Trial Outcomes & Findings for Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Branch Retinal Vein Occlusion (BRVO) (NCT NCT01396057)

NCT ID: NCT01396057

Last Updated: 2014-08-07

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

244 participants

Primary outcome timeframe

Baseline, month 6

Results posted on

2014-08-07

Participant Flow

Participant milestones

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

Reasons for withdrawal

Reasons for withdrawal
Measure
Ranibizumab
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Overall Study
Adverse Event
2
6
Overall Study
Unsatisfactory therapeutic effect
2
6
Overall Study
Protocol deviation
4
4
Overall Study
Consent withdrawn
3
2

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Total
n=244 Participants
Total of all reporting groups
Age, Continuous
65.7 Years
STANDARD_DEVIATION 10.9 • n=5 Participants
65.6 Years
STANDARD_DEVIATION 10.0 • n=7 Participants
65.6 Years
STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male
Female
76 Participants
n=5 Participants
57 Participants
n=7 Participants
133 Participants
n=5 Participants
Sex: Female, Male
Male
50 Participants
n=5 Participants
61 Participants
n=7 Participants
111 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Mean Average Best Corrected Visual Acuity (BCVA) Change From Month 1 Through Month 6 to Baseline
14.9 Letters
Standard Deviation 9.9
10.1 Letters
Standard Deviation 9.5

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Mean BCVA Change From Baseline to Endpoints Month 1 to Month 6
16.18 Letters (EDTRS)
Interval 14.04 to 18.32
8.10 Letters (EDTRS)
Interval 5.79 to 10.4

SECONDARY outcome

Timeframe: Baseline, 6 month

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Gain≥15 letters
77 Participants
44 Participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Loss of ≥15 letters
0 Participants
6 Participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Gain ≥10 letters
97 Participants
63 Participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Loss of ≥10 letters
2 Participants
8 Participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Gain ≥5 letters
108 Participants
76 Participants
Percentage of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters After 6 Month Treatment
Loss of ≥5 letters
4 Participants
14 Participants

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Time to Achieve a Significant Improvement ≥ 15 Letters
63 Time to event (Days)
Interval 56.0 to 84.0
64 Time to event (Days)
Interval 59.0 to 126.0

SECONDARY outcome

Timeframe: baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Change Over Time in BCVA
Month 2
13.84 Letters
Interval 12.04 to 15.64
12.62 Letters
Interval 10.69 to 14.56
Change Over Time in BCVA
Month 3
15.52 Letters
Interval 13.44 to 17.59
9.16 Letters
Interval 6.92 to 11.39
Change Over Time in BCVA
Month 6
16.18 Letters
Interval 14.04 to 18.32
8.10 Letters
Interval 5.79 to 10.4
Change Over Time in BCVA
Month 1
10.35 Letters
Interval 8.53 to 12.17
10.44 Letters
Interval 8.48 to 12.4
Change Over Time in BCVA
Month 4
14.39 Letters
Interval 12.38 to 16.41
8.59 Letters
Interval 6.42 to 10.76
Change Over Time in BCVA
Month 5
14.65 Letters
Interval 12.52 to 16.78
9.08 Letters
Interval 6.79 to 11.37

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Change Over Time of the Central Retinal Thickness (CRT)
-230.6 µm
Standard Deviation 169.3
-112.3 µm
Standard Deviation 172.1

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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

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
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Changes in the Quality of Life According to the National Eye Institute Visual Function Questionnaire (NEI-VFQ 25) Questionnaires
7.2 Score on a scale
Standard Deviation 10.2
2.8 Score on a scale
Standard Deviation 12.6

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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.

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires
SF-36 physical component (n=121,114)
-1.1 Units on a scale
Standard Deviation 5.7
-0.4 Units on a scale
Standard Deviation 5.7
Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires
SF-36 mental component (n=121,114)
3.3 Units on a scale
Standard Deviation 9.2
0.2 Units on a scale
Standard Deviation 9.6

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=123 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Changes in the Quality of Life According to Euro Quality of Life (EQ-5D) Questionnaires
0.7 Units on a scale
Standard Deviation 15.2
-2.4 Units on a scale
Standard Deviation 15.4

SECONDARY outcome

Timeframe: Baseline, month 6

Population: 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

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

Outcome measures

Outcome measures
Measure
Ranibizumab
n=126 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Rate of the Internal Ocular Pressure (IOP)
79 Participants
106 Participants

Adverse Events

Ranibizumab

Serious events: 7 serious events
Other events: 71 other events
Deaths: 0 deaths

Dexamethasone

Serious events: 9 serious events
Other events: 89 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ranibizumab
n=126 participants at risk
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 participants at risk
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Cardiac disorders
ATRIOVENTRICULAR BLOCK SECOND DEGREE
0.79%
1/126
0.00%
0/118
Cardiac disorders
BRADYARRHYTHMIA
0.79%
1/126
0.00%
0/118
Eye disorders
CONJUNCTIVITIS (Study eye)
0.00%
0/126
0.85%
1/118
Eye disorders
OCULAR HYPERTENSION (Study eye)
0.00%
0/126
0.85%
1/118
Gastrointestinal disorders
ABDOMINAL HERNIA
0.00%
0/126
0.85%
1/118
Gastrointestinal disorders
CONSTIPATION
0.79%
1/126
0.00%
0/118
Gastrointestinal disorders
DYSPEPSIA
0.79%
1/126
0.00%
0/118
Gastrointestinal disorders
INGUINAL HERNIA
0.00%
0/126
0.85%
1/118
Gastrointestinal disorders
LARGE INTESTINE POLYP
0.79%
1/126
0.00%
0/118
Gastrointestinal disorders
RECTAL HAEMORRHAGE
0.00%
0/126
0.85%
1/118
Gastrointestinal disorders
UMBILICAL HERNIA
0.00%
0/126
0.85%
1/118
General disorders
FATIGUE
0.79%
1/126
0.00%
0/118
Infections and infestations
APPENDICITIS
0.00%
0/126
0.85%
1/118
Infections and infestations
BRONCHITIS
0.00%
0/126
0.85%
1/118
Infections and infestations
CELLULITIS (Study eye)
0.00%
0/126
0.85%
1/118
Injury, poisoning and procedural complications
FOOT FRACTURE
0.00%
0/126
0.85%
1/118
Injury, poisoning and procedural complications
KIDNEY RUPTURE
0.00%
0/126
0.85%
1/118
Injury, poisoning and procedural complications
PERIRENAL HAEMATOMA
0.00%
0/126
0.85%
1/118
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
0.00%
0/126
0.85%
1/118
Injury, poisoning and procedural complications
SPLENIC INJURY
0.00%
0/126
0.85%
1/118
Metabolism and nutrition disorders
TYPE 2 DIABETES MELLITUS
0.79%
1/126
0.00%
0/118
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC PROTRUSION
0.79%
1/126
0.00%
0/118
Musculoskeletal and connective tissue disorders
RHEUMATIC DISORDER
0.79%
1/126
0.00%
0/118
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
PROSTATE CANCER
0.79%
1/126
0.00%
0/118
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL CANCER
0.79%
1/126
0.00%
0/118
Renal and urinary disorders
DIABETIC NEPHROPATHY
0.79%
1/126
0.00%
0/118
Renal and urinary disorders
NEPHROLITHIASIS
0.00%
0/126
0.85%
1/118
Renal and urinary disorders
RENAL FAILURE
0.79%
1/126
0.00%
0/118
Renal and urinary disorders
URETHRAL PROLAPSE
0.00%
0/126
0.85%
1/118
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM
0.79%
1/126
0.00%
0/118
Respiratory, thoracic and mediastinal disorders
SLEEP APNOEA SYNDROME
0.00%
0/126
0.85%
1/118
Vascular disorders
CIRCULATORY COLLAPSE
0.00%
0/126
0.85%
1/118
Vascular disorders
HYPERTENSION
0.00%
0/126
0.85%
1/118

Other adverse events

Other adverse events
Measure
Ranibizumab
n=126 participants at risk
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=118 participants at risk
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Eye disorders
ABNORMAL SENSATION IN EYE (Study eye)
4.0%
5/126
2.5%
3/118
Eye disorders
BLEPHARITIS (Fellow eye)
0.79%
1/126
2.5%
3/118
Eye disorders
BLEPHARITIS (Study eye)
1.6%
2/126
4.2%
5/118
Eye disorders
CATARACT (Study eye)
0.79%
1/126
3.4%
4/118
Eye disorders
CONJUNCTIVAL HAEMORRHAGE (Study eye)
9.5%
12/126
11.9%
14/118
Eye disorders
CONJUNCTIVAL IRRITATION (Study eye)
3.2%
4/126
3.4%
4/118
Eye disorders
CONJUNCTIVITIS (Study eye)
3.2%
4/126
1.7%
2/118
Eye disorders
EYE DISCHARGE (Study eye)
4.0%
5/126
4.2%
5/118
Eye disorders
EYE IRRITATION (Fellow eye)
0.79%
1/126
2.5%
3/118
Eye disorders
EYE IRRITATION (Study eye)
2.4%
3/126
5.1%
6/118
Eye disorders
EYE PAIN (Study eye)
7.1%
9/126
11.0%
13/118
Eye disorders
EYELID OEDEMA (Study eye)
0.00%
0/126
2.5%
3/118
Eye disorders
FOREIGN BODY SENSATION IN EYES (Study eye)
6.3%
8/126
3.4%
4/118
Eye disorders
GLAUCOMA (Study eye)
0.79%
1/126
2.5%
3/118
Eye disorders
LACRIMATION INCREASED (Fellow eye)
1.6%
2/126
3.4%
4/118
Eye disorders
LACRIMATION INCREASED (Study eye)
5.6%
7/126
3.4%
4/118
Eye disorders
MACULAR OEDEMA (Study eye)
3.2%
4/126
5.9%
7/118
Eye disorders
OCULAR DISCOMFORT (Study eye)
1.6%
2/126
6.8%
8/118
Eye disorders
OCULAR HYPERAEMIA (Study eye)
12.7%
16/126
17.8%
21/118
Eye disorders
OCULAR HYPERTENSION (Study eye)
0.00%
0/126
5.1%
6/118
Eye disorders
RETINAL EXUDATES (Study eye)
5.6%
7/126
2.5%
3/118
Eye disorders
VISION BLURRED (Study eye)
4.8%
6/126
1.7%
2/118
Eye disorders
VISUAL ACUITY REDUCED (Study eye)
3.2%
4/126
5.1%
6/118
Eye disorders
VITREOUS DETACHMENT (Study eye)
2.4%
3/126
5.9%
7/118
Eye disorders
VITREOUS FLOATERS (Study eye)
2.4%
3/126
2.5%
3/118
Gastrointestinal disorders
VOMITING
0.00%
0/126
2.5%
3/118
Infections and infestations
CYSTITIS
3.2%
4/126
0.85%
1/118
Infections and infestations
LOWER RESPIRATORY TRACT INFECTION
2.4%
3/126
3.4%
4/118
Infections and infestations
NASOPHARYNGITIS
15.9%
20/126
17.8%
21/118
Injury, poisoning and procedural complications
FALL
4.8%
6/126
2.5%
3/118
Investigations
BLOOD GLUCOSE INCREASED
0.79%
1/126
3.4%
4/118
Investigations
INTRAOCULAR PRESSURE INCREASED
2.4%
3/126
16.1%
19/118
Investigations
INTRAOCULAR PRESSURE INCREASED (Study eye)
1.6%
2/126
14.4%
17/118
Musculoskeletal and connective tissue disorders
BACK PAIN
4.0%
5/126
5.1%
6/118
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
4.0%
5/126
0.85%
1/118
Nervous system disorders
HEADACHE
10.3%
13/126
9.3%
11/118
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
4.8%
6/126
2.5%
3/118
Vascular disorders
HYPERTENSION
5.6%
7/126
4.2%
5/118
Vascular disorders
VASCULAR SHUNT (Study eye)
3.2%
4/126
0.00%
0/118

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

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

Restriction type: OTHER