mean average change is calculated as the average of average changes across all patients.
Time Frame From Baseline through Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Mean (Standard Deviation)
Unit of Measure: letters
Baseline 59.5  (11.78) 56.6  (13.19) 56.8  (13.86)
Average Month 1 to Month 6 72.7  (11.49) 69.7  (13.38) 61.7  (12.66)
Change from Baseline 13.2  (9.60) 13.2  (9.89) 4.8  (11.69)
5.Secondary Outcome
Title The Mean Change in Visual Acuity BCVA (Letters) From Baseline at Month 12 and Month 24
Hide Description Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) -like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 12 and Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and were assessed by an ANOVA model.
Time Frame Baseline, Month 12 and Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full Analysis set
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Mean (Standard Deviation)
Unit of Measure: letters
Baseline 59.5  (11.78) 56.6  (13.19) 56.8  (13.86)
Month 12 74.9  (12.87) 72.3  (15.31) 66.8  (13.87)
Change from baseline Month 12 15.4  (12.25) 15.7  (13.12) 10.0  (14.33)
Month 24 75.0  (14.65) 73.9  (14.59) 68.4  (15.26)
Change from baseline Month 24 15.5  (13.91) 17.3  (12.61) 11.6  (16.09)
6.Secondary Outcome
Title The Percent of Patients With a Visual Acuity Gain of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline up to Month 6 and Month 24, by Visit
Hide Description BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at Month 6 & Month 24 as compared with baseline, was assessed by an ANOVA model. Endpoints related to the proportion of patients with BCVA letter gain or loss from Baseline was analyzed via stratified Cochran-Mantel-Haenszel test with stratification based on baseline BCVA (baseline BCVA less than or equal to 39, 40 to 59, greater than or equal to 60 letters, treatment groups).
Time Frame Baseline, Month 6 and Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Measure Type: Number
Unit of Measure: percent patients gaining improvement
BCVA improvement of >= 1 lettermonth 6 93.3 96.1 63.3
BCVA improvement of >= 1 lettermonth 24 89.4 93.8 77.8
BCVA improvement of >= 5 lettersmonth 6 86.1 88.2 50.0
BCVA improvement of >= 5 lettersmonth 24 83.3 89.3 70.0
BCVA improvement of >= 10 lettersmonth 6 66.7 68.5 41.1
BCVA improvement of >= 10 lettersmonth 24 71.1 75.8 60.0
BCVA improvement of >= 15 lettersmonth 6 45.0 47.2 27.8
BCVA improvement of >= 15 lettersmonth 24 52.8 59.6 43.3
BCVA improvement of >= 30 lettersmonth 6 10.0 9.6 3.3
BCVA improvement of >= 30 lettersmonth 24 13.3 14.0 11.1
7.Secondary Outcome
Title Number of Patients With a BCVA Improvement vs Baseline or Achieving Greater Than or Equal to 73 Letters at Month 6 in the Study Eye
Hide Description Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 6 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 6 indicates a positive outcome.
Time Frame Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Measure Type: Number
Unit of Measure: participants
BCVA improvement of ≥ 1 letter 168 171 57
BCVA improvement of ≥ 5 letters N 155 157 45
BCVA improvement of ≥ 10 letters 120 122 37
BCVA improvement of ≥ 15 letters 81 84 25
BCVA improvement of ≥ 30 letters 18 17 3
BCVA score ≥ 73 letters 118 97 28
8.Secondary Outcome
Title Number of Patients With a BCVA Improvement vs Baseline or Achieved Greater Than or Equal to 73 Letters at Month 24 in the Study Eye
Hide Description Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and Month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at Month 24 indicates a positive outcome.
Time Frame Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Measure Type: Number
Unit of Measure: participants
BCVA improvement of ≥ 1 letter 161 167 70
BCVA improvement of ≥ 5 letters 150 159 63
BCVA improvement of ≥ 10 letters 129 135 54
BCVA improvement of ≥ 15 letters 95 106 39
BCVA improvement of ≥ 30 letters 24 25 10
BCVA score ≥ 73 letters 119 114 41
9.Secondary Outcome
Title The Mean Change in Central Reading Center-assessed Central Subfield Thickness From Month 12 and Month 24 vs. Baseline by Treatment Arm
Hide Description Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation. Stratification was done based on categories of baseline best corrected visual acuity & analysis was based on analysis of variance (ANOVA)
Time Frame Month 12 and Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Mean (Standard Error)
Unit of Measure: microns
month 12 -215.9  (12.83) -242.5  (14.14) -203.9  (22.22)
month 24 -228.1  (12.65) -261.7  (15.20) -232.7  (24.38)
10.Secondary Outcome
Title The Mean Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 6 and Month 24 Compared to Baseline
Hide Description The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. All items are scored so that a high score represents better functioning. Each item is then converted to a 0 to 100 scale so that the lowest and highest possible scores are set at 0 and 100 points, respectively. In this format scores represent the achieved percentage of the total possible score, e.g. a score of 50 represents 50% of the highest possible score.
Time Frame Months 6 and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 1-ranibizumab Monotherapy 2-ranibizumab With Laser 3-laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg
Ranibizumab 0.5 mg + laser
after 6 months, laser patients could be treated with ranibizumab
Overall Number of Participants Analyzed 180 178 90
Mean (Standard Deviation)
Unit of Measure: score on a scale
month 6 composite score 5.6  (9.56) 4.2  (10.41) 3.7  (12.12)
month 24 composite score 8.0  (11.78) 5.0  (11.44) 4.9  (14.79)
11.Secondary Outcome
Title BCVA (Letters) Mean Average Change From First Ranibizumab Treatment to Month 24 in the Study Eye for Patients Randomized to the Laser Monotherapy Arm
Hide Description

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)

-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. For the mean change of best corrected visual acuity at Month 24 compare to Baseline, the 95% confidence interval and P value (related to the null hypothesis that this mean change is equal to zero) based on a t distribution/t test were calculated and assessed by an ANOVA model.

Time Frame Month 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Randomized set
Arm/Group Title 3- Laser Monotherapy
Hide Arm/Group Description:
laser therapy + Ranibizumab 0.5 mg after Month 6
Overall Number of Participants Analyzed 66
Mean (Standard Deviation)
Unit of Measure: BCVA letters
Value at 1st Ranibizumab treatment 61.7  (12.21)
Average post 1st treatment through Month 24 68.16  (11.84)
Change from 1st Ranibizumab treatment 6.49  (7.83)
Time Frame [1] Safety set was summarized based on actual treatment received. There were 3 laser monotherapy patients who received ranibizumab and 1 ranibizumab patient who received laser treatment which resulted in percentages > 100% for the ranibizumab + laser arm.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
Hide Arm/Group Description Ranibizumab 0.5mg

Ranibizumab 0.5mg + Laser

[1] Safety set was summarized based on actual treatment received. There were 3 laser monotherapy patients who received ranibizumab and 1 ranibizumab patient who received laser treatment which resulted in percentages > 100% for the ranibizumab + laser arm.

Laser monotherapy with Ranibizumab 0.5 mg from Month 6 Laser monotherapy without Ranibizumab 0.5 mg from Month 6
All-Cause Mortality
Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   30/180 (16.67%)   33/183 (18.03%)   10/63 (15.87%)   3/25 (12.00%) 
Cardiac disorders         
Acute coronary syndrome  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Angina pectoris  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Aortic valve incompetence  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Arrhythmia  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Arteriosclerosis coronary artery  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Atrial fibrillation  1  3/180 (1.67%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Atrioventricular block second degree  1  1/180 (0.56%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Bradycardia  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Cardiac arrest  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Cardiac failure  1  1/180 (0.56%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Coronary artery embolism  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Myocardial infarction  1  1/180 (0.56%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Myocardial ischaemia  1  1/180 (0.56%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Tachycardia  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Eye disorders         
Cataract (Fellow untreated eye)  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Cataract (Study eye)  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Macular fibrosis (Study eye)  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Macular hole (Study eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Retinal aneurysm (Fellow untreated eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Retinopathy (Study eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Visual acuity reduced (Study eye)  1  1/180 (0.56%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Vitreous haemorrhage (Study eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Gastrointestinal disorders         
Diverticulum intestinal haemorrhagic  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Dyspepsia  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Gastric ulcer  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Inguinal hernia  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Intestinal polyp  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Large intestine polyp  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Hepatobiliary disorders         
Bile duct stone  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Cholelithiasis  1  2/180 (1.11%)  2/183 (1.09%)  0/63 (0.00%)  0/25 (0.00%) 
Gallbladder disorder  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Hepatic mass  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Jaundice  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Infections and infestations         
Appendicitis  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Bronchitis  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Dengue fever  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Lower respiratory tract infection  1  1/180 (0.56%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Perichondritis  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Pneumonia  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  1/25 (4.00%) 
Respiratory tract infection  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Septic shock  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Injury, poisoning and procedural complications         
Facial bones fracture (Fellow untreated eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Femur fracture  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Head injury  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Hip fracture  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Lumbar vertebral fracture  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Pelvic fracture  1  1/180 (0.56%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Periprosthetic fracture  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Investigations         
Intraocular pressure increased (Fellow untreated eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Intraocular pressure increased (Study eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Metabolism and nutrition disorders         
Hyperkalaemia  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Hyponatraemia  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Intervertebral disc protrusion  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Osteoarthritis  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma of colon  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Basal cell carcinoma  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Colorectal cancer  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Gastrointestinal carcinoma  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Lung neoplasm malignant  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Prostate cancer  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Thyroid cancer  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Nervous system disorders         
Amnesia  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Basal ganglia stroke  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Cerebrovascular accident  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Dizziness  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Dysarthria  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Headache  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Ischaemic stroke  1  1/180 (0.56%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Syncope  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Transient ischaemic attack  1  0/180 (0.00%)  1/183 (0.55%)  1/63 (1.59%)  0/25 (0.00%) 
Psychiatric disorders         
Anxiety  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Burnout syndrome  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Depression  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Renal and urinary disorders         
Prerenal failure  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Renal failure chronic  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Urethral stenosis  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Reproductive system and breast disorders         
Benign prostatic hyperplasia  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Ovarian cyst  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute respiratory failure  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Dyspnoea  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  0/25 (0.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis bullous  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Vascular disorders         
Aortic aneurysm  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Hypertension  1  1/180 (0.56%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Hypovolaemic shock  1  0/180 (0.00%)  0/183 (0.00%)  1/63 (1.59%)  0/25 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Ranibizumab 0.5mg Ranibizumab 0.5mg + Laser Laser Monotherapy With Ranibizumab 0.5 mg From Month 6 Laser Monotherapy Without Ranibizumab 0.5 mg From Month 6
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   112/180 (62.22%)   121/183 (66.12%)   40/63 (63.49%)   14/25 (56.00%) 
Ear and labyrinth disorders         
Vertigo  1  3/180 (1.67%)  1/183 (0.55%)  2/63 (3.17%)  0/25 (0.00%) 
Eye disorders         
Blepharitis (Fellow untreated eye)  1  2/180 (1.11%)  11/183 (6.01%)  0/63 (0.00%)  0/25 (0.00%) 
Blepharitis (Study eye)  1  3/180 (1.67%)  11/183 (6.01%)  1/63 (1.59%)  0/25 (0.00%) 
Cataract (Fellow untreated eye)  1  3/180 (1.67%)  6/183 (3.28%)  0/63 (0.00%)  0/25 (0.00%) 
Cataract (Study eye)  1  8/180 (4.44%)  3/183 (1.64%)  1/63 (1.59%)  0/25 (0.00%) 
Conjunctival haemorrhage (Study eye)  1  15/180 (8.33%)  15/183 (8.20%)  5/63 (7.94%)  0/25 (0.00%) 
Conjunctivitis allergic (Study eye)  1  5/180 (2.78%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Corneal erosion (Study eye)  1  0/180 (0.00%)  4/183 (2.19%)  0/63 (0.00%)  0/25 (0.00%) 
Cystoid macular oedema (Study eye)  1  4/180 (2.22%)  1/183 (0.55%)  1/63 (1.59%)  0/25 (0.00%) 
Dry eye (Fellow untreated eye)  1  9/180 (5.00%)  3/183 (1.64%)  2/63 (3.17%)  0/25 (0.00%) 
Dry eye (Study eye)  1  10/180 (5.56%)  3/183 (1.64%)  2/63 (3.17%)  0/25 (0.00%) 
Eye irritation (Study eye)  1  4/180 (2.22%)  7/183 (3.83%)  1/63 (1.59%)  0/25 (0.00%) 
Eye pain (Study eye)  1  18/180 (10.00%)  21/183 (11.48%)  3/63 (4.76%)  0/25 (0.00%) 
Eye pruritus (Study eye)  1  4/180 (2.22%)  2/183 (1.09%)  2/63 (3.17%)  0/25 (0.00%) 
Eyelid oedema (Study eye)  1  4/180 (2.22%)  3/183 (1.64%)  0/63 (0.00%)  0/25 (0.00%) 
Glaucoma (Study eye)  1  4/180 (2.22%)  2/183 (1.09%)  0/63 (0.00%)  0/25 (0.00%) 
Lacrimation increased (Study eye)  1  5/180 (2.78%)  2/183 (1.09%)  1/63 (1.59%)  0/25 (0.00%) 
Macular fibrosis (Study eye)  1  8/180 (4.44%)  7/183 (3.83%)  1/63 (1.59%)  0/25 (0.00%) 
Macular oedema (Study eye)  1  4/180 (2.22%)  5/183 (2.73%)  3/63 (4.76%)  1/25 (4.00%) 
Metamorphopsia (Study eye)  1  1/180 (0.56%)  0/183 (0.00%)  2/63 (3.17%)  0/25 (0.00%) 
Ocular hyperaemia (Study eye)  1  7/180 (3.89%)  8/183 (4.37%)  0/63 (0.00%)  0/25 (0.00%) 
Ocular hypertension (Fellow untreated eye)  1  3/180 (1.67%)  4/183 (2.19%)  1/63 (1.59%)  1/25 (4.00%) 
Ocular hypertension (Study eye)  1  5/180 (2.78%)  4/183 (2.19%)  0/63 (0.00%)  2/25 (8.00%) 
Photopsia (Study eye)  1  2/180 (1.11%)  2/183 (1.09%)  2/63 (3.17%)  0/25 (0.00%) 
Posterior capsule opacification (Study eye)  1  2/180 (1.11%)  0/183 (0.00%)  2/63 (3.17%)  0/25 (0.00%) 
Punctate keratitis (Study eye)  1  6/180 (3.33%)  1/183 (0.55%)  1/63 (1.59%)  0/25 (0.00%) 
Retinal haemorrhage (Study eye)  1  5/180 (2.78%)  3/183 (1.64%)  2/63 (3.17%)  1/25 (4.00%) 
Retinal ischaemia (Study eye)  1  2/180 (1.11%)  4/183 (2.19%)  1/63 (1.59%)  0/25 (0.00%) 
Retinal neovascularisation (Study eye)  1  2/180 (1.11%)  1/183 (0.55%)  1/63 (1.59%)  1/25 (4.00%) 
Retinal vein occlusion (Study eye)  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  1/25 (4.00%) 
Vision blurred (Study eye)  1  1/180 (0.56%)  6/183 (3.28%)  0/63 (0.00%)  0/25 (0.00%) 
Visual acuity reduced (Study eye)  1  5/180 (2.78%)  6/183 (3.28%)  4/63 (6.35%)  1/25 (4.00%) 
Vitreous adhesions (Study eye)  1  1/180 (0.56%)  2/183 (1.09%)  2/63 (3.17%)  0/25 (0.00%) 
Vitreous detachment (Study eye)  1  8/180 (4.44%)  7/183 (3.83%)  1/63 (1.59%)  0/25 (0.00%) 
Vitreous floaters (Study eye)  1  7/180 (3.89%)  10/183 (5.46%)  4/63 (6.35%)  1/25 (4.00%) 
Vitreous haemorrhage (Study eye)  1  5/180 (2.78%)  6/183 (3.28%)  1/63 (1.59%)  0/25 (0.00%) 
Gastrointestinal disorders         
Diarrhoea  1  5/180 (2.78%)  2/183 (1.09%)  3/63 (4.76%)  0/25 (0.00%) 
Gastrooesophageal reflux disease  1  1/180 (0.56%)  8/183 (4.37%)  0/63 (0.00%)  0/25 (0.00%) 
Gingival bleeding  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Nausea  1  2/180 (1.11%)  2/183 (1.09%)  2/63 (3.17%)  0/25 (0.00%) 
Toothache  1  0/180 (0.00%)  0/183 (0.00%)  2/63 (3.17%)  0/25 (0.00%) 
Vomiting  1  3/180 (1.67%)  2/183 (1.09%)  2/63 (3.17%)  0/25 (0.00%) 
General disorders         
Oedema peripheral  1  6/180 (3.33%)  2/183 (1.09%)  2/63 (3.17%)  0/25 (0.00%) 
Infections and infestations         
Acute sinusitis  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Bronchitis  1  3/180 (1.67%)  1/183 (0.55%)  1/63 (1.59%)  1/25 (4.00%) 
Conjunctivitis (Fellow untreated eye)  1  1/180 (0.56%)  5/183 (2.73%)  1/63 (1.59%)  0/25 (0.00%) 
Conjunctivitis (Study eye)  1  1/180 (0.56%)  4/183 (2.19%)  1/63 (1.59%)  0/25 (0.00%) 
Herpes zoster  1  2/180 (1.11%)  4/183 (2.19%)  1/63 (1.59%)  0/25 (0.00%) 
Influenza  1  13/180 (7.22%)  13/183 (7.10%)  2/63 (3.17%)  1/25 (4.00%) 
Laryngitis  1  2/180 (1.11%)  0/183 (0.00%)  1/63 (1.59%)  1/25 (4.00%) 
Nasopharyngitis  1  15/180 (8.33%)  17/183 (9.29%)  4/63 (6.35%)  1/25 (4.00%) 
Onychomycosis  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  1/25 (4.00%) 
Pneumonia  1  4/180 (2.22%)  2/183 (1.09%)  1/63 (1.59%)  0/25 (0.00%) 
Sinusitis  1  8/180 (4.44%)  2/183 (1.09%)  1/63 (1.59%)  0/25 (0.00%) 
Upper respiratory tract infection  1  6/180 (3.33%)  6/183 (3.28%)  3/63 (4.76%)  0/25 (0.00%) 
Urinary tract infection  1  6/180 (3.33%)  4/183 (2.19%)  3/63 (4.76%)  0/25 (0.00%) 
Injury, poisoning and procedural complications         
Contusion  1  1/180 (0.56%)  3/183 (1.64%)  1/63 (1.59%)  1/25 (4.00%) 
Fall  1  2/180 (1.11%)  6/183 (3.28%)  3/63 (4.76%)  0/25 (0.00%) 
Limb injury  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Procedural pain  1  4/180 (2.22%)  1/183 (0.55%)  0/63 (0.00%)  0/25 (0.00%) 
Upper limb fracture  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Investigations         
Blood pressure increased  1  3/180 (1.67%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Intraocular pressure increased (Study eye)  1  17/180 (9.44%)  17/183 (9.29%)  2/63 (3.17%)  0/25 (0.00%) 
Metabolism and nutrition disorders         
Diabetes mellitus  1  3/180 (1.67%)  3/183 (1.64%)  2/63 (3.17%)  0/25 (0.00%) 
Hypercholesterolaemia  1  3/180 (1.67%)  6/183 (3.28%)  0/63 (0.00%)  0/25 (0.00%) 
Hyperlipidaemia  1  2/180 (1.11%)  0/183 (0.00%)  3/63 (4.76%)  0/25 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  4/180 (2.22%)  6/183 (3.28%)  1/63 (1.59%)  0/25 (0.00%) 
Arthritis  1  2/180 (1.11%)  2/183 (1.09%)  0/63 (0.00%)  1/25 (4.00%) 
Back pain  1  5/180 (2.78%)  8/183 (4.37%)  1/63 (1.59%)  2/25 (8.00%) 
Bone pain  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Musculoskeletal pain  1  1/180 (0.56%)  5/183 (2.73%)  1/63 (1.59%)  1/25 (4.00%) 
Osteoarthritis  1  5/180 (2.78%)  8/183 (4.37%)  3/63 (4.76%)  1/25 (4.00%) 
Pain in extremity  1  4/180 (2.22%)  7/183 (3.83%)  0/63 (0.00%)  0/25 (0.00%) 
Nervous system disorders         
Dizziness  1  2/180 (1.11%)  6/183 (3.28%)  0/63 (0.00%)  1/25 (4.00%) 
Headache  1  11/180 (6.11%)  9/183 (4.92%)  6/63 (9.52%)  0/25 (0.00%) 
Migraine  1  0/180 (0.00%)  4/183 (2.19%)  1/63 (1.59%)  0/25 (0.00%) 
Presyncope  1  0/180 (0.00%)  1/183 (0.55%)  0/63 (0.00%)  1/25 (4.00%) 
Sciatica  1  0/180 (0.00%)  0/183 (0.00%)  2/63 (3.17%)  0/25 (0.00%) 
Visual field defect (Fellow untreated eye)  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Psychiatric disorders         
Depression  1  1/180 (0.56%)  4/183 (2.19%)  1/63 (1.59%)  0/25 (0.00%) 
Insomnia  1  0/180 (0.00%)  4/183 (2.19%)  0/63 (0.00%)  0/25 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  4/180 (2.22%)  6/183 (3.28%)  4/63 (6.35%)  0/25 (0.00%) 
Oropharyngeal pain  1  4/180 (2.22%)  2/183 (1.09%)  0/63 (0.00%)  0/25 (0.00%) 
Pleurisy  1  1/180 (0.56%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Skin and subcutaneous tissue disorders         
Dermatitis allergic  1  1/180 (0.56%)  0/183 (0.00%)  2/63 (3.17%)  0/25 (0.00%) 
Vascular disorders         
Hypertension  1  19/180 (10.56%)  22/183 (12.02%)  7/63 (11.11%)  2/25 (8.00%) 
Phlebitis superficial  1  0/180 (0.00%)  0/183 (0.00%)  0/63 (0.00%)  1/25 (4.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Clinical Disclosure Office
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01599650     History of Changes
Other Study ID Numbers: CRFB002E2402
2011-002859-34 ( EudraCT Number )
First Submitted: May 2, 2012
First Posted: May 16, 2012
Results First Submitted: May 26, 2016
Results First Posted: November 10, 2016
Last Update Posted: November 10, 2016