Trial Outcomes & Findings for Efficacy and Safety of Ranibizumab Intravitreal Injections Versus Dexamethasone Intravitreal Implant in Patients With Central Retinal Vein Occlusion (CRVO) (NCT NCT01396083)

NCT ID: NCT01396083

Last Updated: 2016-09-27

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. 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 pproximately 20/20. An increased score indicates improvement in acuity

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

243 participants

Primary outcome timeframe

Baseline, month 6

Results posted on

2016-09-27

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
124
119
Overall Study
COMPLETED
113
72
Overall Study
NOT COMPLETED
11
47

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
28
Overall Study
Unsatisfactory therapeutic effect
2
13
Overall Study
Consent withdrawn
4
5
Overall Study
Protocol deviation(s)
0
1
Overall Study
Abnormal laboratory value(s)
1
0
Overall Study
Administrative problems
1
0
Overall Study
Lost to Follow-up
1
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ranibizumab
n=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Total
n=243 Participants
Total of all reporting groups
Age, Continuous
65.3 Years
STANDARD_DEVIATION 11.4 • n=5 Participants
66.9 Years
STANDARD_DEVIATION 12.4 • n=7 Participants
66.1 Years
STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male
Female
52 Participants
n=5 Participants
46 Participants
n=7 Participants
98 Participants
n=5 Participants
Sex: Female, Male
Male
72 Participants
n=5 Participants
73 Participants
n=7 Participants
145 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. 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 pproximately 20/20. An increased score indicates improvement in acuity

Outcome measures

Outcome measures
Measure
Ranibizumab
n=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Mean Average BCVA Change From Month 1 Through Month 6 to Baseline
14.6 Letters
Standard Deviation 11.8
4.8 Letters
Standard Deviation 16.2

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=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Mean BCVA Change at Month 6
14.78 Letters
Interval 11.24 to 18.32
-3.17 Letters
Interval -6.8 to 0.46

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 number 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=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters
Loss of ≥10 letters
4 Participants
35 Participants
Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters
Loss of ≥5 letters
5 Participants
40 Participants
Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters
Gain≥15 letters
73 Participants
22 Participants
Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters
Loss of ≥15 letters
1 Participants
31 Participants
Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters
Gain ≥10 letters
89 Participants
38 Participants
Number of Patients Gaining / Losing ≥ 15 / 10 / 5 Letters
Gain ≥5 letters
104 Participants
54 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=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 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
62 Time to event (Days)
Interval 56.0 to 91.0
98 Time to event (Days)
Interval 63.0 to
NA - insufficient number of participants with events

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=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Change Over Time in BCVA
Month 3
14.04 letters
Interval 10.92 to 17.16
4.99 letters
Interval 1.79 to 8.18
Change Over Time in BCVA
Month 4
12.76 letters
Interval 9.48 to 16.04
-1.73 letters
Interval -5.09 to 1.63
Change Over Time in BCVA
Month 5
13.57 letters
Interval 10.25 to 16.89
-2.92 letters
Interval -6.33 to 0.48
Change Over Time in BCVA
Month 6
14.78 letters
Interval 11.24 to 18.32
-3.17 letters
Interval -6.8 to 0.46
Change Over Time in BCVA
Month 1
9.77 letters
Interval 7.27 to 12.27
9.54 letters
Interval 6.98 to 12.1
Change Over Time in BCVA
Month 2
12.25 letters
Interval 9.59 to 14.91
11.04 letters
Interval 8.31 to 13.76

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=122 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 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)
-376.7 µm
Standard Deviation 274.9
-168.7 µm
Standard Deviation 288.3

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=121 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
6.0 Score on a scale
Standard Deviation 12.1
2.0 Score on a scale
Standard Deviation 10.9

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=116 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=113 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=116,113)
-0.7 Units on a scale
Standard Deviation 6.3
0.4 Units on a scale
Standard Deviation 6.6
Changes in the Quality of Life According to the Short Form (36) Health Survey (SF-36)Questionnaires
SF-36 mental component (n=116,113)
2.4 Units on a scale
Standard Deviation 8.7
0.4 Units on a scale
Standard Deviation 9.2

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=116 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=113 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
0.1 Units on a scale
Standard Deviation 13.2
2.0 Units on a scale
Standard Deviation 14.8

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 Internal Ocular Pressure (IOP) compared to baseline at any post-baseline visit.

Outcome measures

Outcome measures
Measure
Ranibizumab
n=124 Participants
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 Participants
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Increase Rate of the Internal Ocular Pressure (IOP ) : Patients With ≥10% Increase in IOP Compared to Baseline
94 Participants
105 Participants

Adverse Events

Ranibizumab

Serious events: 10 serious events
Other events: 77 other events
Deaths: 0 deaths

Dexamethasone

Serious events: 16 serious events
Other events: 99 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ranibizumab
n=124 participants at risk
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 participants at risk
Intravitreal implant as per commercial label (700 μg Dexamethasone; long acting release (LAR) over 6 months
Cardiac disorders
ANGINA PECTORIS
0.00%
0/124
0.84%
1/119
Cardiac disorders
ATRIAL FIBRILLATION
0.81%
1/124
0.84%
1/119
Cardiac disorders
CARDIAC FAILURE
0.00%
0/124
0.84%
1/119
Cardiac disorders
MITRAL VALVE INCOMPETENCE
0.00%
0/124
0.84%
1/119
Congenital, familial and genetic disorders
ADENOMATOUS POLYPOSIS COLI
0.81%
1/124
0.00%
0/119
Ear and labyrinth disorders
DEAFNESS
0.00%
0/124
0.84%
1/119
Eye disorders
CONJUNCTIVAL HYPERAEMIA (Study eye)
0.00%
0/124
0.84%
1/119
Eye disorders
CORNEAL OEDEMA (Study eye)
0.00%
0/124
0.84%
1/119
Eye disorders
EYE PAIN (Study eye)
0.00%
0/124
0.84%
1/119
Eye disorders
GLAUCOMA (Study eye)
0.00%
0/124
2.5%
3/119
Eye disorders
HYPHAEMA (Study eye)
0.00%
0/124
2.5%
3/119
Eye disorders
IRIS NEOVASCULARISATION (Study eye)
0.00%
0/124
3.4%
4/119
Eye disorders
MACULAR OEDEMA (Study eye)
0.81%
1/124
1.7%
2/119
Eye disorders
RETINAL ARTERY OCCLUSION (Study eye)
0.00%
0/124
0.84%
1/119
Eye disorders
RETINAL VEIN OCCLUSION (Study eye)
0.81%
1/124
0.84%
1/119
Eye disorders
VISUAL ACUITY REDUCED (Study eye)
0.00%
0/124
2.5%
3/119
Eye disorders
VITREOUS HAEMORRHAGE (Study eye)
0.00%
0/124
0.84%
1/119
Gastrointestinal disorders
ABDOMINAL HERNIA
0.00%
0/124
0.84%
1/119
Gastrointestinal disorders
COLITIS
0.00%
0/124
0.84%
1/119
Gastrointestinal disorders
GASTRODUODENAL ULCER
0.81%
1/124
0.00%
0/119
Gastrointestinal disorders
OESOPHAGEAL RUPTURE
0.81%
1/124
0.00%
0/119
Gastrointestinal disorders
UMBILICAL HERNIA
0.81%
1/124
0.00%
0/119
General disorders
ASTHENIA
0.81%
1/124
0.00%
0/119
General disorders
FATIGUE
0.81%
1/124
0.00%
0/119
Infections and infestations
CYSTITIS
0.81%
1/124
0.00%
0/119
Infections and infestations
DIVERTICULITIS
0.00%
0/124
0.84%
1/119
Infections and infestations
PNEUMONIA
0.81%
1/124
0.00%
0/119
Infections and infestations
SOFT TISSUE INFECTION
0.00%
0/124
0.84%
1/119
Injury, poisoning and procedural complications
UPPER LIMB FRACTURE
0.81%
1/124
0.00%
0/119
Injury, poisoning and procedural complications
WRIST FRACTURE
0.81%
1/124
0.00%
0/119
Investigations
INTRAOCULAR PRESSURE DECREASED (Study eye)
0.00%
0/124
0.84%
1/119
Investigations
INTRAOCULAR PRESSURE INCREASED (Study eye)
0.00%
0/124
0.84%
1/119
Investigations
PROSTATIC SPECIFIC ANTIGEN INCREASED
0.81%
1/124
0.00%
0/119
Investigations
WEIGHT DECREASED
0.81%
1/124
0.00%
0/119
Musculoskeletal and connective tissue disorders
BACK PAIN
0.00%
0/124
0.84%
1/119
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA OF COLON
0.00%
0/124
0.84%
1/119
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
GASTROINTESTINAL CARCINOMA
0.00%
0/124
0.84%
1/119
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
RENAL NEOPLASM
0.00%
0/124
0.84%
1/119
Nervous system disorders
HEADACHE
0.00%
0/124
0.84%
1/119
Nervous system disorders
RADIAL NERVE PALSY
0.00%
0/124
0.84%
1/119
Nervous system disorders
TRANSIENT ISCHAEMIC ATTACK
0.00%
0/124
1.7%
2/119
Reproductive system and breast disorders
PROSTATITIS
0.81%
1/124
0.00%
0/119
Vascular disorders
HYPERTENSION
0.00%
0/124
0.84%
1/119

Other adverse events

Other adverse events
Measure
Ranibizumab
n=124 participants at risk
Injections consisted of 0.5 mg/0.05 ml solution to be injected intravitreally
Dexamethasone
n=119 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)
4.8%
6/124
6.7%
8/119
Eye disorders
CONJUNCTIVAL HAEMORRHAGE (Study eye)
12.9%
16/124
10.9%
13/119
Eye disorders
DRY EYE (Fellow eye)
3.2%
4/124
0.84%
1/119
Eye disorders
DRY EYE (Study eye)
3.2%
4/124
3.4%
4/119
Eye disorders
EYE IRRITATION (Study eye)
3.2%
4/124
2.5%
3/119
Eye disorders
EYE PAIN (Study eye)
12.1%
15/124
11.8%
14/119
Eye disorders
FOREIGN BODY SENSATION IN EYES (Study eye)
4.8%
6/124
5.0%
6/119
Eye disorders
GLAUCOMA (Study eye)
0.00%
0/124
4.2%
5/119
Eye disorders
IRIS NEOVASCULARISATION (Study eye)
0.00%
0/124
4.2%
5/119
Eye disorders
LACRIMATION INCREASED (Study eye)
4.8%
6/124
6.7%
8/119
Eye disorders
MACULAR ISCHAEMIA (Study eye)
0.00%
0/124
2.5%
3/119
Eye disorders
MACULAR OEDEMA (Study eye)
10.5%
13/124
16.0%
19/119
Eye disorders
OCULAR HYPERAEMIA (Study eye)
11.3%
14/124
12.6%
15/119
Eye disorders
OCULAR HYPERTENSION (Study eye)
0.00%
0/124
5.0%
6/119
Eye disorders
OPTIC DISC VASCULAR DISORDER (Study eye)
4.0%
5/124
0.00%
0/119
Eye disorders
RETINAL EXUDATES (Study eye)
1.6%
2/124
3.4%
4/119
Eye disorders
RETINAL ISCHAEMIA (Study eye)
0.81%
1/124
5.0%
6/119
Eye disorders
RETINAL VASCULAR DISORDER (Study eye)
1.6%
2/124
4.2%
5/119
Eye disorders
VISUAL ACUITY REDUCED (Study eye)
6.5%
8/124
16.0%
19/119
Eye disorders
VISUAL IMPAIRMENT (Study eye)
1.6%
2/124
5.0%
6/119
Eye disorders
VITREOUS DETACHMENT (Study eye)
4.0%
5/124
2.5%
3/119
Eye disorders
VITREOUS FLOATERS (Study eye)
4.0%
5/124
9.2%
11/119
Gastrointestinal disorders
DIARRHOEA
4.8%
6/124
1.7%
2/119
Gastrointestinal disorders
NAUSEA
3.2%
4/124
2.5%
3/119
General disorders
PYREXIA
0.00%
0/124
2.5%
3/119
Infections and infestations
BRONCHITIS
0.81%
1/124
2.5%
3/119
Infections and infestations
NASOPHARYNGITIS
7.3%
9/124
10.1%
12/119
Infections and infestations
URINARY TRACT INFECTION
0.81%
1/124
3.4%
4/119
Investigations
BLOOD GLUCOSE INCREASED
3.2%
4/124
1.7%
2/119
Investigations
INTRAOCULAR PRESSURE INCREASED (Fellow eye)
0.00%
0/124
2.5%
3/119
Investigations
INTRAOCULAR PRESSURE INCREASED (Study eye)
5.6%
7/124
31.9%
38/119
Musculoskeletal and connective tissue disorders
ARTHRALGIA
1.6%
2/124
2.5%
3/119
Musculoskeletal and connective tissue disorders
BACK PAIN
5.6%
7/124
3.4%
4/119
Nervous system disorders
HEADACHE
5.6%
7/124
8.4%
10/119
Vascular disorders
HYPERTENSION
4.0%
5/124
2.5%
3/119
Vascular disorders
VASCULAR SHUNT (Study eye)
0.81%
1/124
2.5%
3/119

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