Trial Outcomes & Findings for Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Central Retinal Vein Occlusion (CRVO) (NCT NCT01976312)

NCT ID: NCT01976312

Last Updated: 2017-05-30

Results Overview

Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters. Mean Visual Acuity was averaged over all monthly assessments from month 1 to month 3 and compared to Baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

252 participants

Primary outcome timeframe

Baseline, 3 Months

Results posted on

2017-05-30

Participant Flow

A total of 253 patients were randomized to this study, 191 patients to the ranibizumab group and 62 patients to the sham group. One patient randomized to the ranibizumab group was excluded from all analyses as informed consent was obtained after first study procedures were performed. Therefore, this patient not included in randomized set.

This study consisted of the 3 periods (Screening period: Day -14 to Day -1; treatment period: Day 1 to Month 11; post-treatment period: Month 11 to Month 12). At Baseline (Visit 2, Day 1), eligible patients were randomized in a 3:1 ratio to one of the treatment arms

Participant milestones

Participant milestones
Measure	Ranibizumab 0.5 mg PRN intravitreal injection	Sham Injection As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Overall Study STARTED	190	62
Overall Study Completed 3 Months	186	60
Overall Study Discontinued Study Prior to 3 Months	4	2
Overall Study COMPLETED	173	53
Overall Study NOT COMPLETED	17	9

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab 0.5 mg PRN intravitreal injection	Sham Injection As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Overall Study Pregnancy	0	1
Overall Study Lost to Follow-up	2	0
Overall Study Withdrawal by Subject	7	2
Overall Study Adverse Event	6	6
Overall Study Protocol Violation	2	0

Baseline Characteristics

Ranibizumab Intravitreal Injections Versus Sham Control in Patients With Central Retinal Vein Occlusion (CRVO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab 0.5 mg n=190 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections	Total n=252 Participants Total of all reporting groups
Age, Continuous	54.1 Years STANDARD_DEVIATION 12.64 • n=5 Participants	54.1 Years STANDARD_DEVIATION 13.29 • n=7 Participants	54.1 Years STANDARD_DEVIATION 12.77 • n=5 Participants
Sex: Female, Male Female	88 Participants n=5 Participants	29 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	102 Participants n=5 Participants	33 Participants n=7 Participants	135 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 3 Months

Population: The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. (MV-LOCF)=Mean value interpolation and last observation carried forward

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Average Change in Visual Acuity (Letters) From Baseline to Month 1 Through Month 3	11.3 Letters Standard Deviation 10.77	-2.7 Letters Standard Deviation 13.92

SECONDARY outcome

Timeframe: Baseline, 12 months

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Average Change of Best Corrected Visual Acuity (BCVA) From Baseline to Month 1 Through Month 12	12.4 Letters Standard Deviation 11.43	3.2 Letters Standard Deviation 14.62

SECONDARY outcome

Timeframe: Month 1 to 12 months

Visual acuity (VA) was assessed on both eyes during every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes the change in visual acuity at each visit compared to baseline

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 1	9.6 Letters Standard Deviation 10.2	-0.9 Letters Standard Deviation 12.17
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 2	11.6 Letters Standard Deviation 12.39	-3.4 Letters Standard Deviation 16.04
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 3	12.6 Letters Standard Deviation 12.01	-3.8 Letters Standard Deviation 17.02
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 4	10.7 Letters Standard Deviation 12.56	2.8 Letters Standard Deviation 15.26
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 5	11.7 Letters Standard Deviation 12.62	3.9 Letters Standard Deviation 15.26
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 6	12.3 Letters Standard Deviation 13.10	3.8 Letters Standard Deviation 17.20
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 7	12.9 Letters Standard Deviation 13.36	5.0 Letters Standard Deviation 16.71
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 8	12.4 Letters Standard Deviation 14.01	6.0 Letters Standard Deviation 16.01
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 9	13.1 Letters Standard Deviation 15.10	5.6 Letters Standard Deviation 16.95
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 10	13.5 Letters Standard Deviation 14.13	5.9 Letters Standard Deviation 16.77
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 11	14.2 Letters Standard Deviation 13.15	6.8 Letters Standard Deviation 16.30
Best Corrected Visual Acuity (BCVA) Change From Baseline Over Time Month 12	14.5 Letters Standard Deviation 14.25	6.5 Letters Standard Deviation 17.10

SECONDARY outcome

Timeframe: Month 1 to month 12

OCT (optical coherence tomography) was used to assess CSFT (Central Sub-Field Thickness) representing the average retinal thickness of the circular area within 1 mm diameter around the foveal center.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 1	-393.7 microns Standard Deviation 275.13	-13.3 microns Standard Deviation 207.55
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 2	-412.6 microns Standard Deviation 297.50	-7.9 microns Standard Deviation 196.65
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 3	-433.3 microns Standard Deviation 290.84	-84.4 microns Standard Deviation 274.98
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 4	-367.8 microns Standard Deviation 305.26	-364.8 microns Standard Deviation 250.48
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 5	-407.0 microns Standard Deviation 309.58	-369.6 microns Standard Deviation 273.92
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 6	-426.6 microns Standard Deviation 294.63	-372.3 microns Standard Deviation 301.24
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 7	-421.5 microns Standard Deviation 316.14	-392.7 microns Standard Deviation 288.74
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 8	-398.9 microns Standard Deviation 299.67	-405.2 microns Standard Deviation 289.49
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 9	-422.1 microns Standard Deviation 311.57	-393.5 microns Standard Deviation 323.50
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 10	-431.7 microns Standard Deviation 300.95	-395.2 microns Standard Deviation 309.67
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 11	-438.1 microns Standard Deviation 295.53	-417.4 microns Standard Deviation 288.08
Change From Baseline in Central-Sub-Field- Thickness (CSFT) Over Time Month 12	-441.7 microns Standard Deviation 306.53	-416.4 microns Standard Deviation 294.08

SECONDARY outcome

Timeframe: Month 1 to month 12

Best Corrected Visual Acuity (BCVA) was assessed in a sitting position using ETDRS-like visual acuity testing charts at an initial testing distance of 4 meters.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=5 letters	141 Participants	17 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=10 letters	94 Participants	6 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=15 letters	56 Participants	2 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 1 Gain of >=30 letters	3 Participants	0 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=5 letters	150 Participants	18 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=10 letters	119 Participants	11 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=15 letters	74 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 2 Gain of >=30 letters	9 Participants	0 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=5 letters	153 Participants	19 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=10 letters	117 Participants	11 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=15 letters	76 Participants	4 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 3 Gain of >=30 letters	12 Participants	0 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=5 letters	138 Participants	31 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=10 letters	107 Participants	21 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=15 letters	68 Participants	11 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 4 Gain of >=30 letters	14 Participants	2 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=5 letters	143 Participants	34 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=10 letters	116 Participants	23 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=15 letters	80 Participants	13 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 5 Gain of >=30 letters	13 Participants	1 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=5 letters	147 Participants	39 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=10 letters	121 Participants	28 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=15 letters	87 Participants	12 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 6 Gain of >=30 letters	14 Participants	13 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=5 letters	152 Participants	37 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=10 letters	121 Participants	29 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=15 letters	91 Participants	14 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 7 Gain of >=30 letters	14 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=5 letters	143 Participants	39 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=10 letters	127 Participants	28 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=15 letters	95 Participants	19 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 8 Gain of >=30 letters	16 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=5 letters	147 Participants	40 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=10 letters	126 Participants	26 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=15 letters	94 Participants	17 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 9 Gain of >=30 letters	17 Participants	3 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=5 letters	152 Participants	39 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=10 letters	128 Participants	29 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=15 letters	95 Participants	16 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 10 Gain of >=30 letters	18 Participants	4 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=5 letters	153 Participants	40 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=10 letters	134 Participants	29 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=15 letters	101 Participants	19 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 11 Gain of >=30 letters	18 Participants	4 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=5 letters	151 Participants	39 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=10 letters	131 Participants	30 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=15 letters	99 Participants	21 Participants
Number of Participants With a Best Corrected Visual Acuity (BCVA) Improvement of ≥5, ≥10, ≥15, and ≥30 Letters Over Time Month 12 Gain of >=30 letters	24 Participants	3 Participants

SECONDARY outcome

Timeframe: Month 1 to 12 months

Visual acuity (VA) was assessed at every study visit using best correction determined from protocol refraction. VA measurements (number of letters correctly identified) were performed with the patient in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a testing distance of 4 meters. This outcome measure describes for each post-baseline month whether or not a patient lost less than 15 letters of VA as compared with baseline.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=188 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 1, Loss of < 15 letters	185 Participants	57 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 2, Loss of < 15 letters	182 Participants	53 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 3, Loss of < 15 letters	182 Participants	51 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 4, Loss of < 15 letters	179 Participants	55 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 5, Loss of < 15 letters	182 Participants	56 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 6, Loss of < 15 letters	180 Participants	53 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 7, Loss of < 15 letters	181 Participants	55 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 8, Loss of < 15 letters	177 Participants	55 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 9, Loss of < 15 letters	177 Participants	56 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 10, Loss of < 15 letters	180 Participants	56 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 11, Loss of < 15 letters	183 Participants	56 Participants
Number of Participants With Best Corrected Visual Acuity (BCVA)Loss of <15 Letters in the Study Eye Over Time Month 12, Loss of < 15 letters	182 Participants	55 Participants

SECONDARY outcome

Timeframe: Month 3,6 and 12

Population: The Full Analysis Set (FAS) consisted of all patients to whom study treatment had been assigned. Following the intent-to-treat principle, patients were analyzed according to the treatment group they had been assigned to at randomization. n= is the number of patients with a value for both baseline and the specific post-baseline visit.

The VFQ-25 consists of 25 vision related questions across 11 vision related subscales, including general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision and peripheral vision, and a general health rating. Items are converted to a 0-100 scale on each subscale and for the composite score where higher scores represents better functioning.

Outcome measures

Outcome measures
Measure	Ranibizumab 0.5 mg n=190 Participants PRN intravitreal injection	Sham Injection n=62 Participants As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections
The Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 3, 6 and 12 Compared to Baseline Month 3	4.4 Scores on a scale Standard Deviation 12.54	0.1 Scores on a scale Standard Deviation 13.78
The Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 3, 6 and 12 Compared to Baseline Month 6	6.7 Scores on a scale Standard Deviation 15.02	2.9 Scores on a scale Standard Deviation 13.33
The Change in Patient Reported Outcomes in NEI-VFQ-25 Score (Composite Score and Subscales) at Month 3, 6 and 12 Compared to Baseline Month 12	8.2 Scores on a scale Standard Deviation 13.70	3.2 Scores on a scale Standard Deviation 15.34

Adverse Events

Ranibizumab 0.5 mg

Serious events: 11 serious events

Other events: 96 other events

Deaths: 0 deaths

Sham With Ranibizumab 0.5 mg

Serious events: 5 serious events

Other events: 32 other events

Deaths: 0 deaths

Sham Without Ranibizumab 0.5 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis

Phone: 862-778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety
Publication restrictions are in place

Restriction type: OTHER

Measure	Ranibizumab 0.5 mg n=190 participants at risk PRN intravitreal injection	Sham With Ranibizumab 0.5 mg n=56 participants at risk As of Month 3, ranibizumab 0.5 mg PRN intravitreal injections	Sham Without Ranibizumab 0.5 mg n=5 participants at risk Sham without Ranibizumab 0.5mg(hereafter referred to as sham group up to Month 3 and sham without ranibizumab after Month 3
Cardiac disorders Acute myocardial infarction	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Cardiac disorders Left ventricular dysfunction	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Angle closure glaucoma	1.1% 2/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Keratitis	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Eye disorders Macular fibrosis	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	20.0% 1/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Gastrointestinal disorders Gastric ulcer	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Infections and infestations Endophthalmitis	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Infections and infestations Herpes zoster	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Infections and infestations Urinary tract infection	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Inflammatory pseudotumour	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Schwannoma	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Haemorrhage intracranial	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Nervous system disorders Transient ischaemic attack	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Respiratory, thoracic and mediastinal disorders Mediastinal cyst	0.53% 1/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	0.00% 0/190 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	1.8% 1/56 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.	0.00% 0/5 The Safety Set consisted of all patients who received at least one application of study treatment and had at least one post-Baseline safety assessment. Patients were analyzed according to the treatment received. The statement that a patient had no AEs also constituted a safety assessment.