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Trial record 35 of 81 for:    CRVO - Central Retinal Vein Occlusion

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

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: NCT01535261
Recruitment Status : Completed
First Posted : February 17, 2012
Results First Posted : June 3, 2016
Last Update Posted : October 27, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Macular Edema
Central Retinal Vein Occlusion
Intervention Drug: Ranibizumab 0.5 mg/0.05 ml
Enrollment 357
Recruitment Details  
Pre-assignment Details No data were excluded from the Full Analysis Set (FAS )analyses because of protocol deviations.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Period Title: Overall Study
Started 357
Completed 307
Not Completed 50
Reason Not Completed
Physician Decision             8
Protocol Violation             3
Death             5
Lost to Follow-up             8
Withdrawal by Subject             14
Adverse Event             12
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Baseline Participants 357
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 357 participants
65.5  (12.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 357 participants
Female
128
  35.9%
Male
229
  64.1%
1.Primary Outcome
Title Mean Change in Best Corrected Visual Acuity (BCVA) at Month 12 Compared to Baseline
Hide Description 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
Time Frame Baseline to month 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 356
Mean (Standard Deviation)
Unit of Measure: Letters
12.3  (16.72)
2.Secondary Outcome
Title Mean Change in Best Corrected Visual Acuity (BCVA) at Month 24 Compared to Baseline
Hide Description 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
Time Frame Baseline to Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 356
Mean (Standard Deviation)
Unit of Measure: Letters
12.1  (18.60)
3.Secondary Outcome
Title Mean Average Change in Best Corrected Visual Acuity (BCVA From Baseline Month 12 and Month 24
Hide Description 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.
Time Frame Baseline and Month 1 to 12 or Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 356
Mean (Standard Deviation)
Unit of Measure: letters
Month 12 11.8  (12.44)
Month 24 12.1  (14.20)
4.Secondary Outcome
Title Mean Average Change in BCVA From First Treatment Interruption (Due to BCVA Stabilization) to Month 12 and Month 24
Hide Description 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
Time Frame Month 12 and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 356
Mean (Standard Deviation)
Unit of Measure: Letters
Month 12 (n=310) -2.7  (8.04)
Month 24 (n=331) -2.5  (8.95)
5.Secondary Outcome
Title 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
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 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
Time Frame Month 12 and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 356
Measure Type: Number
Unit of Measure: Letters
BCVA improvement of >= 1 (Month 12) 296
BCVA improvement of >= 5 (Month 12) 275
BCVA improvement of >= 10 (Month 12) 227
BCVA improvement of >= 15 (Month 12) 175
BCVA improvement of >= 30 (Month 12) 32
BCVA improvement of >= 1 (Month 24) 290
BCVA improvement of >= 5 (Month 24) 265
BCVA improvement of >= 10 (Month 24) 224
BCVA improvement of >= 15 (Month 24) 175
BCVA improvement of >= 30 (Month 24) 44
6.Secondary Outcome
Title Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 and Month 24
Hide Description 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.
Time Frame Month 12 and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 356
Measure Type: Number
Unit of Measure: Letters
Month 12 169
Month 24 161
7.Secondary Outcome
Title Mean Change in Central Reading Center (CRC)-Assessed Central Subfield Thickness (CSFT) From Month 12 and Month 24 Compared to Baseline
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 12 and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 347
Mean (Standard Deviation)
Unit of Measure: Microns
Change from Baseline at Month 12 -335.7  (285.02)
Change from Baseline at Month 24 -349.1  (275.35)
8.Secondary Outcome
Title Mean Change in Patient-reported Outcomes in NEI-VFQ-25 Composite and Subscale Scores at Month 12 and Month 24 Compared to Baseline
Hide Description 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.
Time Frame Month 12 and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Ranibizumab Arm
Hide Arm/Group Description:
Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Number of Participants Analyzed 350
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Change from baseline at Month 12 6.9  (12.65)
Change from baseline at Month 24 6.6  (14.03)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ranibizumab 0.5mg
Hide Arm/Group Description Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
All-Cause Mortality
Ranibizumab 0.5mg
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ranibizumab 0.5mg
Affected / at Risk (%)
Total   64/357 (17.93%) 
Blood and lymphatic system disorders   
Anaemia  1  1/357 (0.28%) 
Cardiac disorders   
Angina pectoris  1  1/357 (0.28%) 
Atrial fibrillation  1  3/357 (0.84%) 
Cardiac failure  1  3/357 (0.84%) 
Cardiac failure acute  1  1/357 (0.28%) 
Cardiac failure congestive  1  3/357 (0.84%) 
Cardiopulmonary failure  1  1/357 (0.28%) 
Left ventricular dysfunction  1  1/357 (0.28%) 
Myocardial infarction  1  3/357 (0.84%) 
Right ventricular failure  1  1/357 (0.28%) 
Sinus tachycardia  1  1/357 (0.28%) 
Ear and labyrinth disorders   
Vertigo  1  1/357 (0.28%) 
Eye disorders   
Cataract (Fellow untreated eye)  1  1/357 (0.28%) 
Cataract (Study eye)  1  1/357 (0.28%) 
Glaucoma (Fellow untreated eye)  1  1/357 (0.28%) 
Glaucoma (Study eye)  1  2/357 (0.56%) 
Hyphaema (Fellow untreated eye)  1  1/357 (0.28%) 
Hyphaema (Study eye)  1  1/357 (0.28%) 
Myopia (Study eye)  1  1/357 (0.28%) 
Retinal haemorrhage (Study eye)  1  1/357 (0.28%) 
Retinal ischaemia (Study eye)  1  2/357 (0.56%) 
Retinal vascular thrombosis (Study eye)  1  1/357 (0.28%) 
Visual acuity reduced (Study eye)  1  2/357 (0.56%) 
Vitreous haemorrhage (Fellow untreated eye)  1  1/357 (0.28%) 
Vitreous haemorrhage (Study eye)  1  1/357 (0.28%) 
Gastrointestinal disorders   
Abdominal adhesions  1  1/357 (0.28%) 
Abdominal pain upper  1  1/357 (0.28%) 
Colitis  1  1/357 (0.28%) 
Diverticular perforation  1  1/357 (0.28%) 
Duodenal ulcer  1  1/357 (0.28%) 
Gastrointestinal polyp haemorrhage  1  1/357 (0.28%) 
Inguinal hernia  1  1/357 (0.28%) 
Intestinal obstruction  1  1/357 (0.28%) 
Large intestine polyp  1  1/357 (0.28%) 
Pancreatitis  1  1/357 (0.28%) 
Pancreatitis acute  1  2/357 (0.56%) 
General disorders   
Chest pain  1  1/357 (0.28%) 
Death  1  1/357 (0.28%) 
Non-cardiac chest pain  1  1/357 (0.28%) 
Hepatobiliary disorders   
Cholecystitis  1  1/357 (0.28%) 
Cholecystitis acute  1  1/357 (0.28%) 
Cholelithiasis  1  1/357 (0.28%) 
Infections and infestations   
Appendicitis  1  1/357 (0.28%) 
Febrile infection  1  1/357 (0.28%) 
Gangrene  1  1/357 (0.28%) 
Lower respiratory tract infection  1  3/357 (0.84%) 
Ophthalmic herpes zoster (Fellow untreated eye)  1  1/357 (0.28%) 
Pneumonia  1  3/357 (0.84%) 
Pneumonia viral  1  1/357 (0.28%) 
Sepsis  1  1/357 (0.28%) 
Septic shock  1  1/357 (0.28%) 
Urosepsis  1  1/357 (0.28%) 
Injury, poisoning and procedural complications   
Femoral neck fracture  1  2/357 (0.56%) 
Hip fracture  1  1/357 (0.28%) 
Humerus fracture  1  1/357 (0.28%) 
Laceration  1  1/357 (0.28%) 
Limb traumatic amputation  1  1/357 (0.28%) 
Rib fracture  1  1/357 (0.28%) 
Scapula fracture  1  1/357 (0.28%) 
Spinal fracture  1  1/357 (0.28%) 
Investigations   
Intraocular pressure increased (Study eye)  1  1/357 (0.28%) 
Visual acuity tests abnormal (Study eye)  1  1/357 (0.28%) 
Metabolism and nutrition disorders   
Hypoglycaemia  1  1/357 (0.28%) 
Hypokalaemia  1  1/357 (0.28%) 
Hyponatraemia  1  1/357 (0.28%) 
Musculoskeletal and connective tissue disorders   
Gouty arthritis  1  1/357 (0.28%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Basal cell carcinoma  1  1/357 (0.28%) 
Bladder cancer  1  2/357 (0.56%) 
Bladder transitional cell carcinoma  1  1/357 (0.28%) 
Breast cancer  1  2/357 (0.56%) 
Cholangiocarcinoma  1  1/357 (0.28%) 
Prostate cancer  1  1/357 (0.28%) 
Renal cell carcinoma  1  1/357 (0.28%) 
Nervous system disorders   
Brain hypoxia  1  1/357 (0.28%) 
Cerebrovascular accident  1  2/357 (0.56%) 
Psychiatric disorders   
Anxiety  1  2/357 (0.56%) 
Depression  1  1/357 (0.28%) 
Major depression  1  1/357 (0.28%) 
Renal and urinary disorders   
Renal failure  1  1/357 (0.28%) 
Renal failure acute  1  2/357 (0.56%) 
Renal mass  1  1/357 (0.28%) 
Reproductive system and breast disorders   
Haemorrhagic ovarian cyst  1  1/357 (0.28%) 
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/357 (0.28%) 
Pleural effusion  1  2/357 (0.56%) 
Vascular disorders   
Aneurysm ruptured  1  1/357 (0.28%) 
Angiopathy  1  1/357 (0.28%) 
Diabetic vascular disorder  1  1/357 (0.28%) 
Hypertension  1  2/357 (0.56%) 
Hypertensive crisis  1  1/357 (0.28%) 
Hypotension  1  1/357 (0.28%) 
Peripheral arterial occlusive disease  1  1/357 (0.28%) 
Peripheral artery aneurysm  1  1/357 (0.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Ranibizumab 0.5mg
Affected / at Risk (%)
Total   244/357 (68.35%) 
Eye disorders   
Blepharitis (Study eye)  1  12/357 (3.36%) 
Cataract (Fellow untreated eye)  1  11/357 (3.08%) 
Cataract (Study eye)  1  15/357 (4.20%) 
Conjunctival haemorrhage (Study eye)  1  24/357 (6.72%) 
Dry eye (Fellow untreated eye)  1  19/357 (5.32%) 
Dry eye (Study eye)  1  22/357 (6.16%) 
Eye pain (Study eye)  1  25/357 (7.00%) 
Eyelid oedema (Study eye)  1  9/357 (2.52%) 
Glaucoma (Fellow untreated eye)  1  10/357 (2.80%) 
Glaucoma (Study eye)  1  11/357 (3.08%) 
Macular fibrosis (Study eye)  1  15/357 (4.20%) 
Macular oedema (Study eye)  1  19/357 (5.32%) 
Ocular discomfort (Study eye)  1  10/357 (2.80%) 
Ocular hyperaemia (Study eye)  1  9/357 (2.52%) 
Ocular hypertension (Fellow untreated eye)  1  8/357 (2.24%) 
Ocular hypertension (Study eye)  1  26/357 (7.28%) 
Vision blurred (Study eye)  1  18/357 (5.04%) 
Visual acuity reduced (Study eye)  1  21/357 (5.88%) 
Vitreous detachment (Study eye)  1  12/357 (3.36%) 
Vitreous floaters (Study eye)  1  19/357 (5.32%) 
Gastrointestinal disorders   
Diarrhoea  1  11/357 (3.08%) 
General disorders   
Injection site pain (Study eye)  1  11/357 (3.08%) 
Infections and infestations   
Bronchitis  1  15/357 (4.20%) 
Conjunctivitis (Fellow untreated eye)  1  8/357 (2.24%) 
Conjunctivitis (Study eye)  1  10/357 (2.80%) 
Influenza  1  17/357 (4.76%) 
Lower respiratory tract infection  1  8/357 (2.24%) 
Nasopharyngitis  1  39/357 (10.92%) 
Pneumonia  1  8/357 (2.24%) 
Sinusitis  1  9/357 (2.52%) 
Tooth infection  1  9/357 (2.52%) 
Upper respiratory tract infection  1  12/357 (3.36%) 
Urinary tract infection  1  9/357 (2.52%) 
Injury, poisoning and procedural complications   
Fall  1  15/357 (4.20%) 
Investigations   
Intraocular pressure increased (Fellow untreated eye)  1  11/357 (3.08%) 
Intraocular pressure increased (Study eye)  1  43/357 (12.04%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  9/357 (2.52%) 
Back pain  1  13/357 (3.64%) 
Nervous system disorders   
Dizziness  1  11/357 (3.08%) 
Headache  1  21/357 (5.88%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  13/357 (3.64%) 
Vascular disorders   
Hypertension  1  40/357 (11.20%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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
Name/Title: Study Director
Organization: Novartis
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01535261     History of Changes
Other Study ID Numbers: CRFB002E2401
2011-002350-31 ( EudraCT Number )
First Submitted: February 14, 2012
First Posted: February 17, 2012
Results First Submitted: March 16, 2016
Results First Posted: June 3, 2016
Last Update Posted: October 27, 2016