COMRADE-B: Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Branch Retinal Vein Occlusion (BRVO)

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01396057
• Collaborator: (none)
• Enrollment: 244
• Locations: 66
• Arms: 2
• Duration (Months): 23
• Patients Per Site: 3.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This clinical trial is designed to compare ranibizumab in comparison with Dexamethasone implant after 6 months of treatment. In the study arm Ranibizumab will be given monthly in a pro re nata scheme whereas the comparator Dexamethasone implant is given once at Month 0 with sham injections PRN afterwards.

Condition or Disease	Intervention/Treatment	Phase
Visual Impairment; Macular Edema; Branch Retinal Vein Occlusion	Drug: Ranibizumab; Other: Dexamethasone Implant; Other: Sham injection	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 244 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 6-month Multicenter, Randomized, Double-masked Phase IIIb-study Comparing the Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Visual Impairment Due to Macular Edema Following Branch Retinal Vein Occlusion (BRVO)
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Drug: Ranibizumab; Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally. Ranibizumab was formulated as a sterile solution aseptically filled in a sterile glass vial. It was suitable for single use only and the content of the vial was not allowed to be split
Sham Comparator: Dexamethasone Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months	Other: Dexamethasone Implant; Comparator Ozurdex® (dexamethasone) was formulated as a rod shaped implant to be inserted into the eye by an applicator. The implant as well as the respective applicator were suitable for single use only.; Other: Sham injection; Sham injection: Empty sterile syringes were provided so that masking could be maintained. Either empty syringes in the case of sham injections or pre-filled syringes in the case of ranibizumab injections were visible to the patient in the room of study drug administration

Outcome Measures

Primary Outcome Measures

1. Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline [Baseline, month 6]

   the average of the changes in BCVA (letters) from baseline to any post-baseline visit, i.e. the mean of six differences to baseline for the six post-baseline visits at month 1 to 6

Secondary Outcome Measures

1. Mean BCVA Change From Baseline to Endpoints Month 1 to Month 6 [Baseline, month 6]

   The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors

2. Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment [Baseline, 6 month]

   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 gained 15, 10 or 5 more letters of visual acuity at month 6 as compared with baseline

3. Time to Achieve a Significant Improvement ≥ 15 Letters [Baseline, month 6]

   The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts

4. Change Over Time in BCVA [baseline, month 6]

   The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors

5. Change Over Time of the Central Retinal Thickness (CRT) [Baseline, month 6]

   Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation

6. Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires [Baseline, month 6]

   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.

7. Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires [Baseline, month 6]

   SF-36 summary measures are norm-based scores with mean = 50 and SD = 10. Higher scores indicate better health

8. Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires [Baseline, month 6]

   The EQ-5D visual analog scale ranges from 0 to 100, 0 representing the worst and 100 the best imaginable health state.

9. Rate of the Internal Ocular Pressure (IOP) [Baseline, month 6]

   The proportion of patients with ≥ 10% increase in IOP compared to baseline at any post-baseline visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients diagnosed with visual impairment due to macular edema following BRVO

• Diagnosis of BRVO at maximum 6 months prior to Screening

• BCVA using ETDRS charts of 20/40 to 20/400 in the study eye

Exclusion Criteria:

• Media clarity, pupillary dilation and patient cooperation not sufficient for adequate fundus photographs

• Central retinal thickness (CRT) < 250 µm in the study eye

• Prior episode of RVO in the study eye

• Active formation of new vessels in the study eye

• Anti-VEGF-treatment in the study or the fellow eye 3 months prior to Baseline

• IOP ≥ 30mmHg or uncontrolled glaucoma; patients may be re-screened after 1 month if they have undergone glaucoma treatment

• Improvement of > 10 letters on BCVA between Screening and Baseline

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Praha 10		Czech Republic	100 34
2	Novartis Investigative Site	Augsburg		Germany	85155
3	Novartis Investigative Site	Bad Rothenfelde		Germany	49215
4	Novartis Investigative Site	Berlin		Germany	10713
5	Novartis Investigative Site	Berlin		Germany	13353
6	Novartis Investigative Site	Bochum		Germany	44791
7	Novartis Investigative Site	Bonn		Germany	53127
8	Novartis Investigative Site	Bremen		Germany	28209
9	Novartis Investigative Site	Chemnitz		Germany	09116
10	Novartis Investigative Site	Darmstadt		Germany	64298
11	Novartis Investigative Site	Dresden		Germany	01257
12	Novartis Investigative Site	Duesseldorf		Germany	40225
13	Novartis Investigative Site	Düsseldorf		Germany	40212
14	Novartis Investigative Site	Frankfurt		Germany	60318
15	Novartis Investigative Site	Freiburg i. Br		Germany	79106
16	Novartis Investigative Site	Glauchau		Germany	08371
17	Novartis Investigative Site	Göttingen		Germany	37075
18	Novartis Investigative Site	Hagen		Germany	58097
19	Novartis Investigative Site	Halle		Germany	06114
20	Novartis Investigative Site	Hamburg		Germany	20246
21	Novartis Investigative Site	Hamburg		Germany	22417
22	Novartis Investigative Site	Homburg		Germany	66421
23	Novartis Investigative Site	Ingolstadt		Germany	85049
24	Novartis Investigative Site	Karlsruhe		Germany	76133
25	Novartis Investigative Site	Karlsruhe		Germany	76199
26	Novartis Investigative Site	Kiel		Germany	24105
27	Novartis Investigative Site	Koeln		Germany	50935
28	Novartis Investigative Site	Leipzig		Germany	04103
29	Novartis Investigative Site	Ludwigshafen		Germany	67063
30	Novartis Investigative Site	Marburg		Germany	35039
31	Novartis Investigative Site	Minden		Germany	32427
32	Novartis Investigative Site	Muelheim		Germany	45468
33	Novartis Investigative Site	Muenster		Germany	48145
34	Novartis Investigative Site	Muenster		Germany	48149
35	Novartis Investigative Site	Munich		Germany	80336
36	Novartis Investigative Site	München		Germany	81675
37	Novartis Investigative Site	Recklinghausen		Germany	45657
38	Novartis Investigative Site	Regensburg		Germany	93042
39	Novartis Investigative Site	Sulzbach		Germany	66280
40	Novartis Investigative Site	Tübingen		Germany	72076
41	Novartis Investigative Site	Ulm		Germany	89075
42	Novartis Investigative Site	Wolfsburg		Germany	38442
43	Novartis Investigative Site	Würzburg		Germany	97080
44	Novartis Investigative Site	Budapest		Hungary	1083
45	Novartis Investigative Site	Debrecen		Hungary	4004
46	Novartis Investigative Site	Szeged		Hungary	H-6720
47	Novartis Investigative Site	Bydgoszcz		Poland
48	Novartis Investigative Site	Bytom		Poland	41-902
49	Novartis Investigative Site	Birmingham		United Kingdom	B152WB
50	Novartis Investigative Site	Birmingham		United Kingdom	B18 7QU
51	Novartis Investigative Site	Bradford		United Kingdom	BD9 6RJ
52	Novartis Investigative Site	Cheshire		United Kingdom	CW14QJ
53	Novartis Investigative Site	Colchester		United Kingdom	CO3 3NB
54	Novartis Investigative Site	Derby		United Kingdom	DE22 3NE
55	Novartis Investigative Site	Gloucester		United Kingdom	GL1 3NN
56	Novartis Investigative Site	Guildford, Surrey		United Kingdom	GU2 5XX
57	Novartis Investigative Site	Kent		United Kingdom	CT1 3NG
58	Novartis Investigative Site	Leeds		United Kingdom	LS9 7TF
59	Novartis Investigative Site	London		United Kingdom	SE1 7EH
60	Novartis Investigative Site	Manchester		United Kingdom	M13 9WH
61	Novartis Investigative Site	Middlesborough		United Kingdom	TS4 3BW
62	Novartis Investigative Site	Nottingham		United Kingdom	NG7 2UH
63	Novartis Investigative Site	Portsmouth		United Kingdom	PO6 3LY
64	Novartis Investigative Site	Rugby		United Kingdom	CV22 5PX
65	Novartis Investigative Site	Westcliff-on-Sea		United Kingdom	SS0 0RY
66	Novartis Investigative Site	York		United Kingdom	YO31 8HE

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01396057
• Other Study ID Numbers: CRFB002EDE17; 2011-001019-30
• First Posted: Jul 18, 2011
• Last Update Posted: Aug 7, 2014
• Last Verified: Aug 1, 2014

• Keywords provided by Novartis Pharmaceuticals: Visual impairment; macular edema; branch retinal vein occlusion; Dexamethasone implant; Ranibizumab
• Additional relevant MeSH terms: Vision Disorders; Vision, Low; Macular Edema; Retinal Vein Occlusion; Edema; Dexamethasone; Ranibizumab

Study Results

Participant Flow

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Period Title: Overall Study
STARTED	126	118
COMPLETED	115	100
NOT COMPLETED	11	18

Baseline Characteristics

Arm/Group Title	Ranibizumab	Dexamethasone	Total
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months	Total of all reporting groups
Overall Participants	126	118	244
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.7 (10.9)	65.6 (10.0)	65.6 (10.5)
Sex: Female, Male (Count of Participants)
Female	76 60.3%	57 48.3%	133 54.5%
Male	50 39.7%	61 51.7%	111 45.5%

Outcome Measures

1. Primary Outcome

Title	Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline
Description	the average of the changes in BCVA (letters) from baseline to any post-baseline visit, i.e. the mean of six differences to baseline for the six post-baseline visits at month 1 to 6
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Mean (Standard Deviation) [Letters]	14.9 (9.9)	10.1 (9.5)

2. Secondary Outcome

Title	Mean BCVA Change From Baseline to Endpoints Month 1 to Month 6
Description	The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Least Squares Mean (95% Confidence Interval) [Letters (EDTRS)]	16.18	8.10

3. Secondary Outcome

Title	Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Description	BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An 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 gained 15, 10 or 5 more letters of visual acuity at month 6 as compared with baseline
Time Frame	Baseline, 6 month

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Gain≥15 letters	77 61.1%	44 37.3%
Loss of ≥15 letters	0 0%	6 5.1%
Gain ≥10 letters	97 77%	63 53.4%
Loss of ≥10 letters	2 1.6%	8 6.8%
Gain ≥5 letters	108 85.7%	76 64.4%
Loss of ≥5 letters	4 3.2%	14 11.9%

4. Secondary Outcome

Title	Time to Achieve a Significant Improvement ≥ 15 Letters
Description	The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Median (95% Confidence Interval) [Time to event (Days)]	63	64

5. Secondary Outcome

Title	Change Over Time in BCVA
Description	The analysis was performed by an analysis of covariance (ANCOVA) model with average change in BCVA (letters) from Visit 1 through Visit 6 as dependent variable, and with the factors center, treatment and covariate baseline BCVA as predictors
Time Frame	baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Month 1	10.35	10.44
Month 2	13.84	12.62
Month 3	15.52	9.16
Month 4	14.39	8.59
Month 5	14.65	9.08
Month 6	16.18	8.10

6. Secondary Outcome

Title	Change Over Time of the Central Retinal Thickness (CRT)
Description	Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Mean (Standard Deviation) [µm]	-230.6 (169.3)	-112.3 (172.1)

7. Secondary Outcome

Title	Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires
Description	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.
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Following the intent-to-treat principle, patients were analyzed according to the treatment assigned

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Mean (Standard Deviation) [Score on a scale]	7.2 (10.2)	2.8 (12.6)

8. Secondary Outcome

Title	Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires
Description	SF-36 summary measures are norm-based scores with mean = 50 and SD = 10. Higher scores indicate better health
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. observed is only described in this analysis.

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
SF-36 physical component (n=121,114)	-1.1 (5.7)	-0.4 (5.7)
SF-36 mental component (n=121,114)	3.3 (9.2)	0.2 (9.6)

9. Secondary Outcome

Title	Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires
Description	The EQ-5D visual analog scale ranges from 0 to 100, 0 representing the worst and 100 the best imaginable health state.
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of all patients from the Randomized Set (RS) who had received at least one application of study treatment and had at least one post-baseline assessment for BCVA. Observed participants are only described in this analysis

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	123	118
Mean (Standard Deviation) [Units on a scale]	0.7 (15.2)	-2.4 (15.4)

10. Secondary Outcome

Title	Rate of the Internal Ocular Pressure (IOP)
Description	The proportion of patients with ≥ 10% increase in IOP compared to baseline at any post-baseline visit.
Time Frame	Baseline, month 6

Outcome Measure Data

Analysis Population Description

The Safety Set consisted of all patients from the RS who had received at least one application of study treatment and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. The statement that a patient had no adverse events also constituted a safety assessment

Arm/Group Title	Ranibizumab	Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally	Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Measure Participants	126	118
Number [Participants]	79 62.7%	106 89.8%

Adverse Events

Arm/Group Title	Ranibizumab		Dexamethasone
Arm/Group Description	Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally		Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
All Cause Mortality
	Ranibizumab		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ranibizumab		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/126 (5.6%)		9/118 (7.6%)
Cardiac disorders
ATRIOVENTRICULAR BLOCK SECOND DEGREE	1/126 (0.8%)		0/118 (0%)
BRADYARRHYTHMIA	1/126 (0.8%)		0/118 (0%)
Eye disorders
CONJUNCTIVITIS (Study eye)	0/126 (0%)		1/118 (0.8%)
OCULAR HYPERTENSION (Study eye)	0/126 (0%)		1/118 (0.8%)
Gastrointestinal disorders
ABDOMINAL HERNIA	0/126 (0%)		1/118 (0.8%)
CONSTIPATION	1/126 (0.8%)		0/118 (0%)
DYSPEPSIA	1/126 (0.8%)		0/118 (0%)
INGUINAL HERNIA	0/126 (0%)		1/118 (0.8%)
LARGE INTESTINE POLYP	1/126 (0.8%)		0/118 (0%)
RECTAL HAEMORRHAGE	0/126 (0%)		1/118 (0.8%)
UMBILICAL HERNIA	0/126 (0%)		1/118 (0.8%)
General disorders
FATIGUE	1/126 (0.8%)		0/118 (0%)
Infections and infestations
APPENDICITIS	0/126 (0%)		1/118 (0.8%)
BRONCHITIS	0/126 (0%)		1/118 (0.8%)
CELLULITIS (Study eye)	0/126 (0%)		1/118 (0.8%)
Injury, poisoning and procedural complications
FOOT FRACTURE	0/126 (0%)		1/118 (0.8%)
KIDNEY RUPTURE	0/126 (0%)		1/118 (0.8%)
PERIRENAL HAEMATOMA	0/126 (0%)		1/118 (0.8%)
ROAD TRAFFIC ACCIDENT	0/126 (0%)		1/118 (0.8%)
SPLENIC INJURY	0/126 (0%)		1/118 (0.8%)
Metabolism and nutrition disorders
TYPE 2 DIABETES MELLITUS	1/126 (0.8%)		0/118 (0%)
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION	1/126 (0.8%)		0/118 (0%)
RHEUMATIC DISORDER	1/126 (0.8%)		0/118 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER	1/126 (0.8%)		0/118 (0%)
RENAL CANCER	1/126 (0.8%)		0/118 (0%)
Renal and urinary disorders
DIABETIC NEPHROPATHY	1/126 (0.8%)		0/118 (0%)
NEPHROLITHIASIS	0/126 (0%)		1/118 (0.8%)
RENAL FAILURE	1/126 (0.8%)		0/118 (0%)
URETHRAL PROLAPSE	0/126 (0%)		1/118 (0.8%)
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM	1/126 (0.8%)		0/118 (0%)
SLEEP APNOEA SYNDROME	0/126 (0%)		1/118 (0.8%)
Vascular disorders
CIRCULATORY COLLAPSE	0/126 (0%)		1/118 (0.8%)
HYPERTENSION	0/126 (0%)		1/118 (0.8%)
Other (Not Including Serious) Adverse Events
	Ranibizumab		Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	71/126 (56.3%)		89/118 (75.4%)
Eye disorders
ABNORMAL SENSATION IN EYE (Study eye)	5/126 (4%)		3/118 (2.5%)
BLEPHARITIS (Fellow eye)	1/126 (0.8%)		3/118 (2.5%)
BLEPHARITIS (Study eye)	2/126 (1.6%)		5/118 (4.2%)
CATARACT (Study eye)	1/126 (0.8%)		4/118 (3.4%)
CONJUNCTIVAL HAEMORRHAGE (Study eye)	12/126 (9.5%)		14/118 (11.9%)
CONJUNCTIVAL IRRITATION (Study eye)	4/126 (3.2%)		4/118 (3.4%)
CONJUNCTIVITIS (Study eye)	4/126 (3.2%)		2/118 (1.7%)
EYE DISCHARGE (Study eye)	5/126 (4%)		5/118 (4.2%)
EYE IRRITATION (Fellow eye)	1/126 (0.8%)		3/118 (2.5%)
EYE IRRITATION (Study eye)	3/126 (2.4%)		6/118 (5.1%)
EYE PAIN (Study eye)	9/126 (7.1%)		13/118 (11%)
EYELID OEDEMA (Study eye)	0/126 (0%)		3/118 (2.5%)
FOREIGN BODY SENSATION IN EYES (Study eye)	8/126 (6.3%)		4/118 (3.4%)
GLAUCOMA (Study eye)	1/126 (0.8%)		3/118 (2.5%)
LACRIMATION INCREASED (Fellow eye)	2/126 (1.6%)		4/118 (3.4%)
LACRIMATION INCREASED (Study eye)	7/126 (5.6%)		4/118 (3.4%)
MACULAR OEDEMA (Study eye)	4/126 (3.2%)		7/118 (5.9%)
OCULAR DISCOMFORT (Study eye)	2/126 (1.6%)		8/118 (6.8%)
OCULAR HYPERAEMIA (Study eye)	16/126 (12.7%)		21/118 (17.8%)
OCULAR HYPERTENSION (Study eye)	0/126 (0%)		6/118 (5.1%)
RETINAL EXUDATES (Study eye)	7/126 (5.6%)		3/118 (2.5%)
VISION BLURRED (Study eye)	6/126 (4.8%)		2/118 (1.7%)
VISUAL ACUITY REDUCED (Study eye)	4/126 (3.2%)		6/118 (5.1%)
VITREOUS DETACHMENT (Study eye)	3/126 (2.4%)		7/118 (5.9%)
VITREOUS FLOATERS (Study eye)	3/126 (2.4%)		3/118 (2.5%)
Gastrointestinal disorders
VOMITING	0/126 (0%)		3/118 (2.5%)
Infections and infestations
CYSTITIS	4/126 (3.2%)		1/118 (0.8%)
LOWER RESPIRATORY TRACT INFECTION	3/126 (2.4%)		4/118 (3.4%)
NASOPHARYNGITIS	20/126 (15.9%)		21/118 (17.8%)
Injury, poisoning and procedural complications
FALL	6/126 (4.8%)		3/118 (2.5%)
Investigations
BLOOD GLUCOSE INCREASED	1/126 (0.8%)		4/118 (3.4%)
INTRAOCULAR PRESSURE INCREASED	3/126 (2.4%)		19/118 (16.1%)
INTRAOCULAR PRESSURE INCREASED (Study eye)	2/126 (1.6%)		17/118 (14.4%)
Musculoskeletal and connective tissue disorders
BACK PAIN	5/126 (4%)		6/118 (5.1%)
PAIN IN EXTREMITY	5/126 (4%)		1/118 (0.8%)
Nervous system disorders
HEADACHE	13/126 (10.3%)		11/118 (9.3%)
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	6/126 (4.8%)		3/118 (2.5%)
Vascular disorders
HYPERTENSION	7/126 (5.6%)		5/118 (4.2%)
VASCULAR SHUNT (Study eye)	4/126 (3.2%)		0/118 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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