Trial Outcomes & Findings for Extension Study to Compare Long-term Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With RVO (NCT NCT01580020)

NCT ID: NCT01580020

Last Updated: 2016-05-17

Results Overview

The number of participants who experienced Adverse events, serious AE and death

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

175 participants

Primary outcome timeframe

6 months

Results posted on

2016-05-17

Participant Flow

A total of 140 patients with (BRVO) completed the core study CRFB002EDE17, and 127 patients with (CRVO) completed the core study CRFB002EDE18. 92 patients with BRVO and 83 patients with CRVO were enrolled into the extension study. A total of 175 patients (113 in the ranibizumab group and 62 in the dexamethasone group) were enrolled

The Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. LOCF=last observation carried forward

Participant milestones

Participant milestones
Measure	Ranibizumab (BRVO) Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitrally	Dexamethasone (CRVO) A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.
Overall Study STARTED	52	40	61	22
Overall Study COMPLETED	51	33	57	20
Overall Study NOT COMPLETED	1	7	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Ranibizumab (BRVO) Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitrally	Dexamethasone (CRVO) A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.
Overall Study Lack of Efficacy	0	5	0	1
Overall Study Withdrawal by Subject	0	1	1	0
Overall Study Adverse Event	1	1	1	1
Overall Study Administrative Problems	0	0	1	0
Overall Study Lost to Follow-up	0	0	1	0

Baseline Characteristics

Extension Study to Compare Long-term Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With RVO

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ranibizumab n=113 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone n=62 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Total n=175 Participants Total of all reporting groups
Age, Continuous	65.6 Years STANDARD_DEVIATION 9.9 • n=5 Participants	63.3 Years STANDARD_DEVIATION 10.3 • n=7 Participants	64.8 Years STANDARD_DEVIATION 10.1 • n=5 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	26 Participants n=7 Participants	90 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	36 Participants n=7 Participants	85 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.

The number of participants who experienced Adverse events, serious AE and death

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=61 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Adverse event	35 Participants	28 Participants	45 Participants	16 Participants
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Serious adverse event	2 Participants	3 Participants	6 Participants	1 Participants
Number of Participants With Adverse Events as a Measure of Safety and Tolerability Death	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, 6 months and 12 months

Population: FAS consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned.

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (EDTRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. The range of BCVA (EDTRS) is 0 to 100 letters. A positive change from baseline of BCVA indicates improvement

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=60 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group Baseline	56.8 Letters read correctly Standard Deviation 10.0	58.3 Letters read correctly Standard Deviation 10.8	53.8 Letters read correctly Standard Deviation 15.7	53.2 Letters read correctly Standard Deviation 16.1
Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group Month 6	77.9 Letters read correctly Standard Deviation 10.6	69.2 Letters read correctly Standard Deviation 11.9	72.6 Letters read correctly Standard Deviation 13.5	64.1 Letters read correctly Standard Deviation 24.0
Raw Mean Best Corrected Visual Acuity (BCVA) by Treatment Group Month 12	79.0 Letters read correctly Standard Deviation 10.1	70.6 Letters read correctly Standard Deviation 13.9	72.6 Letters read correctly Standard Deviation 15.8	66.6 Letters read correctly Standard Deviation 22.3

SECONDARY outcome

Timeframe: 12 month

Population: Full Analysis Sets (FAS) consisted of all patients from the FAS of the respective core study who had received at least one application of study treatment and had at least one post- baseline assessment for BCVA during the extension study. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20. An increased score indicates improvement in acuity. This outcome assessed the percentage of participants who were gaining/losing ≥15, 10 or 5 more letters of visual acuity at month 12 as compared with baseline

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=60 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline Gain≥15 letters	80.8 Percentage of participants	50.0 Percentage of participants	58.3 Percentage of participants	45.5 Percentage of participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline Gain ≥10 letters	88.5 Percentage of participants	65.0 Percentage of participants	75.0 Percentage of participants	68.2 Percentage of participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline Gain ≥5 letters	100.0 Percentage of participants	80.0 Percentage of participants	86.7 Percentage of participants	77.3 Percentage of participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline Loss of ≥15 letters	0.0 Percentage of participants	7.5 Percentage of participants	0.0 Percentage of participants	4.5 Percentage of participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline Loss of ≥10 letters	0.0 Percentage of participants	10.0 Percentage of participants	0.0 Percentage of participants	4.5 Percentage of participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters at Month 12 Compared to Baseline Loss of ≥5 letters	0.0 Percentage of participants	10.0 Percentage of participants	3.3 Percentage of participants	4.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline , Month 12

High Resolution OCT was performed at every study visit by Spectral Domain OCT (if not available Time Domain OCT was acceptable) and the images were transferred to a digital video disc. These assessments were performed by trained and adequately qualified experts at the sites and prior to any study drug administration. CSFT is the average retinal thickness of the circular area with 1 mm diameter around the foveal center.

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=59 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Change in Central Subfield Thickness (CSRT) From Baseline to Month 12	-288.1 um Standard Deviation 180.6	-211.5 um Standard Deviation 199.3	-374.6 um Standard Deviation 239.8	-360.3 um Standard Deviation 260.2

SECONDARY outcome

Timeframe: Baseline, Month 12

FCPT (foveal center point thickness) was assessed by central reading center to ensure error- corrected measurements of retinal thickness and volumes,

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=51 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=39 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=58 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=21 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Change of Foveal Center Point Thickness (FCPT) From Baseline to Month 12	-341.8 um Standard Deviation 226.2	-252.6 um Standard Deviation 197.9	-439.4 um Standard Deviation 279.8	-432.3 um Standard Deviation 245.8

SECONDARY outcome

Timeframe: Baseline, 12 months

The VFQ-25 composite and subscale scores range from 0 to 100, a higher score indicating better functioning. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated improvement in quality of life due to vision function.

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=60 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Change in Mean Visual Function Questionnaire (VFQ-25) General Health	-1.4 Scores on a scale Standard Deviation 15.2	6.3 Scores on a scale Standard Deviation 18.6	1.7 Scores on a scale Standard Deviation 18.9	5.7 Scores on a scale Standard Deviation 20.3
Change in Mean Visual Function Questionnaire (VFQ-25) Social Functioning	3.4 Scores on a scale Standard Deviation 16.8	2.2 Scores on a scale Standard Deviation 12.0	3.3 Scores on a scale Standard Deviation 16.7	2.8 Scores on a scale Standard Deviation 21.1
Change in Mean Visual Function Questionnaire (VFQ-25) Overall Composite	8.1 Scores on a scale Standard Deviation 10.6	5.5 Scores on a scale Standard Deviation 11.3	9.1 Scores on a scale Standard Deviation 15.5	10.0 Scores on a scale Standard Deviation 15.9
Change in Mean Visual Function Questionnaire (VFQ-25) General Vision	15.0 Scores on a scale Standard Deviation 16.7	9.5 Scores on a scale Standard Deviation 16.3	20.0 Scores on a scale Standard Deviation 17.7	13.6 Scores on a scale Standard Deviation 23.4
Change in Mean Visual Function Questionnaire (VFQ-25) Ocular Pain	5.3 Scores on a scale Standard Deviation 15.7	5.3 Scores on a scale Standard Deviation 13.8	4.2 Scores on a scale Standard Deviation 20.8	3.4 Scores on a scale Standard Deviation 15.0
Change in Mean Visual Function Questionnaire (VFQ-25) Near Activities	13.3 Scores on a scale Standard Deviation 18.9	10.8 Scores on a scale Standard Deviation 20.6	12.3 Scores on a scale Standard Deviation 20.5	12.3 Scores on a scale Standard Deviation 23.2
Change in Mean Visual Function Questionnaire (VFQ-25) Distance Activities	8.9 Scores on a scale Standard Deviation 17.5	5.6 Scores on a scale Standard Deviation 15.3	7.8 Scores on a scale Standard Deviation 18.3	8.3 Scores on a scale Standard Deviation 23.4
Change in Mean Visual Function Questionnaire (VFQ-25) Mental Health	10.2 Scores on a scale Standard Deviation 14.9	2.9 Scores on a scale Standard Deviation 20.4	10.7 Scores on a scale Standard Deviation 21.7	15.1 Scores on a scale Standard Deviation 18.3
Change in Mean Visual Function Questionnaire (VFQ-25) Role Difficulties	4.8 Scores on a scale Standard Deviation 26.8	10.6 Scores on a scale Standard Deviation 20.5	14.6 Scores on a scale Standard Deviation 29.9	24.4 Scores on a scale Standard Deviation 27.8
Change in Mean Visual Function Questionnaire (VFQ-25) Dependency	3.2 Scores on a scale Standard Deviation 9.2	0.4 Scores on a scale Standard Deviation 16.6	5.1 Scores on a scale Standard Deviation 16.7	4.4 Scores on a scale Standard Deviation 12.8
Change in Mean Visual Function Questionnaire (VFQ-25) Driving (BRVO n=44,31) (CRVO n=42,16)	11.7 Scores on a scale Standard Deviation 23.9	4.8 Scores on a scale Standard Deviation 21.3	14.2 Scores on a scale Standard Deviation 24.6	17.7 Scores on a scale Standard Deviation 25.1
Change in Mean Visual Function Questionnaire (VFQ-25) Color Vision(BRVO n=52,39)	0.5 Scores on a scale Standard Deviation 10.5	1.9 Scores on a scale Standard Deviation 10.6	0.4 Scores on a scale Standard Deviation 17.5	-1.1 Scores on a scale Standard Deviation 14.4
Change in Mean Visual Function Questionnaire (VFQ-25) Peripheral Vision(BRVO n=51,40)	10.3 Scores on a scale Standard Deviation 24.1	6.9 Scores on a scale Standard Deviation 23.3	11.7 Scores on a scale Standard Deviation 25.0	14.8 Scores on a scale Standard Deviation 22.7

SECONDARY outcome

Timeframe: Baseline, month 12

The SF-36 measures the impact of disease on overall quality of life and consists of eight subscales (physical function, pain, general and mental health, vitality, social function, physical and emotional health) which can be aggregated to derive a physical-component summary score and a mental-component summary score. Scores for each subscale range from 0 to 10, and the composite scores range from 0 to 100, with higher scores indicating better health. A positive change from Baseline score indicates improvement in quality of life.

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=60 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Change in SF-36 Summary Scores Physical Component(BRVO n=50,39) (CRVO n=58,20)	1.6 Score on a scale Standard Deviation 5.0	0.2 Score on a scale Standard Deviation 7.0	-1.1 Score on a scale Standard Deviation 8.2	1.3 Score on a scale Standard Deviation 7.2
Change in SF-36 Summary Scores Mental Component (BRVO n=50,39) (CRVO n=58,20)	3.3 Score on a scale Standard Deviation 9.7	2.1 Score on a scale Standard Deviation 13.2	2.1 Score on a scale Standard Deviation 9.3	2.4 Score on a scale Standard Deviation 12.4

SECONDARY outcome

Timeframe: Baseline, month 12

The Euro Quality of Life Questionnaire (EQ-5D) standardized instrument was utilized to measure health outcomes related to mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Participants self-rate their health on a visual, vertical analogue scale from 0 to 100 where the endpoints are labeled "Best imaginable health state" (100) and "worst imaginable health state" (0).

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=58 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=21 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Change in Euro Quality of Life Questionnaire (EQ-5D) VAS Summary Scores	3.3 Score on a scale Standard Deviation 15.2	2.6 Score on a scale Standard Deviation 16.9	1.5 Score on a scale Standard Deviation 16.4	0.2 Score on a scale Standard Deviation 20.4

SECONDARY outcome

Timeframe: 6 months

Time to the first retreatment

Outcome measures

Outcome measures
Measure	Ranibizumab (BRVO) n=52 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required.	Ranibizumab (CRVO) n=61 Participants Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 Participants A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Time to the First Retreatment of Both Treatment Arms	37 Days Interval 3.0 to 56.0	NA Days Interval 328.0 to Not calculable because \<50% of patients received re-treatment	62 Days Interval 5.0 to 67.0	NA Days Interval 309.0 to Not calculable because \<50% of patients received re-treatment

Adverse Events

Ranibizumab (BRVO)

Serious events: 2 serious events

Other events: 35 other events

Deaths: 0 deaths

Dexamethasone (BRVO)

Serious events: 3 serious events

Other events: 28 other events

Deaths: 0 deaths

Ranibizumab (CRVO)

Serious events: 6 serious events

Other events: 45 other events

Deaths: 0 deaths

Dexamethasone (CRVO)

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

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 (BRVO) n=52 participants at risk Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (BRVO) n=40 participants at risk A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required	Ranibizumab (CRVO) n=61 participants at risk Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Dexamethasone (CRVO) n=22 participants at risk A PRN re-treatment scheme will be applied for the Dexamethasone arm during this extension study, i.e. patients may receive an implant at V1E or later as needed. Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) Minimum period of 5 months in between implantations was required
Eye disorders GLAUCOMA (Fellow eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders GLAUCOMA (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders IRIS NEOVASCULARISATION (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders MACULAR OEDEMA (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders OCULAR ISCHAEMIC SYNDROME (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders RETINAL DETACHMENT (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	4.5% 1/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders VISUAL ACUITY REDUCED (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Eye disorders VITREOUS HAEMORRHAGE (Study eye)	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	4.5% 1/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Musculoskeletal and connective tissue disorders INTERVERTEBRAL DISC PROTRUSION	1.9% 1/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	2.5% 1/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Musculoskeletal and connective tissue disorders ROTATOR CUFF SYNDROME	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	2.5% 1/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) SQUAMOUS CELL CARCINOMA OF SKIN	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Nervous system disorders LUMBAR RADICULOPATHY	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	2.5% 1/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Psychiatric disorders SUBSTANCE ABUSE	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	1.6% 1/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Respiratory, thoracic and mediastinal disorders PULMONARY EMBOLISM	1.9% 1/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.
Skin and subcutaneous tissue disorders PSORIASIS	0.00% 0/52 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	2.5% 1/40 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/61 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.	0.00% 0/22 The Safety Set consisted of all patients from the safety sets of the respective core study who had received at least one application of study treatment and had at least one safety assessment during the extension study. Patients were analyzed according to treatment received.