Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A 24-month, phase IIIb, open-label, randomized, active-controlled, 3-arm, multicenter study assessing the efficacy and safety of an individualized, stabilization-criteria-driven pro re nata (PRN) dosing regimen with 0.5-mg ranibizumab intravitreal injections applied as monotherapy or with adjunctive laser photocoagulation in comparison to laser photocoagulation in patients with visual impairment due to macular edema (ME) secondary to branch retinal vein occlusion (BRVO) (BRIGHTER).

    Summary
    EudraCT number
    		 2011-002859-34
    Trial protocol
    		 IE   GB   SE   HU   CZ   ES   SK   GR   NL   PT   PL   FR   IT   DK  
    Global end of trial date
    27 May 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    11 Jun 2016
    First version publication date
    11 Jun 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CRFB002E2402
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01599650
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 May 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 May 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary objective: to demonstrate that an individualized stabilization-criteria-driven PRN dosing regimen with 0.5-mg ranibizumab administered with or without adjunctive laser treatment had superior efficacy as compared to the current standard of care, laser photocoagulation, in patients with visual impairment due to ME secondary to BRVO. The primary objective was assessed by the mean best corrected visual acuity (BCVA) change at Month 6 compared to Baseline.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 May 2012
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 14
    Country: Number of subjects enrolled
    Canada: 55
    Country: Number of subjects enrolled
    Czech Republic: 30
    Country: Number of subjects enrolled
    Denmark: 8
    Country: Number of subjects enrolled
    France: 20
    Country: Number of subjects enrolled
    Greece: 36
    Country: Number of subjects enrolled
    Hungary: 18
    Country: Number of subjects enrolled
    Ireland: 8
    Country: Number of subjects enrolled
    Italy: 39
    Country: Number of subjects enrolled
    Netherlands: 12
    Country: Number of subjects enrolled
    Poland: 39
    Country: Number of subjects enrolled
    Portugal: 39
    Country: Number of subjects enrolled
    Slovakia: 36
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    Sweden: 5
    Country: Number of subjects enrolled
    Switzerland: 7
    Country: Number of subjects enrolled
    United Kingdom: 53
    Worldwide total number of subjects
    455
    EEA total number of subjects
    379
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    199
    From 65 to 84 years
    244
    85 years and over
    12

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Out of 612 patients screened, 455 were randomized on a 2:2:1 ratio to receive ranibizumab (183 patients), ranibizumab with laser (180 patients), and laser monotherapy (92 patients)

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 1-ranibizumab monotherapy
    Arm description
    		 laser therapy + Ranibizumab 0.5 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    ranibizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    0.5-mg PRN by intravitreal injections

    Arm title
    		 2-ranibizumab with laser
    Arm description
    		 Ranibizumab 0.5 mg + laser
    Arm type
    		 Experimental

    Investigational medicinal product name
    ranibizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    0.5-mg ranibizumab administered PRN by intravitreal injections

    Arm title
    		 3-laser monothery
    Arm description
    		 after 6 months, laser patients could be treated with ranibizumab
    Arm type
    		 Experimental

    Investigational medicinal product name
    ranibizumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intravitreal use
    Dosage and administration details
    after 6 months, 0.5-mg ranibizumab administered PRN by intravitreal injections

    Number of subjects in period 1
    		1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Started
    183
    180
    92
    Completed 6 mos
    174
    170
    80
    Completed
    161
    154
    65
    Not completed
    22
    26
    27
         Adverse event, serious fatal
    2
    1
    2
         Physician decision
    2
    -
    7
         Consent withdrawn by subject
    11
    11
    10
         Adverse event, non-fatal
    3
    8
    4
         Administrative issue
    1
    -
    1
         Lost to follow-up
    3
    3
    3
         Protocol deviation
    -
    3
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    1-ranibizumab monotherapy
    Reporting group description
    		 laser therapy + Ranibizumab 0.5 mg

    Reporting group title
    2-ranibizumab with laser
    Reporting group description
    		 Ranibizumab 0.5 mg + laser

    Reporting group title
    3-laser monothery
    Reporting group description
    		 after 6 months, laser patients could be treated with ranibizumab

    Reporting group values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery Total
    Number of subjects
    		 183 180 92 455
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 90 71 38 199
        From 65-84 years
    		 91 104 49 244
        85 years and over
    		 2 5 5 12
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.7 ± 10.34 67.3 ± 10.41 67.7 ± 9.67 -
    Gender, Male/Female
    Units: participants
        Female
    		 90 84 55 229
        Male
    		 93 96 37 226

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    1-ranibizumab monotherapy
    Reporting group description
    		 laser therapy + Ranibizumab 0.5 mg

    Reporting group title
    2-ranibizumab with laser
    Reporting group description
    		 Ranibizumab 0.5 mg + laser

    Reporting group title
    3-laser monothery
    Reporting group description
    		 after 6 months, laser patients could be treated with ranibizumab

    Primary: 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)

    		 Close Top of page
    End point 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)
    End point 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.
    End point type
    Primary
    End point timeframe
    Baseline, 6 Months
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: letters
    arithmetic mean (standard deviation)
        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 at Month 6
    14.8 ± 10.7
    14.8 ± 11.13
    6 ± 14.27
    Statistical analysis title
    		 Group 1 vs Group 3
    Comparison groups
    1-ranibizumab monotherapy v 3-laser monothery
    Number of subjects included in analysis
    270
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 difference in LS mean
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.3
         upper limit
    		 12.8
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.41
    Statistical analysis title
    		 Group 2 vs Group 3
    Comparison groups
    2-ranibizumab with laser v 3-laser monothery
    Number of subjects included in analysis
    268
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANOVA
    Parameter type
    		 difference in LS Means
    Point estimate
    8.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.8
         upper limit
    		 11.6
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.46

    Secondary: The mean average change in visual acuity from Month 1 through Month 24 compared to Baseline

    		 Close Top of page
    End point title
    		 The mean average change in visual acuity from Month 1 through Month 24 compared to Baseline
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, 24 Months
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: letters
    arithmetic mean (standard deviation)
        Baseline
    59.5 ± 11.78
    56.6 ± 13.19
    56.8 ± 13.86
        Average Month 1 to Month 24
    74.5 ± 12.11
    72 ± 13.56
    65.9 ± 13.24
        Change from Baseline
    15 ± 10.86
    15.4 ± 10.76
    9.1 ± 13.49
    No statistical analyses for this end point

    Secondary: Number of ranibizumab treatments from Day 1 to Month 23 by treatment group

    		 Close Top of page
    End point title
    		 Number of ranibizumab treatments from Day 1 to Month 23 by treatment group [1]
    End point description
    Number of injections provided to the patients during the 23 month period and conducted within FAS with LOCF and observed data.
    End point type
    Secondary
    End point timeframe
    Day 1 through Month 23
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: provide output for primary endpoints only
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser
    Number of subjects analysed
    180
    178
    Units: treatments
        arithmetic mean (standard deviation)
    11.4 ± 5.76
    11.3 ± 6.03
    No statistical analyses for this end point

    Secondary: Mean average change in visual acuity (BCVA letters) from Month 1 through Month 6

    		 Close Top of page
    End point title
    		 Mean average change in visual acuity (BCVA letters) from Month 1 through Month 6
    End point 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.
    End point type
    Secondary
    End point timeframe
    From Baseline through Month 6
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: BCVA
    arithmetic mean (standard deviation)
        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 ± 9.6
    13.2 ± 9.89
    4.8 ± 11.69
    No statistical analyses for this end point

    Secondary: The mean change in visual acuity BCVA (letters) from Baseline at Month 12 and Month 24

    		 Close Top of page
    End point title
    		 The mean change in visual acuity BCVA (letters) from Baseline at Month 12 and Month 24
    End point 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.
    End point type
    Secondary
    End point timeframe
    Baseline, Month 12 and Month 24
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: letters
    arithmetic mean (standard deviation)
        Baseline
    59.5 ± 11.78
    56.6 ± 13.19
    56.8 ± 13.78
        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 ± 14.33
        Month 24
    75 ± 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
    No statistical analyses for this end point

    Secondary: 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

    		 Close Top of page
    End point 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
    End point 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).
    End point type
    Secondary
    End point timeframe
    Baseline, Month 6 and Month 24
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: percent gaining improvement
    number (not applicable)
        BCVA improvement of >= 1 letter month 6
    93.3
    96.1
    63.3
        BCVA improvement of >= 1 letter month 24
    89.4
    93.8
    77.8
        BCVA improvement of >= 5 letters month 6
    86.1
    88.2
    50
        BCVA improvement of >= 5 letters month 24
    83.3
    89.3
    70
        BCVA improvement of >= 10 letters month 6
    66.7
    68.5
    41.1
        BCVA improvement of >= 10 letters month 24
    71.1
    75.8
    60
        BCVA improvement of >= 15 letters month 6
    45
    47.2
    27.8
        BCVA improvement of >= 15 letters month 24
    52.8
    59.6
    43.3
        BCVA improvement of >= 30 letters month 6
    10
    9.6
    3.3
        BCVA improvement of >= 30 letters month 24
    13.3
    14
    11.1
    No statistical analyses for this end point

    Secondary: BCVA (letters) number and proportion of patients with a BCVA improvement vs Baseline or achieving greater than or equal to 73 letters at Month 6 in the study eye

    		 Close Top of page
    End point title
    		 BCVA (letters) number and proportion of patients with a BCVA improvement vs Baseline or achieving greater than or equal to 73 letters at Month 6 in the study eye
    End point 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.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: 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
    No statistical analyses for this end point

    Secondary: BCVA (letters) number and proportion of patients with a BCVA improvement vs Baseline or achieved greater than or equal to 73 letters at Month 24 in the study eye

    		 Close Top of page
    End point title
    		 BCVA (letters) number and proportion of patients with a BCVA improvement vs Baseline or achieved greater than or equal to 73 letters at Month 24 in the study eye
    End point 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.
    End point type
    Secondary
    End point timeframe
    Month 24
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: 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
    No statistical analyses for this end point

    Secondary: Evaluate the mean change in central reading center-assessed central subfield thickness from Month 12 and Month 24 compared to Baseline by treatment arm

    		 Close Top of page
    End point title
    		 Evaluate the mean change in central reading center-assessed central subfield thickness from Month 12 and Month 24 compared to Baseline by treatment arm
    End point 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)
    End point type
    Secondary
    End point timeframe
    Month 12 and Month 24
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: microns
    arithmetic mean (standard error)
        month 12
    -215.9 ± 12.83
    -242.5 ± 14.14
    -203.9 ± 22.22
        month 24
    -228.1 ± 12.65
    -261.7 ± 15.2
    -232.7 ± 24.38
    No statistical analyses for this end point

    Secondary: 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

    		 Close Top of page
    End point 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
    End point 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. The score of each individual question ranges from 0 (worst) to 100 which indicates the best possible response. The composite score and score of each of each construct also range from 0 to 100 as they are calculated as total scores divided by the number of questions. Scores per visit and of the change descriptively by visit.
    End point type
    Secondary
    End point timeframe
    Months 6 and 24
    End point values
    		 1-ranibizumab monotherapy 2-ranibizumab with laser 3-laser monothery
    Number of subjects analysed
    180
    178
    90
    Units: score on a scale
    arithmetic mean (standard deviation)
        month 6 composite score
    5.6 ± 9.56
    4.2 ± 10.41
    3.7 ± 12.12
        month 24 composite score
    8 ± 11.78
    5 ± 11.44
    4.9 ± 14.79
    No statistical analyses for this end point

    Secondary: BCVA (letters) mean average change from first ranibizumab treatment to Month 24 in the study eye for patients randomized to the laser monotherapy arm

    		 Close Top of page
    End point 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 [2]
    End point 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.
    End point type
    Secondary
    End point timeframe
    Month 24
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: provide output for primary endpoints only
    End point values
    		 3-laser monothery
    Number of subjects analysed
    66 [3]
    Units: BCVA letters
    arithmetic mean (standard deviation)
        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
    Notes
    [3] - Laser monotherapy with Ranibizumab 0.5 mg from Month 6
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Ranibizumab 0.5 mg
    Reporting group description
    		 Ranibizumab 0.5 mg

    Reporting group title
    Ranibizumab 0.5 mg + laser
    Reporting group description
    		 Ranibizumab 0.5 mg + laser

    Reporting group title
    Laser monotherapy with Ranibizumab 0.5 mg from Month 6
    Reporting group description
    		 Laser monotherapy with Ranibizumab 0.5 mg from Month 6

    Reporting group title
    Laser monotherapy without Ranibizumab 0.5 mg from Month 6
    Reporting group description
    		 Laser monotherapy without Ranibizumab 0.5 mg from Month 6

    Serious adverse events
    		 Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser Laser monotherapy with Ranibizumab 0.5 mg from Month 6 Laser monotherapy without Ranibizumab 0.5 mg from Month 6
    Total subjects affected by serious adverse events
         subjects affected / exposed
    30 / 180 (16.67%)
    33 / 183 (18.03%)
    10 / 63 (15.87%)
    3 / 25 (12.00%)
         number of deaths (all causes)
    2
    1
    2
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colorectal cancer
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid cancer
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic aneurysm
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Burnout syndrome
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Intraocular pressure increased (Fellow untreated eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intraocular pressure increased (Study eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Facial bones fracture (Fellow untreated eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pelvic fracture
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Periprosthetic fracture
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aortic valve incompetence
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 180 (1.67%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery embolism
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial ischaemia
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Amnesia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Basal ganglia stroke
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract (Fellow untreated eye)
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cataract (Study eye)
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular fibrosis (Study eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Macular hole (Study eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinal aneurysm (Fellow untreated eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Retinopathy (Study eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Visual acuity reduced (Study eye)
         subjects affected / exposed
    1 / 180 (0.56%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage (Study eye)
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diverticulum intestinal haemorrhagic
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    2 / 180 (1.11%)
    2 / 183 (1.09%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gallbladder disorder
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic mass
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis bullous
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Prerenal failure
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urethral stenosis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Perichondritis
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 180 (0.00%)
    1 / 183 (0.55%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    0 / 180 (0.00%)
    0 / 183 (0.00%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 180 (0.56%)
    0 / 183 (0.00%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ranibizumab 0.5 mg Ranibizumab 0.5 mg + laser Laser monotherapy with Ranibizumab 0.5 mg from Month 6 Laser monotherapy without Ranibizumab 0.5 mg from Month 6
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    74 / 180 (41.11%)
    88 / 183 (48.09%)
    28 / 63 (44.44%)
    8 / 25 (32.00%)
    Investigations
    Intraocular pressure increased (Study eye)
         subjects affected / exposed
    17 / 180 (9.44%)
    17 / 183 (9.29%)
    2 / 63 (3.17%)
    0 / 25 (0.00%)
         occurrences all number
    30
    33
    2
    0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    19 / 180 (10.56%)
    22 / 183 (12.02%)
    7 / 63 (11.11%)
    2 / 25 (8.00%)
         occurrences all number
    23
    22
    8
    2
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 180 (6.11%)
    9 / 183 (4.92%)
    6 / 63 (9.52%)
    0 / 25 (0.00%)
         occurrences all number
    21
    19
    12
    0
    Eye disorders
    Blepharitis (Fellow untreated eye)
         subjects affected / exposed
    2 / 180 (1.11%)
    11 / 183 (6.01%)
    0 / 63 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    2
    11
    0
    0
    Blepharitis (Study eye)
         subjects affected / exposed
    3 / 180 (1.67%)
    11 / 183 (6.01%)
    1 / 63 (1.59%)
    0 / 25 (0.00%)
         occurrences all number
    3
    11
    1
    0
    Conjunctival haemorrhage (Study eye)
         subjects affected / exposed
    15 / 180 (8.33%)
    15 / 183 (8.20%)
    5 / 63 (7.94%)
    0 / 25 (0.00%)
         occurrences all number
    27
    26
    8
    0
    Dry eye (Fellow untreated eye)
         subjects affected / exposed
    9 / 180 (5.00%)
    3 / 183 (1.64%)
    2 / 63 (3.17%)
    0 / 25 (0.00%)
         occurrences all number
    10
    3
    2
    0
    Dry eye (Study eye)
         subjects affected / exposed
    10 / 180 (5.56%)
    3 / 183 (1.64%)
    2 / 63 (3.17%)
    0 / 25 (0.00%)
         occurrences all number
    11
    3
    2
    0
    Eye pain (Study eye)
         subjects affected / exposed
    18 / 180 (10.00%)
    21 / 183 (11.48%)
    3 / 63 (4.76%)
    0 / 25 (0.00%)
         occurrences all number
    28
    29
    3
    0
    Ocular hypertension (Study eye)
         subjects affected / exposed
    5 / 180 (2.78%)
    4 / 183 (2.19%)
    0 / 63 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    5
    4
    0
    2
    Visual acuity reduced (Study eye)
         subjects affected / exposed
    5 / 180 (2.78%)
    6 / 183 (3.28%)
    4 / 63 (6.35%)
    1 / 25 (4.00%)
         occurrences all number
    6
    6
    4
    1
    Vitreous floaters (Study eye)
         subjects affected / exposed
    7 / 180 (3.89%)
    10 / 183 (5.46%)
    4 / 63 (6.35%)
    1 / 25 (4.00%)
         occurrences all number
    7
    11
    4
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 180 (2.22%)
    6 / 183 (3.28%)
    4 / 63 (6.35%)
    0 / 25 (0.00%)
         occurrences all number
    4
    7
    4
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 180 (2.78%)
    8 / 183 (4.37%)
    1 / 63 (1.59%)
    2 / 25 (8.00%)
         occurrences all number
    5
    8
    1
    2
    Infections and infestations
    Influenza
         subjects affected / exposed
    13 / 180 (7.22%)
    13 / 183 (7.10%)
    2 / 63 (3.17%)
    1 / 25 (4.00%)
         occurrences all number
    17
    17
    2
    1
    Nasopharyngitis
         subjects affected / exposed
    15 / 180 (8.33%)
    17 / 183 (9.29%)
    4 / 63 (6.35%)
    1 / 25 (4.00%)
         occurrences all number
    18
    25
    5
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri May 03 03:30:47 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA