Trial Outcomes & Findings for Ranibizumab Intravitreal Injections in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion (NCT NCT01535261)

NCT ID: NCT01535261

Last Updated: 2016-10-27

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

357 participants

Primary outcome timeframe

Baseline to month 12

Results posted on

2016-10-27

Participant Flow

No data were excluded from the Full Analysis Set (FAS )analyses because of protocol deviations.

Participant milestones

Participant milestones
Measure
Ranibizumab Arm
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Study
STARTED
357
Overall Study
COMPLETED
307
Overall Study
NOT COMPLETED
50

Reasons for withdrawal

Reasons for withdrawal
Measure
Ranibizumab Arm
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Study
Physician Decision
8
Overall Study
Protocol Violation
3
Overall Study
Death
5
Overall Study
Lost to Follow-up
8
Overall Study
Withdrawal by Subject
14
Overall Study
Adverse Event
12

Baseline Characteristics

Ranibizumab Intravitreal Injections in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal Vein Occlusion

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Ranibizumab Arm
n=357 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Age, Continuous
65.5 Years
STANDARD_DEVIATION 12.68 • n=5 Participants
Sex: Female, Male
Female
128 Participants
n=5 Participants
Sex: Female, Male
Male
229 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline to month 12

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. One patient was excluded from the FAS for not having ≥ 1 post-baseline study eye VA assessment.

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

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=356 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Mean Change in Best Corrected Visual Acuity (BCVA) at Month 12 Compared to Baseline
12.3 Letters
Standard Deviation 16.72

SECONDARY outcome

Timeframe: Baseline to Month 24

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. One patient was excluded from the FAS for not having ≥ 1 post-baseline study eye VA assessment.

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

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=356 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Mean Change in Best Corrected Visual Acuity (BCVA) at Month 24 Compared to Baseline
12.1 Letters
Standard Deviation 18.60

SECONDARY outcome

Timeframe: Baseline and Month 1 to 12 or Month 24

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. One patient was excluded from the FAS for not having ≥ 1 post-baseline study eye VA assessment.

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. Mean Average Change: for each patient, first average change is calculated as the average of the changes from baseline to Month 1 over Month 12 (or Month 24). Then, mean average change is calculated as the average of average changes across all patients.

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=356 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Mean Average Change in Best Corrected Visual Acuity (BCVA From Baseline Month 12 and Month 24
Month 12
11.8 letters
Standard Deviation 12.44
Mean Average Change in Best Corrected Visual Acuity (BCVA From Baseline Month 12 and Month 24
Month 24
12.1 letters
Standard Deviation 14.20

SECONDARY outcome

Timeframe: Month 12 and Month 24

Population: Full analysis set with use of LOCF consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. The number of patients shown was with a value at treatment interruption and an average for the post treatment interruption visits.

Best-Corrected Visual Acuity (BCVA) letters was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart while participants were in a sitting position at a testing distance of 4 meters. The range of ETDRS is 0 to 100 letters. Stability in visual acuity after treatment interruption indicates longer duration of the drug efficacy

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=356 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Mean Average Change in BCVA From First Treatment Interruption (Due to BCVA Stabilization) to Month 12 and Month 24
Month 12 (n=310)
-2.7 Letters
Standard Deviation 8.04
Mean Average Change in BCVA From First Treatment Interruption (Due to BCVA Stabilization) to Month 12 and Month 24
Month 24 (n=331)
-2.5 Letters
Standard Deviation 8.95

SECONDARY outcome

Timeframe: Month 12 and Month 24

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. No data were excluded from the FAS analyses because of protocol deviations.

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 increased score indicates improvement in acuity. This outcome assessed the number of participants who had improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 letters of visual acuity at month 12 as compared with baseline

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=356 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 1 (Month 12)
296 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 5 (Month 12)
275 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 10 (Month 12)
227 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 15 (Month 12)
175 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 30 (Month 12)
32 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 1 (Month 24)
290 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 5 (Month 24)
265 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 10 (Month 24)
224 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 15 (Month 24)
175 Letters
Number of Patients With a BCVA Improvement of ≥1, ≥5, ≥10, ≥15, and ≥30 Letters From Baseline to Month 12 and Month 24 in the Study Eye
BCVA improvement of >= 30 (Month 24)
44 Letters

SECONDARY outcome

Timeframe: Month 12 and Month 24

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. No data were excluded from the FAS analyses because of protocol deviations.

Best Corrected Visual Acuity (BCVA) was measured using Early Treatment Diabetic Retinopathy Study (ETDRS)-like chart at baseline and month 12 while participants were in a sitting position at a testing distance of 4 meters. The range of EDTRS is 0 to 100 letters. BCVA above 73 letters at month 12 and month 24 indicates a positive outcome.

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=356 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 and Month 24
Month 12
169 Letters
Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 and Month 24
Month 24
161 Letters

SECONDARY outcome

Timeframe: Baseline, Month 12 and Month 24

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. No data were excluded from the FAS analyses because of protocol deviations.

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 Arm
n=347 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Mean Change in Central Reading Center (CRC)-Assessed Central Subfield Thickness (CSFT) From Month 12 and Month 24 Compared to Baseline
Change from Baseline at Month 12
-335.7 Microns
Standard Deviation 285.02
Mean Change in Central Reading Center (CRC)-Assessed Central Subfield Thickness (CSFT) From Month 12 and Month 24 Compared to Baseline
Change from Baseline at Month 24
-349.1 Microns
Standard Deviation 275.35

SECONDARY outcome

Timeframe: Month 12 and Month 24

Population: The Full analysis set (FAS) with use of Last Observation Carried Forward (LOCF) consisted of all patients who received at least 1 administration of study treatment and had at least 1 post-baseline assessment for BCVA in the study eye. The number of patients shown was with a value for both baseline and the post-baseline visit.

The survey consists of 25 items representing 11 vision related constructs (general vision, ocular pain, near activities, distance activities, social functioning, mental health, role difficulties, dependency, driving, color vision, peripheral vision) plus a single-item general health rating question. The score of each individual question ranges from 0 (worst) to 100 which indicates the best possible response. The composite score and score of each of each construct also range from 0 to 100 as they are calculated as total scores divided by the number of questions. The higher the values of total scores represent better outcome. Scores per visit and of the change descriptively by visit.

Outcome measures

Outcome measures
Measure
Ranibizumab Arm
n=350 Participants
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Mean Change in Patient-reported Outcomes in NEI-VFQ-25 Composite and Subscale Scores at Month 12 and Month 24 Compared to Baseline
Change from baseline at Month 12
6.9 Score on a scale
Standard Deviation 12.65
Mean Change in Patient-reported Outcomes in NEI-VFQ-25 Composite and Subscale Scores at Month 12 and Month 24 Compared to Baseline
Change from baseline at Month 24
6.6 Score on a scale
Standard Deviation 14.03

Adverse Events

Ranibizumab 0.5mg

Serious events: 64 serious events
Other events: 244 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ranibizumab 0.5mg
n=357 participants at risk
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Blood and lymphatic system disorders
Anaemia
0.28%
1/357
Cardiac disorders
Angina pectoris
0.28%
1/357
Cardiac disorders
Atrial fibrillation
0.84%
3/357
Cardiac disorders
Cardiac failure
0.84%
3/357
Cardiac disorders
Cardiac failure acute
0.28%
1/357
Cardiac disorders
Cardiac failure congestive
0.84%
3/357
Cardiac disorders
Cardiopulmonary failure
0.28%
1/357
Cardiac disorders
Left ventricular dysfunction
0.28%
1/357
Cardiac disorders
Myocardial infarction
0.84%
3/357
Cardiac disorders
Right ventricular failure
0.28%
1/357
Cardiac disorders
Sinus tachycardia
0.28%
1/357
Ear and labyrinth disorders
Vertigo
0.28%
1/357
Eye disorders
Cataract (Fellow untreated eye)
0.28%
1/357
Eye disorders
Cataract (Study eye)
0.28%
1/357
Eye disorders
Glaucoma (Fellow untreated eye)
0.28%
1/357
Eye disorders
Glaucoma (Study eye)
0.56%
2/357
Eye disorders
Hyphaema (Fellow untreated eye)
0.28%
1/357
Eye disorders
Hyphaema (Study eye)
0.28%
1/357
Eye disorders
Myopia (Study eye)
0.28%
1/357
Eye disorders
Retinal haemorrhage (Study eye)
0.28%
1/357
Eye disorders
Retinal ischaemia (Study eye)
0.56%
2/357
Eye disorders
Retinal vascular thrombosis (Study eye)
0.28%
1/357
Eye disorders
Visual acuity reduced (Study eye)
0.56%
2/357
Eye disorders
Vitreous haemorrhage (Fellow untreated eye)
0.28%
1/357
Eye disorders
Vitreous haemorrhage (Study eye)
0.28%
1/357
Gastrointestinal disorders
Abdominal adhesions
0.28%
1/357
Gastrointestinal disorders
Abdominal pain upper
0.28%
1/357
Gastrointestinal disorders
Colitis
0.28%
1/357
Gastrointestinal disorders
Diverticular perforation
0.28%
1/357
Gastrointestinal disorders
Duodenal ulcer
0.28%
1/357
Gastrointestinal disorders
Gastrointestinal polyp haemorrhage
0.28%
1/357
Gastrointestinal disorders
Inguinal hernia
0.28%
1/357
Gastrointestinal disorders
Intestinal obstruction
0.28%
1/357
Gastrointestinal disorders
Large intestine polyp
0.28%
1/357
Gastrointestinal disorders
Pancreatitis
0.28%
1/357
Gastrointestinal disorders
Pancreatitis acute
0.56%
2/357
General disorders
Chest pain
0.28%
1/357
General disorders
Death
0.28%
1/357
General disorders
Non-cardiac chest pain
0.28%
1/357
Hepatobiliary disorders
Cholecystitis
0.28%
1/357
Hepatobiliary disorders
Cholecystitis acute
0.28%
1/357
Hepatobiliary disorders
Cholelithiasis
0.28%
1/357
Infections and infestations
Appendicitis
0.28%
1/357
Infections and infestations
Febrile infection
0.28%
1/357
Infections and infestations
Gangrene
0.28%
1/357
Infections and infestations
Lower respiratory tract infection
0.84%
3/357
Infections and infestations
Ophthalmic herpes zoster (Fellow untreated eye)
0.28%
1/357
Infections and infestations
Pneumonia
0.84%
3/357
Infections and infestations
Pneumonia viral
0.28%
1/357
Infections and infestations
Sepsis
0.28%
1/357
Infections and infestations
Septic shock
0.28%
1/357
Infections and infestations
Urosepsis
0.28%
1/357
Injury, poisoning and procedural complications
Femoral neck fracture
0.56%
2/357
Injury, poisoning and procedural complications
Hip fracture
0.28%
1/357
Injury, poisoning and procedural complications
Humerus fracture
0.28%
1/357
Injury, poisoning and procedural complications
Laceration
0.28%
1/357
Injury, poisoning and procedural complications
Limb traumatic amputation
0.28%
1/357
Injury, poisoning and procedural complications
Rib fracture
0.28%
1/357
Injury, poisoning and procedural complications
Scapula fracture
0.28%
1/357
Injury, poisoning and procedural complications
Spinal fracture
0.28%
1/357
Investigations
Intraocular pressure increased (Study eye)
0.28%
1/357
Investigations
Visual acuity tests abnormal (Study eye)
0.28%
1/357
Metabolism and nutrition disorders
Hypoglycaemia
0.28%
1/357
Metabolism and nutrition disorders
Hypokalaemia
0.28%
1/357
Metabolism and nutrition disorders
Hyponatraemia
0.28%
1/357
Musculoskeletal and connective tissue disorders
Gouty arthritis
0.28%
1/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
0.28%
1/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
0.56%
2/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
0.28%
1/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.56%
2/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cholangiocarcinoma
0.28%
1/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
0.28%
1/357
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
0.28%
1/357
Nervous system disorders
Brain hypoxia
0.28%
1/357
Nervous system disorders
Cerebrovascular accident
0.56%
2/357
Psychiatric disorders
Anxiety
0.56%
2/357
Psychiatric disorders
Depression
0.28%
1/357
Psychiatric disorders
Major depression
0.28%
1/357
Renal and urinary disorders
Renal failure
0.28%
1/357
Renal and urinary disorders
Renal failure acute
0.56%
2/357
Renal and urinary disorders
Renal mass
0.28%
1/357
Reproductive system and breast disorders
Haemorrhagic ovarian cyst
0.28%
1/357
Respiratory, thoracic and mediastinal disorders
Asthma
0.28%
1/357
Respiratory, thoracic and mediastinal disorders
Pleural effusion
0.56%
2/357
Vascular disorders
Aneurysm ruptured
0.28%
1/357
Vascular disorders
Angiopathy
0.28%
1/357
Vascular disorders
Diabetic vascular disorder
0.28%
1/357
Vascular disorders
Hypertension
0.56%
2/357
Vascular disorders
Hypertensive crisis
0.28%
1/357
Vascular disorders
Hypotension
0.28%
1/357
Vascular disorders
Peripheral arterial occlusive disease
0.28%
1/357
Vascular disorders
Peripheral artery aneurysm
0.28%
1/357

Other adverse events

Other adverse events
Measure
Ranibizumab 0.5mg
n=357 participants at risk
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Eye disorders
Blepharitis (Study eye)
3.4%
12/357
Eye disorders
Cataract (Fellow untreated eye)
3.1%
11/357
Eye disorders
Cataract (Study eye)
4.2%
15/357
Eye disorders
Conjunctival haemorrhage (Study eye)
6.7%
24/357
Eye disorders
Dry eye (Fellow untreated eye)
5.3%
19/357
Eye disorders
Dry eye (Study eye)
6.2%
22/357
Eye disorders
Eye pain (Study eye)
7.0%
25/357
Eye disorders
Eyelid oedema (Study eye)
2.5%
9/357
Eye disorders
Glaucoma (Fellow untreated eye)
2.8%
10/357
Eye disorders
Glaucoma (Study eye)
3.1%
11/357
Eye disorders
Macular fibrosis (Study eye)
4.2%
15/357
Eye disorders
Macular oedema (Study eye)
5.3%
19/357
Eye disorders
Ocular discomfort (Study eye)
2.8%
10/357
Eye disorders
Ocular hyperaemia (Study eye)
2.5%
9/357
Eye disorders
Ocular hypertension (Fellow untreated eye)
2.2%
8/357
Eye disorders
Ocular hypertension (Study eye)
7.3%
26/357
Eye disorders
Vision blurred (Study eye)
5.0%
18/357
Eye disorders
Visual acuity reduced (Study eye)
5.9%
21/357
Eye disorders
Vitreous detachment (Study eye)
3.4%
12/357
Eye disorders
Vitreous floaters (Study eye)
5.3%
19/357
Gastrointestinal disorders
Diarrhoea
3.1%
11/357
General disorders
Injection site pain (Study eye)
3.1%
11/357
Infections and infestations
Bronchitis
4.2%
15/357
Infections and infestations
Conjunctivitis (Fellow untreated eye)
2.2%
8/357
Infections and infestations
Conjunctivitis (Study eye)
2.8%
10/357
Infections and infestations
Influenza
4.8%
17/357
Infections and infestations
Lower respiratory tract infection
2.2%
8/357
Infections and infestations
Nasopharyngitis
10.9%
39/357
Infections and infestations
Pneumonia
2.2%
8/357
Infections and infestations
Sinusitis
2.5%
9/357
Infections and infestations
Tooth infection
2.5%
9/357
Infections and infestations
Upper respiratory tract infection
3.4%
12/357
Infections and infestations
Urinary tract infection
2.5%
9/357
Injury, poisoning and procedural complications
Fall
4.2%
15/357
Investigations
Intraocular pressure increased (Fellow untreated eye)
3.1%
11/357
Investigations
Intraocular pressure increased (Study eye)
12.0%
43/357
Musculoskeletal and connective tissue disorders
Arthralgia
2.5%
9/357
Musculoskeletal and connective tissue disorders
Back pain
3.6%
13/357
Nervous system disorders
Dizziness
3.1%
11/357
Nervous system disorders
Headache
5.9%
21/357
Respiratory, thoracic and mediastinal disorders
Cough
3.6%
13/357
Vascular disorders
Hypertension
11.2%
40/357

Additional Information

Study Director

Novartis

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