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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01396057
Recruitment Status : Completed
First Posted : July 18, 2011
Results First Posted : July 16, 2014
Last Update Posted : August 7, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Visual Impairment
Macular Edema
Branch Retinal Vein Occlusion
Interventions Drug: Ranibizumab
Other: Dexamethasone Implant
Other: Sham injection
Enrollment 244
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ranibizumab Dexamethasone
Hide 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
Reason Not Completed
Adverse Event             2             6
Unsatisfactory therapeutic effect             2             6
Protocol deviation             4             4
Consent withdrawn             3             2
Arm/Group Title Ranibizumab Dexamethasone Total
Hide 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 Number of Baseline Participants 126 118 244
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 126 participants 118 participants 244 participants
65.7  (10.9) 65.6  (10.0) 65.6  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 118 participants 244 participants
Female
76
  60.3%
57
  48.3%
133
  54.5%
Male
50
  39.7%
61
  51.7%
111
  45.5%
1.Primary Outcome
Title Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Letters (EDTRS)
16.18
(14.04 to 18.32)
8.10
(5.79 to 10.40)
3.Secondary Outcome
Title Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Measure Type: Number
Unit of Measure: Participants
Gain≥15 letters 77 44
Loss of ≥15 letters 0 6
Gain ≥10 letters 97 63
Loss of ≥10 letters 2 8
Gain ≥5 letters 108 76
Loss of ≥5 letters 4 14
4.Secondary Outcome
Title Time to Achieve a Significant Improvement ≥ 15 Letters
Hide Description The time was analyzed by the Kaplan-Maier-Method, adjusting the calculation for dropouts
Time Frame Baseline, month 6
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Median (95% Confidence Interval)
Unit of Measure: Time to event (Days)
63
(56 to 84)
64
(59 to 126)
5.Secondary Outcome
Title Change Over Time in BCVA
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Letters
Month 1
10.35
(8.53 to 12.17)
10.44
(8.48 to 12.40)
Month 2
13.84
(12.04 to 15.64)
12.62
(10.69 to 14.56)
Month 3
15.52
(13.44 to 17.59)
9.16
(6.92 to 11.39)
Month 4
14.39
(12.38 to 16.41)
8.59
(6.42 to 10.76)
Month 5
14.65
(12.52 to 16.78)
9.08
(6.79 to 11.37)
Month 6
16.18
(14.04 to 18.32)
8.10
(5.79 to 10.40)
6.Secondary Outcome
Title Change Over Time of the Central Retinal Thickness (CRT)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Mean (Standard Deviation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Mean (Standard Deviation)
Unit of Measure: Units on a scale
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 123 118
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.7  (15.2) -2.4  (15.4)
10.Secondary Outcome
Title Rate of the Internal Ocular Pressure (IOP)
Hide Description The proportion of patients with ≥ 10% increase in IOP compared to baseline at any post-baseline visit.
Time Frame Baseline, month 6
Hide Outcome Measure Data
Hide 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
Hide 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
Overall Number of Participants Analyzed 126 118
Measure Type: Number
Unit of Measure: Participants
79 106
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ranibizumab Dexamethasone
Hide 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 (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Ranibizumab Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   7/126 (5.56%)   9/118 (7.63%) 
Cardiac disorders     
ATRIOVENTRICULAR BLOCK SECOND DEGREE † 1  1/126 (0.79%)  0/118 (0.00%) 
BRADYARRHYTHMIA † 1  1/126 (0.79%)  0/118 (0.00%) 
Eye disorders     
CONJUNCTIVITIS (Study eye) † 1  0/126 (0.00%)  1/118 (0.85%) 
OCULAR HYPERTENSION (Study eye) † 1  0/126 (0.00%)  1/118 (0.85%) 
Gastrointestinal disorders     
ABDOMINAL HERNIA † 1  0/126 (0.00%)  1/118 (0.85%) 
CONSTIPATION † 1  1/126 (0.79%)  0/118 (0.00%) 
DYSPEPSIA † 1  1/126 (0.79%)  0/118 (0.00%) 
INGUINAL HERNIA † 1  0/126 (0.00%)  1/118 (0.85%) 
LARGE INTESTINE POLYP † 1  1/126 (0.79%)  0/118 (0.00%) 
RECTAL HAEMORRHAGE † 1  0/126 (0.00%)  1/118 (0.85%) 
UMBILICAL HERNIA † 1  0/126 (0.00%)  1/118 (0.85%) 
General disorders     
FATIGUE † 1  1/126 (0.79%)  0/118 (0.00%) 
Infections and infestations     
APPENDICITIS † 1  0/126 (0.00%)  1/118 (0.85%) 
BRONCHITIS † 1  0/126 (0.00%)  1/118 (0.85%) 
CELLULITIS (Study eye) † 1  0/126 (0.00%)  1/118 (0.85%) 
Injury, poisoning and procedural complications     
FOOT FRACTURE † 1  0/126 (0.00%)  1/118 (0.85%) 
KIDNEY RUPTURE † 1  0/126 (0.00%)  1/118 (0.85%) 
PERIRENAL HAEMATOMA † 1  0/126 (0.00%)  1/118 (0.85%) 
ROAD TRAFFIC ACCIDENT † 1  0/126 (0.00%)  1/118 (0.85%) 
SPLENIC INJURY † 1  0/126 (0.00%)  1/118 (0.85%) 
Metabolism and nutrition disorders     
TYPE 2 DIABETES MELLITUS † 1  1/126 (0.79%)  0/118 (0.00%) 
Musculoskeletal and connective tissue disorders     
INTERVERTEBRAL DISC PROTRUSION † 1  1/126 (0.79%)  0/118 (0.00%) 
RHEUMATIC DISORDER † 1  1/126 (0.79%)  0/118 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
PROSTATE CANCER † 1  1/126 (0.79%)  0/118 (0.00%) 
RENAL CANCER † 1  1/126 (0.79%)  0/118 (0.00%) 
Renal and urinary disorders     
DIABETIC NEPHROPATHY † 1  1/126 (0.79%)  0/118 (0.00%) 
NEPHROLITHIASIS † 1  0/126 (0.00%)  1/118 (0.85%) 
RENAL FAILURE † 1  1/126 (0.79%)  0/118 (0.00%) 
URETHRAL PROLAPSE † 1  0/126 (0.00%)  1/118 (0.85%) 
Respiratory, thoracic and mediastinal disorders     
PULMONARY EMBOLISM † 1  1/126 (0.79%)  0/118 (0.00%) 
SLEEP APNOEA SYNDROME † 1  0/126 (0.00%)  1/118 (0.85%) 
Vascular disorders     
CIRCULATORY COLLAPSE † 1  0/126 (0.00%)  1/118 (0.85%) 
HYPERTENSION † 1  0/126 (0.00%)  1/118 (0.85%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2.5%
Ranibizumab Dexamethasone
Affected / at Risk (%) Affected / at Risk (%)
Total   71/126 (56.35%)   89/118 (75.42%) 
Eye disorders     
ABNORMAL SENSATION IN EYE (Study eye) † 1  5/126 (3.97%)  3/118 (2.54%) 
BLEPHARITIS (Fellow eye) † 1  1/126 (0.79%)  3/118 (2.54%) 
BLEPHARITIS (Study eye) † 1  2/126 (1.59%)  5/118 (4.24%) 
CATARACT (Study eye) † 1  1/126 (0.79%)  4/118 (3.39%) 
CONJUNCTIVAL HAEMORRHAGE (Study eye) † 1  12/126 (9.52%)  14/118 (11.86%) 
CONJUNCTIVAL IRRITATION (Study eye) † 1  4/126 (3.17%)  4/118 (3.39%) 
CONJUNCTIVITIS (Study eye) † 1  4/126 (3.17%)  2/118 (1.69%) 
EYE DISCHARGE (Study eye) † 1  5/126 (3.97%)  5/118 (4.24%) 
EYE IRRITATION (Fellow eye) † 1  1/126 (0.79%)  3/118 (2.54%) 
EYE IRRITATION (Study eye) † 1  3/126 (2.38%)  6/118 (5.08%) 
EYE PAIN (Study eye) † 1  9/126 (7.14%)  13/118 (11.02%) 
EYELID OEDEMA (Study eye) † 1  0/126 (0.00%)  3/118 (2.54%) 
FOREIGN BODY SENSATION IN EYES (Study eye) † 1  8/126 (6.35%)  4/118 (3.39%) 
GLAUCOMA (Study eye) † 1  1/126 (0.79%)  3/118 (2.54%) 
LACRIMATION INCREASED (Fellow eye) † 1  2/126 (1.59%)  4/118 (3.39%) 
LACRIMATION INCREASED (Study eye) † 1  7/126 (5.56%)  4/118 (3.39%) 
MACULAR OEDEMA (Study eye) † 1  4/126 (3.17%)  7/118 (5.93%) 
OCULAR DISCOMFORT (Study eye) † 1  2/126 (1.59%)  8/118 (6.78%) 
OCULAR HYPERAEMIA (Study eye) † 1  16/126 (12.70%)  21/118 (17.80%) 
OCULAR HYPERTENSION (Study eye) † 1  0/126 (0.00%)  6/118 (5.08%) 
RETINAL EXUDATES (Study eye) † 1  7/126 (5.56%)  3/118 (2.54%) 
VISION BLURRED (Study eye) † 1  6/126 (4.76%)  2/118 (1.69%) 
VISUAL ACUITY REDUCED (Study eye) † 1  4/126 (3.17%)  6/118 (5.08%) 
VITREOUS DETACHMENT (Study eye) † 1  3/126 (2.38%)  7/118 (5.93%) 
VITREOUS FLOATERS (Study eye) † 1  3/126 (2.38%)  3/118 (2.54%) 
Gastrointestinal disorders     
VOMITING † 1  0/126 (0.00%)  3/118 (2.54%) 
Infections and infestations     
CYSTITIS † 1  4/126 (3.17%)  1/118 (0.85%) 
LOWER RESPIRATORY TRACT INFECTION † 1  3/126 (2.38%)  4/118 (3.39%) 
NASOPHARYNGITIS † 1  20/126 (15.87%)  21/118 (17.80%) 
Injury, poisoning and procedural complications     
FALL † 1  6/126 (4.76%)  3/118 (2.54%) 
Investigations     
BLOOD GLUCOSE INCREASED † 1  1/126 (0.79%)  4/118 (3.39%) 
INTRAOCULAR PRESSURE INCREASED † 1  3/126 (2.38%)  19/118 (16.10%) 
INTRAOCULAR PRESSURE INCREASED (Study eye) † 1  2/126 (1.59%)  17/118 (14.41%) 
Musculoskeletal and connective tissue disorders     
BACK PAIN † 1  5/126 (3.97%)  6/118 (5.08%) 
PAIN IN EXTREMITY † 1  5/126 (3.97%)  1/118 (0.85%) 
Nervous system disorders     
HEADACHE † 1  13/126 (10.32%)  11/118 (9.32%) 
Respiratory, thoracic and mediastinal disorders     
OROPHARYNGEAL PAIN † 1  6/126 (4.76%)  3/118 (2.54%) 
Vascular disorders     
HYPERTENSION † 1  7/126 (5.56%)  5/118 (4.24%) 
VASCULAR SHUNT (Study eye) † 1  4/126 (3.17%)  0/118 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01396057    
Other Study ID Numbers: CRFB002EDE17
2011-001019-30 ( EudraCT Number )
First Submitted: July 14, 2011
First Posted: July 18, 2011
Results First Submitted: June 13, 2014
Results First Posted: July 16, 2014
Last Update Posted: August 7, 2014