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Intravitreal Ranibizumab for Vitreous Hemorrhage Due to Proliferative Diabetic Retinopathy (N) (N)

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ClinicalTrials.gov Identifier: NCT00996437
Recruitment Status : Completed
First Posted : October 16, 2009
Results First Posted : May 16, 2013
Last Update Posted : August 26, 2016
Sponsor:
Collaborator:
National Eye Institute (NEI)
Information provided by (Responsible Party):
Jaeb Center for Health Research

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Vitreous Hemorrhage
Proliferative Diabetic Retinopathy
Interventions Drug: Ranibizumab
Drug: Saline
Enrollment 261
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Period Title: Overall Study
Started 125 136
Completed 120 129
Not Completed 5 7
Reason Not Completed
Death             1             0
Dropped             2             2
Missed             2             5
Arm/Group Title Ranibizumab Saline Injection Total
Hide Arm/Group Description Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks Total of all reporting groups
Overall Number of Baseline Participants 125 136 261
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Median (Inter-Quartile Range)
Unit of measure:  Years
Number Analyzed 125 participants 136 participants 261 participants
61
(50 to 67)
58
(49 to 64)
59
(50 to 66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Female
65
  52.0%
70
  51.5%
135
  51.7%
Male
60
  48.0%
66
  48.5%
126
  48.3%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
White 67 70 137
African-American 20 22 42
Hispanic or Latino 32 34 66
Asian 1 4 5
Native Hawaiian/Other Pacific Islander 2 1 3
American Indian/Alaskan Native 0 2 2
More than one race 2 1 3
Unknown/not reported 1 2 3
Diabetes Type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Type1 21 31 52
Type 2 101 99 200
Uncertain 3 6 9
Duration of Diabetes (years)  
Median (Inter-Quartile Range)
Unit of measure:  Number
Number Analyzed 125 participants 136 participants 261 participants
19
(12 to 28)
21
(16 to 27)
20
(13 to 27)
Hemoglobin A1c  
Median (Inter-Quartile Range)
Unit of measure:  Percentage
Number Analyzed 125 participants 136 participants 261 participants
7.7
(6.7 to 8.7)
8.0
(6.9 to 9.3)
7.9
(6.8 to 9.0)
Pre-Existing Cardiovascular Conditions  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Yes 44 60 104
No 81 76 157
Pre-Existing Hypertension  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Yes 105 117 222
No 20 19 39
Prior panretinal photocoagulation  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Yes 62 78 140
No 63 58 121
Prior Treatment for Diabetic Macular Edema  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Yes 53 57 110
No 72 79 151
Prior treatment with anti-vascular endothelial growth factor drug for diabetic macular edema  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Yes 10 18 28
No 115 118 233
Lens Status (on clinical exam)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Phakic 97 98 195
Posterior Chamber Intraocular Lens 28 38 66
Optical coherence tomography signal strength   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
=0 74 96 170
> 0 50 38 88
Missing/not available 1 2 3
[1]
Measure Description: The Ns represent the total number of available baseline optical coherence tomography signal strengths data. Optical Coherence Tomography Signal strength is measured on a scale of 0-10 with 10 being the maximum signal strength, a greater signal strength indicates a better image.
Ultrasound completed to assess eligibility  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Yes 62 62 124
No 63 74 137
Duration of vitreous hemorrhage since first documented on clinical exam  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
< 1month 66 75 141
1-3 months 41 39 80
4-6 months 7 11 18
> 6 months 11 11 22
Median Electronic-Early Treatment Diabetic Retinopathy Visual Acuity (letter score)   [1] 
Median (Inter-Quartile Range)
Unit of measure:  Units on a scale
Number Analyzed 125 participants 136 participants 261 participants
34
(0 to 61)
28
(0 to 59)
31
(0 to 61)
[1]
Measure Description: Visual Acuity was measured with the Electronic Early Treatment Study (E-ETDRS) visual acuity test. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best
Electronic Early Treatment Diabetic Retinopathy Visual Acuity Score   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
> 69 letter score - (20/40 or better) 20 21 41
68 to 49 letter score - (20/50 to 20/100) 32 19 51
48 to 24 letter score - (20/125 to 20/320) 18 37 55
23 to 1 letter score - (20/400 to 20/800-3) 19 18 37
Counting fingers only 12 15 27
Hand motion only 19 20 39
Light perception only 5 6 11
No light perception 0 0 0
[1]
Measure Description: Visual Acuity Electronic Early Treatment Study (E-ETDRS) visual acuity test (Letter Score [snellen equivalent]). Letter score and its snellen equivalent (categorical) are reported. Unit of measure is based on the E-ETDRS letter score scale, 0-97, where 0 = worst and 97 = best.
Intraocular Pressure  
Median (Inter-Quartile Range)
Unit of measure:  Mm Hg
Number Analyzed 125 participants 136 participants 261 participants
15
(12 to 17)
14
(12 to 17)
15
(12 to 17)
Anti-platelet aggregation and anti-coagulant drugs   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 125 participants 136 participants 261 participants
Aspirin 50 57 107
Other anti-platelet aggregation drugs 19 21 40
Anti-coagulants 7 6 13
NSAIDs 15 15 30
Not Available 34 37 71
[1]
Measure Description: The Ns represent concomitant medications reported throughout the study duration. Please notice that these might not be equal to the number of participants enrolled.
1.Primary Outcome
Title Treatment or "Failure" Defined as Vitrectomy
Hide Description The cumulative probabilities of vitrectomy by 16 weks (112 days) in each group were computed using the life-table method. The treatment group comparison was made using the log-rank test. Data were censored at the time point of the participant's last completed visit.
Time Frame within 112 days of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The primary analysis followed the intent-to-treat principle and included all randomized eyes.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: percentage of participants
12 17
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab, Saline Injection
Comments The cumulative probabilities of vitrectomy by 16 weeks in each group were computed using the life-table method. Treatment group comparisons were performed using the log-rank test. The treatment difference in cumulative probabilities and 95% confidence interval were reported.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.37
Comments [Not Specified]
Method Log Rank
Comments After adjusting for potential confounding factors, time to vitrectomy remained similar between treatment groups.
Method of Estimation Estimation Parameter Treatment Difference in Cumulative Prob
Estimated Value 4
Confidence Interval (2-Sided) 95%
-4 to 13
Estimation Comments [Not Specified]
2.Primary Outcome
Title Safety (Injected-related, Ocular Drug-related and Systemic Drug-related)
Hide Description [Not Specified]
Time Frame Baseline to 16 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Adverse events for each participants was collected throughout study duration.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: participants
Endophthalmitis 0 1
Traction and/or rhegmatogeneous retinal detachment 10 11
Angle or iris neovascularization 1 4
Neovascular glaucoma 1 1
Cataract Surgery 0 2
Recurrent vitreous hemorrhage on clinical exam 8 23
Elevated Intraocular Pressure (IOP)/Glaucoma 16 19
Increase of IOP >= 10 mm Hg from baseline 8 11
IOP >= 30 mm Hg 4 4
Currently on IOP-lowering medication, not baseline 13 14
Glaucoma surgery at anytime 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab, Saline Injection
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.01
Comments P-value corresponds with recurrent vitreous hemorrhage evaluated on clinical exam between the two treatment arms.
Method Fisher Exact
Comments [Not Specified]
3.Secondary Outcome
Title Ability to Complete Panretinal Photocoagulation (PRP) in the Absence of Vitrectomy
Hide Description The proportion of eyes with "complete" panretinal photocoagulation by 16 weeks in abscence of vitrectomy was computed using the life-table method and treatment groups were compared using the log-rank test.
Time Frame within 112 days of randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The secondary analysis followed the intent-to-treat principle and included all randomized eyes.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: percentage of eyes
44 31
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab, Saline Injection
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.05
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.54
Confidence Interval (2-Sided) 95%
1.03 to 2.30
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Extent of Vitreous Hemorrhage Measured by Optical Coherence Tomography Signal Strength
Hide Description Optical coherence tomography signal strength was evaluated as a potential indicator of vitreous hemorrhage density in an exploratory analysis. This analysis included only eyes with Optical Coherence Tomography (OCT) signal strength equals to 0 at baseline.
Time Frame 4, 8 and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis followed the intent-to-treat principle
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: percentage of eyes
4 week results 40 28
8 week results 46 38
12 week results 51 52
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab, Saline Injection
Comments Signal strength was analyzed as a composite outcome defined as OCT signal strength > = and no vitrectomy vs. OCT signal strength = 0.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.87
Comments P-value corresponds to the 12 week visit treatment comparison.
Method GLM with GEE method
Comments Number of subjects with baseline OCT ss=0 and OCT ss>0 and no vitrectomy at follow up. A generalized GLM with GEE was used for treatment comparisons.
5.Secondary Outcome
Title Visual Acuity Adjusted for the Baseline Acuity Regardless of Vitrectomy Status
Hide Description Visual acuity was analyzed using a longitudinal mixed regression model adjusting for baseline visual acuity.Unit of measure is based on the E-ETDRS visual acuity letter score scale, 0-97, where 0 = worst and 97 = best.
Time Frame 4, 8 and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Number of participants with a complete 4 week visit, 8 and 12 week respectively and an available visual acuity measurement.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Mean (Standard Deviation)
Unit of Measure: letter scores
4 week results 45  (30) 42  (31)
8 week results 51  (30) 47  (31)
12 week results 57  (27) 49  (29)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab, Saline Injection
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .04
Comments P-value corresponds to the 12 week visit treatment comparison.
Method Mixed Models Analysis
Comments Treatment comparisons were performed using a longitudinal mixed model adjusting for baseline visual acuity.
6.Secondary Outcome
Title Visual Acuity Better Than 20/40 and no Vitrectomy Prior to the Visit
Hide Description [Not Specified]
Time Frame 4, 8 and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This analysis followed the intent-to-treat principle. It includes all randomized eyes with a completed 4, 8 and 12 week visit respectively and an available visual acuity measure.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: percentage of participants
4 week results 29 29
8 week results 36 33
12 week results 45 33
7.Secondary Outcome
Title Severe Visual Acuity Loss (Defined as <20/200)
Hide Description [Not Specified]
Time Frame 4,8 and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participant with a completed 4,8 and 12 week visit and an available visual acuity measurement were included in this analysis.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: percentage of participants
4 week results 38 38
8 week results 30 35
12 week results 20 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab, Saline Injection
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .023
Comments P-value corresponds with the 12 week visit treatment comparison
Method Fisher Exact
Comments At the each time point, treatment comparison analysis was performed using a Fisher Exact test.
8.Secondary Outcome
Title Very Severe Visual Acuity Loss (Defined as <20/800)
Hide Description [Not Specified]
Time Frame 4,8 and 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with a completed 4, 8 and 12 week visit respectively and an available visual acuity measurement were included in the analysis.
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description:
Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks
Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
Overall Number of Participants Analyzed 125 136
Measure Type: Number
Unit of Measure: percentage of participants
4 week results 20 25
8 week results 16 19
12 week results 11 16
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ranibizumab
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.27
Comments [Not Specified]
Method Fisher Exact
Comments At each time point, treatment comparison analysis was performed using a Fisher Exact Test.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ranibizumab Saline Injection
Hide Arm/Group Description Ranibizumab : Intravitreal injection of 0.5 mg ranibizumab (Lucentis™) at baseline, 4 and 8 weeks Saline : Saline injection of 0.5mg at baseline, 4 and 8 weeks
All-Cause Mortality
Ranibizumab Saline Injection
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Ranibizumab Saline Injection
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/125 (10.40%)      23/136 (16.91%)    
Cardiac disorders     
Angina pectoris  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Congestive cardiac failure  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Cardiomegaly  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Myocardial Infarction  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Endocrine disorders     
Diabetic gastroparesis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Hypoglycaemia  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Eye disorders     
Endophthalmitis * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Retinal detachment * 1  3/125 (2.40%)  3 4/136 (2.94%)  5
Glaucoma  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Retinal Tear  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Visual acuity reduced * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Gastrointestinal disorders     
Abdominal Pain  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Appendicitis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Vomiting  1  0/125 (0.00%)  0 1/136 (0.74%)  1
General disorders     
Chest pain * 1  1/125 (0.80%)  1 0/136 (0.00%)  0
Death  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Infections and infestations     
Bronchopneumonia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Gastroenteritis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Herpes Zoster  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Osteomyelitis  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Pneumonia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Metabolism and nutrition disorders     
Hyperkalaemia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Musculoskeletal and connective tissue disorders     
Back Pain * 1  1/125 (0.80%)  1 0/136 (0.00%)  0
Upper limb fracture  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Psychiatric disorders     
Depression  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Renal and urinary disorders     
Haematuria  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Renal Faliure  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Renal Failure Acute  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Hypoxia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Respiratory distress  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Skin and subcutaneous tissue disorders     
Cellulitis  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Skin Ulcer  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Vascular disorders     
Diabetic foot  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Hypertension  1  0/125 (0.00%)  0 3/136 (2.21%)  3
Intermittent claudication  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Peripheral vascular disorder  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Transient ishaemic attack  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Ranibizumab Saline Injection
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   84/125 (67.20%)      94/136 (69.12%)    
Blood and lymphatic system disorders     
Anaemia  1  2/125 (1.60%)  2 3/136 (2.21%)  3
Anaemia of chronic disease  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Leukocytosis  1  2/125 (1.60%)  2 0/136 (0.00%)  0
Cardiac disorders     
Atrial fibrilliation  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Cardiomegaly  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Ear and labyrinth disorders     
Otitis media acute  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Endocrine disorders     
Diabetes mellitus inadequate control * 1  1/125 (0.80%)  1 1/136 (0.74%)  1
Hyperglycaemia  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Hypoglycaemia  1  0/125 (0.00%)  0 3/136 (2.21%)  3
Hypthyroidism  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Eye disorders     
Anterior chamber cell  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Anterior chamber flare  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Aphkia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Blepharitis  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Borderline glaucoma  1  1/125 (0.80%)  1 2/136 (1.47%)  2
Cataract  1  5/125 (4.00%)  5 7/136 (5.15%)  7
Cataract cortical  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Cataract nuclear  1  2/125 (1.60%)  3 0/136 (0.00%)  0
Cataract operation complication  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Cataract subcapsular  1  2/125 (1.60%)  2 3/136 (2.21%)  3
Choroidal detachment  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Conjunctival hemorrhage  1  7/125 (5.60%)  11 7/136 (5.15%)  10
Conjunctival hyperaemia  1  0/125 (0.00%)  0 2/136 (1.47%)  3
Conjunctivitis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Corneal abrasion  1  2/125 (1.60%)  3 1/136 (0.74%)  1
Corneal defect  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Diabetic retinal oedema  1  3/125 (2.40%)  3 3/136 (2.21%)  3
Diabetic retinopathy  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Diplopia  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Dry eye  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Eye discharge  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Eye irritation  1  3/125 (2.40%)  4 3/136 (2.21%)  4
Eye pain * 1  14/125 (11.20%)  18 14/136 (10.29%)  15
Eye pruritus  1  1/125 (0.80%)  1 3/136 (2.21%)  6
Eyelid ptosis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Eyelid oedema  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Foreign body sensation in eyes * 1  3/125 (2.40%)  3 0/136 (0.00%)  0
Glaucoma  1  2/125 (1.60%)  2 4/136 (2.94%)  4
Hordeolum  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Hyphaema  1  2/125 (1.60%)  2 0/136 (0.00%)  0
Iris neovascularization  1  0/125 (0.00%)  0 3/136 (2.21%)  3
Irititis  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Keratitis  1  2/125 (1.60%)  2 0/136 (0.00%)  0
Lacrimation increased  1  4/125 (3.20%)  4 2/136 (1.47%)  2
Macular cyst  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Macular fibrosis  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Macular ischaemia  1  0/125 (0.00%)  0 1/136 (0.74%)  2
Mascular oedema  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Maculopathy  1  5/125 (4.00%)  5 2/136 (1.47%)  2
Metamorphosia  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Night blindness * 1  0/125 (0.00%)  0 1/136 (0.74%)  2
Ocular discomfort * 1  2/125 (1.60%)  2 1/136 (0.74%)  1
Ocular hyperaemia  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Ocular hypertension  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Optic atrophy  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Photophobia  1  1/125 (0.80%)  2 1/136 (0.74%)  1
Photopsia  1  4/125 (3.20%)  6 3/136 (2.21%)  5
Posterior capsule opacification  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Punctate keratitis  1  0/125 (0.00%)  0 2/136 (1.47%)  3
Retinal aneurysm  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Retinal detachment  1  6/125 (4.80%)  7 7/136 (5.15%)  7
Retinal disorder  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Retinal haemorrhage  1  1/125 (0.80%)  1 2/136 (1.47%)  2
Retinal neovascularization  1  0/125 (0.00%)  0 4/136 (2.94%)  5
Retinal tear  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Vision blurred * 1  8/125 (6.40%)  10 11/136 (8.09%)  12
Visual acuity reduced  1  6/125 (4.80%)  6 7/136 (5.15%)  7
Visual field defect  1  1/125 (0.80%)  2 0/136 (0.00%)  0
Visual impairment * 1  5/125 (4.00%)  7 2/136 (1.47%)  2
Vitreous detachment  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Vitreous disorder  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Vitreous floaters  1  14/125 (11.20%)  15 11/136 (8.09%)  14
Vitreous hemorrhage  1  16/125 (12.80%)  17 20/136 (14.71%)  25
Gastrointestinal disorders     
Abdominal discomfort * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Abdominal pain * 1  0/125 (0.00%)  0 2/136 (1.47%)  2
Diarrhoea * 1  5/125 (4.00%)  5 1/136 (0.74%)  1
Nausea * 1  8/125 (6.40%)  10 2/136 (1.47%)  2
Vomiting  1  2/125 (1.60%)  2 1/136 (0.74%)  1
General disorders     
Chest pain * 1  1/125 (0.80%)  1 1/136 (0.74%)  1
Chills * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Constipation * 1  2/125 (1.60%)  2 1/136 (0.74%)  1
Facial pain * 1  1/125 (0.80%)  1 0/136 (0.00%)  0
Fatigue * 1  1/125 (0.80%)  1 0/136 (0.00%)  0
Oedema peripheral  1  0/125 (0.00%)  0 4/136 (2.94%)  5
Pyrexia  1  1/125 (0.80%)  1 1/136 (0.74%)  2
Hepatobiliary disorders     
Ascites  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Immune system disorders     
Hypersensitivity  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Seasonal allergy  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Urticaria  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Infections and infestations     
Bronchitis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Cystitis  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Ear infection  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Gastroenteritis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Herpes Zoster  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Influenza  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Localised infection  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Osteomyelitis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Skin infection  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Upper respiratory tract infection  1  4/125 (3.20%)  4 3/136 (2.21%)  3
Urinary tract infection  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Injury, poisoning and procedural complications     
Fall * 1  2/125 (1.60%)  2 1/136 (0.74%)  1
Foot fracture  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Laceration  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Upper limb fracture  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Wound  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Investigations     
Blood potasium increased  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Intra ocular pressure increased  1  1/125 (0.80%)  1 1/136 (0.74%)  1
Mammogram abnormal  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Metabolism and nutrition disorders     
Hypercholesterolaemia  2  0/125 (0.00%)  0 1/136 (0.74%)  1
Hyperlipidaemia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Hypokalaemia  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Malnutrition  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/125 (0.80%)  1 2/136 (1.47%)  2
Multiple fractures  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Muscle spasm  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Neck pain * 1  0/125 (0.00%)  0 3/136 (2.21%)  3
Osteoarthritis  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Pain in extremity * 1  0/125 (0.00%)  0 3/136 (2.21%)  3
Tendonitis  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Trigger finger  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colonic polyp  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Nervous system disorders     
Carpal tunnel syndrome  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Dizziness * 1  1/125 (0.80%)  1 1/136 (0.74%)  1
Headache * 1  0/125 (0.00%)  0 9/136 (6.62%)  9
Migraine  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Migraine * 1  1/125 (0.80%)  1 0/136 (0.00%)  0
Muscular weakness * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Parkison's disease  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Syncope  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Vertigo * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Renal and urinary disorders     
Nephrolithiasis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Renal failure  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Renal failure acute  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Renal failure chronic  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Renal imparment  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Cough * 1  4/125 (3.20%)  4 4/136 (2.94%)  4
Dyspnoea  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Epistaxis  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Lung neoplasm  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Nasal congestion * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Nasopharyngitis  1  5/125 (4.00%)  5 4/136 (2.94%)  4
Oropharyngeal pain * 1  0/125 (0.00%)  0 3/136 (2.21%)  3
Pulmonary oedema  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Sinusitis  1  2/125 (1.60%)  2 0/136 (0.00%)  0
Sleep apnoea syndrome * 1  0/125 (0.00%)  0 1/136 (0.74%)  1
Skin and subcutaneous tissue disorders     
Cellulitis  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Dermal cyst  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Eczema  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Skin ulcer  1  0/125 (0.00%)  0 2/136 (1.47%)  2
Surgical and medical procedures     
Coronary arterial stent insertion  1  0/125 (0.00%)  0 1/136 (0.74%)  1
Vascular disorders     
Arteriovenous fistula  1  2/125 (1.60%)  2 1/136 (0.74%)  1
Diabetic foot  1  1/125 (0.80%)  1 0/136 (0.00%)  0
Hypertension  1  3/125 (2.40%)  3 4/136 (2.94%)  4
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
2
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Adam R. Glassman
Organization: Diabetic Retinopathy Clinical Research Network
Phone: 813-975-8761
Responsible Party: Jaeb Center for Health Research
ClinicalTrials.gov Identifier: NCT00996437     History of Changes
Other Study ID Numbers: NEI-151
U10EY018817-03 ( U.S. NIH Grant/Contract )
U10EY014231-09 ( U.S. NIH Grant/Contract )
First Submitted: October 14, 2009
First Posted: October 16, 2009
Results First Submitted: February 19, 2013
Results First Posted: May 16, 2013
Last Update Posted: August 26, 2016