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Ranibizumab and Bevacizumab for Diabetic Macular Edema

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ClinicalTrials.gov Identifier: NCT01610557
Recruitment Status : Completed
First Posted : June 4, 2012
Results First Posted : April 27, 2016
Last Update Posted : August 19, 2016
Sponsor:
Collaborator:
The EMMES Corporation
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Diabetic Macular Edema
Interventions Drug: Ranibizumab
Drug: Bevacizumab
Enrollment 56
Recruitment Details  
Pre-assignment Details 56 participants enrolled: 50 participants had one eye randomly assigned (unilateral participants) and 6 participants had two eyes enrolled (bilateral participants) for a total of 62 eyes analyzed at baseline. Bilateral participants had the right eye randomly assigned; the left eye assigned to the group with the schedule inverse to the right eye.
Arm/Group Title Group 1 - Ranibizumab-Ranibizumab-Bevacizumab Injection Series Group 2 - Ranibizumab-Bevacizumab-Bevacizumab Injection Series Group 3 - Bevacizumab-Bevacizumab-Ranibizumab Injection Series Group 4 - Bevacizumab-Ranibizumab-Ranibizumab Injection Series Ranibizumab/Bevacizumab As Needed
Hide Arm/Group Description

Group 1 eyes were assigned to Ranibizumab-Ranibizumab-Bevacizumab (RRB) treatment sequence and received intravitreal injections of ranibizumab at baseline, Weeks 4, and 8 (period 1), and Weeks 12, 16 and 20 (period 2), then crossed over to receive intravitreal injections of bevacizumab at Weeks 24, 28 and 32 (period 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 2 eyes were assigned to Ranibizumab-Bevacizumab-Bevacizumab (RBB) treatment sequence and received intravitreal injections of ranibizumab at baseline and Weeks 4 and 8 (period 1), then crossed over to receive intravitreal injections of bevacizumab at Weeks 12, 16, 20, 24, 28 and 32 (periods 2 and 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 3 eyes were assigned to Bevacizumab-Bevacizumab-Ranibizumab (BBR) treatment sequence and received intravitreal injections of bevacizumab at baseline and Weeks 4, 8, 12, 16 and 20 (periods 1 and 2), then crossed over to receive intravitreal injections of ranibizumab at Weeks 24, 28 and 32 (period 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 4 eyes were assigned to Bevacizumab-Ranibizumab-Ranibizumab (BRR) treatment sequence and received intravitreal injections of bevacizumab at baseline and Weeks 4 and 8 (period 1), then crossed over to receive intravitreal injections of ranibizumab at Weeks 12, 16, 20, 24, 28 and 32 (periods 2 and 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Post-36-Week Extension Phase: Eyes assigned to Group 1 or Group 2 in the crossover phase were injected with ranibizumab on an as-needed basis. Eyes assigned to Group 3 or Group 4 in the crossover phase were injected with bevacizumab on an as-needed basis.

53 participants attended at least one follow-up visit in the post-36-week extension phase: 49 participants who had one eye enrolled and 4 participants who had two eyes enrolled.

Period Title: 36-Week Randomized Crossover Phase
Started 16 [1] 13 [2] 14 [3] 13 [4] 0 [5]
Completed 16 12 [6] 14 13 0 [5]
Not Completed 0 1 0 0 0
Reason Not Completed
Withdrawal by Subject             0             1             0             0             0
[1]
Participants randomly assigned to Grp 1: 14 unilateral and 2 bilateral (left eye assigned to Grp 3)
[2]
Participants randomly assigned to Grp 2: 12 unilateral and 1 bilateral (left eye assigned to Grp 4)
[3]
Participants randomly assigned to Grp 3: 13 unilateral and 1 bilateral (left eye assigned to Grp 1)
[4]
Participants randomly assigned to Grp 4: 11 unilateral and 2 bilateral (left eye assigned to Grp 2)
[5]
Not applicable for 36-week double-masked randomized crossover phase
[6]
Unilateral participant unable to return for visits after Wk 4 due to recovery from an adverse event
Period Title: Post-36-Week Extension Phase
Started 0 [1] 0 [1] 0 [1] 0 [1] 55
Completed 0 [1] 0 [1] 0 [1] 0 [1] 52 [2]
Not Completed 0 0 0 0 3
Reason Not Completed
Withdrawal by Subject             0             0             0             0             3
[1]
Not applicable for the post-36-week extension phase
[2]
2 bilateral participants withdrew before their first post-36-week extension visit
Arm/Group Title Group 1 - Ranibizumab-Ranibizumab-Bevacizumab Injection Series Group 2 - Ranibizumab-Bevacizumab-Bevacizumab Injection Series Group 3 - Bevacizumab-Bevacizumab-Ranibizumab Injection Series Group 4 - Bevacizumab-Ranibizumab-Ranibizumab Injection Series Total
Hide Arm/Group Description

Group 1 eyes were assigned to Ranibizumab-Ranibizumab-Bevacizumab (RRB) treatment sequence and received intravitreal injections of ranibizumab at baseline, Weeks 4, and 8 (period 1), and Weeks 12, 16 and 20 (period 2), then crossed over to receive intravitreal injections of bevacizumab at Weeks 24, 28 and 32 (period 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 2 eyes were assigned to Ranibizumab-Bevacizumab-Bevacizumab (RBB) treatment sequence and received intravitreal injections of ranibizumab at baseline and Weeks 4 and 8 (period 1), then crossed over to receive intravitreal injections of bevacizumab at Weeks 12, 16, 20, 24, 28 and 32 (periods 2 and 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 3 eyes were assigned to Bevacizumab-Bevacizumab-Ranibizumab (BBR) treatment sequence and received intravitreal injections of bevacizumab at baseline and Weeks 4, 8, 12, 16 and 20 (periods 1 and 2), then crossed over to receive intravitreal injections of ranibizumab at Weeks 24, 28 and 32 (period 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 4 eyes were assigned to Bevacizumab-Ranibizumab-Ranibizumab (BRR) treatment sequence and received intravitreal injections of bevacizumab at baseline and Weeks 4 and 8 (period 1), then crossed over to receive intravitreal injections of ranibizumab at Weeks 12, 16, 20, 24, 28 and 32 (periods 2 and 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Total of all reporting groups
Overall Number of Baseline Participants 17 15 16 14 62
Hide Baseline Analysis Population Description
Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.
Age, Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
62.4
(39 to 85)
65.9
(39 to 87)
62.3
(39 to 83)
61.8
(51 to 82)
63
(39 to 87)
[1]
Measure Description: Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
Female
4
  23.5%
8
  53.3%
7
  43.8%
5
  35.7%
24
  38.7%
Male
13
  76.5%
7
  46.7%
9
  56.3%
9
  64.3%
38
  61.3%
[1]
Measure Description: Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
Hispanic or Latino
2
  11.8%
0
   0.0%
1
   6.3%
0
   0.0%
3
   4.8%
Not Hispanic or Latino
15
  88.2%
15
 100.0%
14
  87.5%
14
 100.0%
58
  93.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   6.3%
0
   0.0%
1
   1.6%
[1]
Measure Description: Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   5.9%
0
   0.0%
1
   6.3%
1
   7.1%
3
   4.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
2
  11.8%
2
  13.3%
2
  12.5%
2
  14.3%
8
  12.9%
White
12
  70.6%
13
  86.7%
11
  68.8%
10
  71.4%
46
  74.2%
More than one race
1
   5.9%
0
   0.0%
2
  12.5%
0
   0.0%
3
   4.8%
Unknown or Not Reported
1
   5.9%
0
   0.0%
0
   0.0%
1
   7.1%
2
   3.2%
[1]
Measure Description: Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes
Diabetes Type   [1] 
Measure Type: Number
Unit of measure:  Eyes
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
Diabetes Type 1 2 2 1 2 7
Diabetes Type 2 15 13 15 12 55
[1]
Measure Description: Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes
Hemoglobin A1C (%)   [1] 
Mean (Full Range)
Unit of measure:  Percentage of glycosylated hemoglobin
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
8.1
(6.2 to 11.5)
8.4
(5.8 to 12.2)
7.9
(6.2 to 10.6)
7.8
(5.8 to 10.3)
8.1
(5.8 to 12.2)
[1]
Measure Description: Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.
Best-corrected visual acuity   [1] 
Mean (Full Range)
Unit of measure:  ETDRS letters
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
65
(38 to 78)
61
(32 to 73)
65
(44 to 75)
65
(50 to 78)
64
(32 to 78)
[1]
Measure Description:

Best-corrected visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS chart.

Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.

Optical Coherence Tomography (OCT) Central Subfield Mean Thickness   [1] 
Mean (Full Range)
Unit of measure:  Micrometers
Number Analyzed 17 participants 15 participants 16 participants 14 participants 62 participants
484
(334 to 720)
444
(366 to 602)
471
(362 to 606)
508
(358 to 653)
477
(334 to 720)
[1]
Measure Description:

Participants with both eyes enrolled are counted twice (by eye), once for each of the treatment sequences to which an eye was assigned randomly. Although 56 participants enrolled, 6 participants had two eyes enrolled for a total of 62 eyes.

Optical Coherence Tomography (OCT) scans were masked and graded at an external reading center (Duke University, Durham, North Carolina).

1.Primary Outcome
Title Mean Change in Early Treatment Diabetic Retinopathy Study (ETDRS) Best-corrected Visual Acuity (BCVA) From Baseline to 36 Weeks (Crossover Phase of the Study)
Hide Description

The primary outcome for 3-months change in BCVA utilized data from Weeks 12, 24 and 36 aggregated in a linear mixed-effects model. This model included adjustments accounting for period (i.e., Weeks 12, 24 and 36), treatment in current period, treatment in prior period, and baseline BCVA to provide the estimated 3-month BCVA change.

Visual acuity was measured using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Acuity is measured as letters read on an ETDRS eye chart and the letters read equate to Snellen measurements. For example, if a participant reads between 84 and 88 letters, the equivalent Snellen measurement is 20/20.

Time Frame Baseline and 36 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 56 participants (62 eyes) were enrolled and 55 participants (61 eyes) completed the 36-week crossover phase of the study.
Arm/Group Title Bevacizumab Ranibizumab
Hide Arm/Group Description:
Represents the estimated effect of bevacizumab for a 3-month period, adjusted for period and baseline value.
Represents the estimated effect of ranibizumab for a 3-month period, adjusted for period and baseline value.
Overall Number of Participants Analyzed 55 55
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
61 61
Mean (95% Confidence Interval)
Unit of Measure: ETDRS letters
5.3
(3.2 to 7.4)
6.6
(4.5 to 8.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab, Ranibizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.039
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.07 to 2.5
Estimation Comments The difference represents the estimated difference between ranibizumab and bevacizumab, adjusted for baseline visual acuity, study period, and clinical site and a subject effect for eyes nested within subject.
2.Secondary Outcome
Title Change in Central Retinal Thickness Assessed by Optical Coherence Tomography (OCT) Central Subfield Mean Thickness (CSMT) From Baseline to 36 Weeks (Crossover Phase of the Study)
Hide Description Optical Coherence Tomography (OCT) scans were graded in masked fashion by Duke University Reading Center (Durham, North Carolina). Per the initial protocol specifications, OCT scans were to be performed on a Cirrus OCT machine; however, some scans were performed on a Spectralis OCT machine at one of the sites due to technical difficulties. The protocol was amended to allow for Cirrus and Spectralis OCT scans at subsequent visits at the affected site. Spectralis values were then converted to Cirrus central subfield mean thickness (CSMT) values through a validated linear conversion function.
Time Frame Baseline and 36 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
A total of 56 participants (62 eyes) were enrolled and 55 participants (61 eyes) completed the 36-week crossover phase of the study.
Arm/Group Title Bevacizumab Ranibizumab
Hide Arm/Group Description:
Represents the estimated effect of bevacizumab for a 3-month period, adjusted for period and baseline value.
Represents the estimated effect of ranibizumab for a 3-month period, adjusted for period and baseline value.
Overall Number of Participants Analyzed 55 55
Overall Number of Units Analyzed
Type of Units Analyzed: Eyes
61 61
Mean (95% Confidence Interval)
Unit of Measure: micrometers
-89
(-116 to -62)
-137
(-164 to -110)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bevacizumab, Ranibizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -48
Confidence Interval (2-Sided) 95%
-65 to -31
Estimation Comments The difference represents the estimated difference between ranibizumab and bevacizumab, adjusted for baseline visual acuity, study period, and clinical site and a subject effect for eyes nested within subject.
Time Frame Data were collected from 56 participants randomly-assigned to Groups 1 through 4 during the 36-week crossover period. After 36 weeks, data were collected from 53 participants who completed at least one post-36-week visit.
Adverse Event Reporting Description 36-week crossover period:Of the 56 participants, 50 had one eye and 6 had two eyes enrolled; data collected from the 6 participants with two eyes enrolled are reflected in the group to which the participant's right eye was randomly assigned. Post-36-weeks:Of the 53 participants, data were collected from 49 with one eye and 4 with two eyes enrolled.
 
Arm/Group Title Group 1 - Ranibizumab-Ranibizumab-Bevacizumab Injection Series Group 2 - Ranibizumab-Bevacizumab-Bevacizumab Injection Series Group 3 - Bevacizumab-Bevacizumab-Ranibizumab Injection Series Group 4 - Bevacizumab-Ranibizumab-Ranibizumab Injection Series Ranibizumab As Needed (Post-36-Week Extension) Bevacizumab As Needed (Post-36-Week Extension) Ranibizumab and Bevacizumab As Needed (Post-36-Week Extension)
Hide Arm/Group Description

Group 1 eyes were assigned to Ranibizumab-Ranibizumab-Bevacizumab (RRB) treatment sequence and received intravitreal injections of ranibizumab at baseline, Weeks 4, and 8 (period 1), and Weeks 12, 16 and 20 (period 2), then crossed over to receive intravitreal injections of bevacizumab at Weeks 24, 28 and 32 (period 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 2 eyes were assigned to Ranibizumab-Bevacizumab-Bevacizumab (RBB) treatment sequence and received intravitreal injections of ranibizumab at baseline and Weeks 4 and 8 (period 1), then crossed over to receive intravitreal injections of bevacizumab at Weeks 12, 16, 20, 24, 28 and 32 (periods 2 and 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 3 eyes were assigned to Bevacizumab-Bevacizumab-Ranibizumab (BBR) treatment sequence and received intravitreal injections of bevacizumab at baseline and Weeks 4, 8, 12, 16 and 20 (periods 1 and 2), then crossed over to receive intravitreal injections of ranibizumab at Weeks 24, 28 and 32 (period 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Group 4 eyes were assigned to Bevacizumab-Ranibizumab-Ranibizumab (BRR) treatment sequence and received intravitreal injections of bevacizumab at baseline and Weeks 4 and 8 (period 1), then crossed over to receive intravitreal injections of ranibizumab at Weeks 12, 16, 20, 24, 28 and 32 (periods 2 and 3).

Participants for whom one eye was enrolled in the study had this eye randomly assigned to one of four groups. Participants for whom both eyes were enrolled had the right eye randomly assigned; the left eye was assigned to the group with the schedule inverse to that for the right eye.

Post-36-Week Extension Phase: Eyes assigned to Group 1 or Group 2 in the crossover phase were injected with ranibizumab on an as-needed basis.

Participants with one eye assigned in either Group 1 or Group 2 who had at least one follow-up visit in the post-36-week extension are included in the number of participants at risk.

Participants for whom two eyes were assigned (bilateral participants) are not included.

Post-36-Week Extension Phase: Eyes assigned to Group 3 or Group 4 in the crossover phase were injected with bevacizumab on an as-needed basis.

Participants with one eye assigned in either Group 3 or Group 4 who had at least one follow-up visit in the post-36-week extension are included in the number of participants at risk.

Participants for whom two eyes were assigned (bilateral participants) are not included.

Post-36-Week Extension Phase: Eyes assigned to Group 1 or Group 2 in the crossover phase were injected with ranibizumab on an as-needed basis. Eyes assigned to Group 3 or Group 4 in the crossover phase were injected with bevacizumab on an as-needed basis.

Participants with two eyes assigned who had at least one follow-up visit in the post-36-week extension are included in the number of participants at risk.

Participants for whom one eye was assigned (unilateral participants) are not included.

All-Cause Mortality
Group 1 - Ranibizumab-Ranibizumab-Bevacizumab Injection Series Group 2 - Ranibizumab-Bevacizumab-Bevacizumab Injection Series Group 3 - Bevacizumab-Bevacizumab-Ranibizumab Injection Series Group 4 - Bevacizumab-Ranibizumab-Ranibizumab Injection Series Ranibizumab As Needed (Post-36-Week Extension) Bevacizumab As Needed (Post-36-Week Extension) Ranibizumab and Bevacizumab As Needed (Post-36-Week Extension)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Group 1 - Ranibizumab-Ranibizumab-Bevacizumab Injection Series Group 2 - Ranibizumab-Bevacizumab-Bevacizumab Injection Series Group 3 - Bevacizumab-Bevacizumab-Ranibizumab Injection Series Group 4 - Bevacizumab-Ranibizumab-Ranibizumab Injection Series Ranibizumab As Needed (Post-36-Week Extension) Bevacizumab As Needed (Post-36-Week Extension) Ranibizumab and Bevacizumab As Needed (Post-36-Week Extension)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/16 (18.75%)      1/13 (7.69%)      1/14 (7.14%)      1/13 (7.69%)      1/25 (4.00%)      0/24 (0.00%)      0/4 (0.00%)    
Cardiac disorders               
Arrhythmia  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hepatobiliary disorders               
Cholecystitis  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations               
Osteomyelitis  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Cellulitis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Localised infection  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Pneumonia  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Investigations               
Blood glucose increased  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorders               
Cerebral haemorrhage  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Syncope  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Group 1 - Ranibizumab-Ranibizumab-Bevacizumab Injection Series Group 2 - Ranibizumab-Bevacizumab-Bevacizumab Injection Series Group 3 - Bevacizumab-Bevacizumab-Ranibizumab Injection Series Group 4 - Bevacizumab-Ranibizumab-Ranibizumab Injection Series Ranibizumab As Needed (Post-36-Week Extension) Bevacizumab As Needed (Post-36-Week Extension) Ranibizumab and Bevacizumab As Needed (Post-36-Week Extension)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/16 (81.25%)      12/13 (92.31%)      9/14 (64.29%)      9/13 (69.23%)      13/25 (52.00%)      12/24 (50.00%)      4/4 (100.00%)    
Cardiac disorders               
Cardiac failure congestive  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Ear and labyrinth disorders               
Vertigo  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Eye disorders               
Blepharitis  1  0/16 (0.00%)  0 1/13 (7.69%)  2 1/14 (7.14%)  2 1/13 (7.69%)  2 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Blepharospasm  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Cataract  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Conjunctival haemorrhage  1  0/16 (0.00%)  0 2/13 (15.38%)  2 2/14 (14.29%)  2 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Conjunctivitis  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Corneal erosion  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Dry eye  1  1/16 (6.25%)  2 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Eye pain  1  2/16 (12.50%)  2 2/13 (15.38%)  2 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Eye pruritis  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Eyelid oedema  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Lenticular opacities  1  0/16 (0.00%)  0 1/13 (7.69%)  2 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Posterior capsule opacification  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Retinal haemorrhage  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 2/4 (50.00%)  2
Vision blurred  1  0/16 (0.00%)  0 2/13 (15.38%)  3 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Vitreous detachment  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Vitreous haematoma  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Vitreous haemorrhage  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 3/24 (12.50%)  4 0/4 (0.00%)  0
Gastrointestinal disorders               
Abdominal discomfort  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 1/4 (25.00%)  1
Colitis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Constipation  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 2/24 (8.33%)  2 0/4 (0.00%)  0
Diarrhoea  1  1/16 (6.25%)  1 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Tongue ulceration  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Vomiting  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
General disorders               
Adverse drug reaction  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Chest pain  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Influenza like illness  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 2/24 (8.33%)  2 0/4 (0.00%)  0
Malaise  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Oedema peripheral  1  1/16 (6.25%)  1 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Peripheral swelling  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  2 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Pyrexia  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hepatobiliary disorders               
Early satiety  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hepatic cirrhosis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Immune system disorders               
Drug hypersensitivity  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hypersensitivity  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Infections and infestations               
Cellulitis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Ear infection  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Gastroenteritis viral  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 1/24 (4.17%)  1 1/4 (25.00%)  1
Influenza  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Localised infection  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Lower respiratory tract infection  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Nasopharyngitis  1  0/16 (0.00%)  0 1/13 (7.69%)  1 1/14 (7.14%)  1 3/13 (23.08%)  3 1/25 (4.00%)  1 0/24 (0.00%)  0 1/4 (25.00%)  1
Otitis media  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Pneumonia  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Respiratory tract infection  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Respiratory tract infection viral  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Sinusitis  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Tonsillitis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Upper respiratory tract infection  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Urinary tract infection  1  1/16 (6.25%)  1 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 1/25 (4.00%)  1 2/24 (8.33%)  2 0/4 (0.00%)  0
Viral infection  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Injury, poisoning and procedural complications               
Chest injury  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Corneal abrasion  1  1/16 (6.25%)  2 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 1/24 (4.17%)  1 0/4 (0.00%)  0
Fall  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Procedural nausea  1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Stress fracture  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Wound  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Wrist fracture  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 2/13 (15.38%)  2 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Investigations               
Albumin urine present  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Blood iron decreased  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Intraocular pressure increased  1  2/16 (12.50%)  2 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Lymphocte count decreased  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Metabolism and nutrition disorders               
Dehydration  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Gout  1  1/16 (6.25%)  1 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hyperkalaemia  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Arthralgia  1  2/16 (12.50%)  2 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Back pain  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Musculoskeletal pain  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 2/13 (15.38%)  2 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Myalgia  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Neck pain  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Pain in extremity  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 2/24 (8.33%)  2 1/4 (25.00%)  1
Rheumatoid arthritis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 0/4 (0.00%)  0
Nervous system disorders               
Diabetic neuropathy  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Dizziness  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hyposmia  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
IIIrd nerve paralysis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
IVth nerve paralysis  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Sciatica  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Subarachnoid haemorrhage  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
VIIth nerve paralysis  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Psychiatric disorders               
Anxiety  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Depressed mood  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Depression  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Reproductive system and breast disorders               
Breast mass  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Asthma  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 1/4 (25.00%)  1
Cough  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 1/25 (4.00%)  1 0/24 (0.00%)  0 1/4 (25.00%)  1
Epistaxis  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Sinus congestion  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Skin and subcutaneous tissue disorders               
Blister  1  1/16 (6.25%)  1 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Dermatitis contact  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Rash  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Skin lesion  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  1 0/4 (0.00%)  0
Surgical and medical procedures               
Cyst removal  1  0/16 (0.00%)  0 1/13 (7.69%)  1 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Vascular disorders               
Hypertension  1  0/16 (0.00%)  0 0/13 (0.00%)  0 1/14 (7.14%)  1 1/13 (7.69%)  1 0/25 (0.00%)  0 0/24 (0.00%)  0 0/4 (0.00%)  0
Hypotension  1  0/16 (0.00%)  0 0/13 (0.00%)  0 0/14 (0.00%)  0 0/13 (0.00%)  0 0/25 (0.00%)  0 1/24 (4.17%)  2 0/4 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (Unspecified)
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.
No outcome data should be presented until after a manuscript is accepted for publication.
Results Point of Contact
Name/Title: Henry E Wiley, MD, Principal Investigator
Organization: National Eye Institute (NEI) at National Institutes of Health (NIH)
Phone: (301) 451-4260
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )
ClinicalTrials.gov Identifier: NCT01610557     History of Changes
Other Study ID Numbers: 120134
12-EI-0134
First Submitted: May 31, 2012
First Posted: June 4, 2012
Results First Submitted: February 11, 2016
Results First Posted: April 27, 2016
Last Update Posted: August 19, 2016