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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01535261

Collaborator

(none)

357

Enrollment

Locations

Arm

36.9

Duration (Months)

4.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The present study provided additional efficacy and safety data for 0.5-mg ranibizumab using as needed (PRN) dosing over 24 months in patients with visual impairment due to macular edema secondary to Central Retinal Vein Occlusion (CRVO). Spectral domain high-definition optical coherence tomography (OCT) images was analyzed to gain insights into predictive factors for disease progression and the possibility of reduced monitoring was assessed in Year 2. The results of this open-label study provided long-term safety and efficacy data to further guide recommendations on the use of ranibizumab in this indication.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema Central Retinal Vein Occlusion	Drug: Ranibizumab 0.5 mg/0.05 ml	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

357 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A 24-month, Phase IIIb, Open-label, Single Arm, Multicenter Study Assessing the Efficacy and Safety of an Individualized, Stabilization-criteria-driven PRN Dosing Regimen With 0.5-mg Ranibizumab Intravitreal Injections Applied as Monotherapy in Patients With Visual Impairment Due to Macular Edema Secondary to Central Retinal

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab arm Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN	Drug: Ranibizumab 0.5 mg/0.05 ml Patients will receive the first dose at Baseline, as an intravitreal injection with a standard dose of 0.5 mg/0.05 ml. Patients will receive at least 3 study treatments at monthly intervals (Day 1, Month 1 and Month 2). The last mandatory dose during treatment initiation will be administered approximately 60 days after the first study treatment. If there is no improvement in VA over the course of the first 3 injections, continued treatment is not recommended and the patient may receive alternative treatment at the investigator's discretion.

Arm

Intervention/Treatment

Experimental: Ranibizumab arm

Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN

Drug: Ranibizumab 0.5 mg/0.05 ml

Patients will receive the first dose at Baseline, as an intravitreal injection with a standard dose of 0.5 mg/0.05 ml. Patients will receive at least 3 study treatments at monthly intervals (Day 1, Month 1 and Month 2). The last mandatory dose during treatment initiation will be administered approximately 60 days after the first study treatment. If there is no improvement in VA over the course of the first 3 injections, continued treatment is not recommended and the patient may receive alternative treatment at the investigator's discretion.

Outcome Measures

Primary Outcome Measures

Mean Change in Best Corrected Visual Acuity (BCVA) at Month 12 Compared to Baseline [Baseline to month 12]
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

Secondary Outcome Measures

Mean Change in Best Corrected Visual Acuity (BCVA) at Month 24 Compared to Baseline [Baseline to Month 24]
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
Mean Average Change in Best Corrected Visual Acuity (BCVA From Baseline Month 12 and Month 24 [Baseline and Month 1 to 12 or Month 24]
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.
Mean Average Change in BCVA From First Treatment Interruption (Due to BCVA Stabilization) to Month 12 and Month 24 [Month 12 and Month 24]
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
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 [Month 12 and Month 24]
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
Number of Patients With a BCVA Value of ≥ 73 Letters (Approximate 20/40 Snellen Chart Equivalent) at Month 12 and Month 24 [Month 12 and Month 24]
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.
Mean Change in Central Reading Center (CRC)-Assessed Central Subfield Thickness (CSFT) From Month 12 and Month 24 Compared to Baseline [Baseline, Month 12 and Month 24]
Retinal thickness was measured using Optical Coherence Tomography (OCT). The images were reviewed by a central reading center to ensure a standardized evaluation
Mean Change in Patient-reported Outcomes in NEI-VFQ-25 Composite and Subscale Scores at Month 12 and Month 24 Compared to Baseline [Month 12 and Month 24]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female patients ≥ 18 years of age
Diagnosis of visual impairment exclusively due to ME secondary to CRVO
BCVA score at Screening and Baseline between 73 and 19 letters Early Treatment Diabetic Retinopathy Study (ETDRS), inclusively (approximate Snellen chart equivalent of 20/40 and 20/400)

Exclusion Criteria:

Uncontrolled blood pressure defined as systolic value of > 160 mm Hg or diastolic value of > 100 mm Hg at Screening or Baseline.
Any active periocular or ocular infection or inflammation at Screening or Baseline in either eye
Uncontrolled glaucoma at Screening or Baseline or diagnosed within 6 months before Baseline in either eye
Use of any systemic antivascular endothelial growth factor (anti-VEGF) drugs within 6 months before Baseline (eg, sorafenib [Nexavar®], sunitinib [Sutent®], bevacizumab [Avastin®])

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Parramatta	New South Wales	Australia	2150
2	Novartis Investigative Site	Sydney	New South Wales	Australia	2000
3	Novartis Investigative Site	Melbourne	Victoria	Australia	3002
4	Novartis Investigative Site	Nedlands	Western Australia	Australia	6009
5	Novartis Investigative Site	Linz		Austria	4021
6	Novartis Investigative Site	Wien		Austria	1090
7	Novartis Investigative Site	Calgary	Alberta	Canada	T2H0C8
8	Novartis Investigative Site	Vancouver	British Columbia	Canada	V5Z 1M9
9	Novartis Investigative Site	Victoria	British Columbia	Canada	V8V 4X3
10	Novartis Investigative Site	London	Ontario	Canada	N6A 4G5
11	Novartis Investigative Site	Boisbriand	Quebec	Canada	J7H 1S6
12	Novartis Investigative Site	Montreal	Quebec	Canada	H1T 2M4
13	Novartis Investigative Site	Olomouc		Czech Republic	775 20
14	Novartis Investigative Site	Praha 10		Czech Republic	100 34
15	Novartis Investigative Site	Glostrup		Denmark	DK-2600
16	Novartis Investigative Site	Athens	GR	Greece	124 62
17	Novartis Investigative Site	Heraklion Crete	GR	Greece	711 10
18	Novartis Investigative Site	Larissa	GR	Greece	411 10
19	Novartis Investigative Site	Thessaloniki	GR	Greece	546 29
20	Novartis Investigative Site	Patras		Greece	26504
21	Novartis Investigative Site	Thessaloniki		Greece	GR 54636
22	Novartis Investigative Site	Budapest		Hungary	1133
23	Novartis Investigative Site	Budapest		Hungary	H-1083
24	Novartis Investigative Site	Debrecen		Hungary	4032
25	Novartis Investigative Site	Dublin 7		Ireland
26	Novartis Investigative Site	Dublin		Ireland
27	Novartis Investigative Site	Bologna	BO	Italy	40138
28	Novartis Investigative Site	Firenze	FI	Italy	50134
29	Novartis Investigative Site	Milano	MI	Italy	20100
30	Novartis Investigative Site	Milano	MI	Italy	20132
31	Novartis Investigative Site	Roma	RM	Italy	00144
32	Novartis Investigative Site	Torino	TO	Italy	10122
33	Novartis Investigative Site	Udine		Italy	33100
34	Novartis Investigative Site	Amsterdam		Netherlands	1081
35	Novartis Investigative Site	Leiden 2333 ZA		Netherlands	2333
36	Novartis Investigative Site	Nijmegen		Netherlands	6525 GA
37	Novartis Investigative Site	Rotterdam		Netherlands	3011 BH
38	Novartis Investigative Site	Tilburg		Netherlands	5022 GC
39	Novartis Investigative Site	Bielsko-Biala		Poland	43-300
40	Novartis Investigative Site	Gdansk		Poland	80-809
41	Novartis Investigative Site	Kraków		Poland	31-501
42	Novartis Investigative Site	Lublin		Poland	20-079
43	Novartis Investigative Site	Warszawa		Poland	02-005
44	Novartis Investigative Site	Wroclaw		Poland	50-556
45	Novartis Investigative Site	Coimbra		Portugal	3000-354
46	Novartis Investigative Site	Coimbra		Portugal	3030-163
47	Novartis Investigative Site	Lisboa		Portugal	1050-085
48	Novartis Investigative Site	Lisboa		Portugal	1349-019
49	Novartis Investigative Site	Porto		Portugal	4099-001
50	Novartis Investigative Site	Porto		Portugal	4200-319
51	Novartis Investigative Site	Zilina	Slovak Republic	Slovakia	010 01
52	Novartis Investigative Site	Banska Bystrica		Slovakia	975 17
53	Novartis Investigative Site	Bratislava		Slovakia	826 06
54	Novartis Investigative Site	Valladolid	Castilla y Leon	Spain	47011
55	Novartis Investigative Site	Barcelona	Cataluña	Spain	08022
56	Novartis Investigative Site	Barcelona	Cataluña	Spain
57	Novartis Investigative Site	L´Hospitalet de Llobregat	Cataluña	Spain	08907
58	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03016
59	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46014
60	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46015
61	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
62	Novartis Investigative Site	Bilbao	Pais Vasco	Spain	48006
63	Novartis Investigative Site	Örebro		Sweden	701 85
64	Novartis Investigative Site	Bern		Switzerland	3012
65	Novartis Investigative Site	Lausanne		Switzerland	1007
66	Novartis Investigative Site	Zuerich		Switzerland	8063
67	Novartis Investigative Site	Ankara		Turkey	06100
68	Novartis Investigative Site	Frimley	Surrey	United Kingdom	GU16 7UJ
69	Novartis Investigative Site	Belfast		United Kingdom	BT12 6BA
70	Novartis Investigative Site	Birmingham		United Kingdom	B9 5SS
71	Novartis Investigative Site	Bristol		United Kingdom	BS1 2LX
72	Novartis Investigative Site	Hull		United Kingdom	HU3 2JZ
73	Novartis Investigative Site	Liverpool		United Kingdom	L69 3GA
74	Novartis Investigative Site	London		United Kingdom	EC1V 2PD
75	Novartis Investigative Site	London		United Kingdom	NW1 5QH
76	Novartis Investigative Site	Newcastle upon Tyne		United Kingdom	NE1 4LP
77	Novartis Investigative Site	Plymouth		United Kingdom	PL4 6PL
78	Novartis Investigative Site	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01535261

Other Study ID Numbers:

CRFB002E2401
2011-002350-31

First Posted:

Feb 17, 2012

Last Update Posted:

Oct 27, 2016

Last Verified:

Sep 1, 2016

Keywords provided by Novartis Pharmaceuticals

Ophthalmology

Ranibizumab

Central Retinal Vein Occlusion

Additional relevant MeSH terms:

Vision Disorders

Vision, Low

Macular Edema

Retinal Vein Occlusion

Edema

Ranibizumab

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail	No data were excluded from the Full Analysis Set (FAS )analyses because of protocol deviations.

Arm/Group Title	Ranibizumab Arm
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

Baseline Characteristics

Arm/Group Title	Ranibizumab Arm
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Overall Participants	357
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.5 (12.68)
Sex: Female, Male (Count of Participants)
Female	128 35.9%
Male	229 64.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA) at Month 12 Compared to Baseline
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	356
Mean (Standard Deviation) [Letters]	12.3 (16.72)

2. Secondary Outcome

Title	Mean Change in Best Corrected Visual Acuity (BCVA) at Month 24 Compared to Baseline
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	356
Mean (Standard Deviation) [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
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	356
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
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	356
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
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	356
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
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	356
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
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	347
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
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

Outcome Measure Data

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
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
Measure Participants	350
Change from baseline at Month 12	6.9 (12.65)
Change from baseline at Month 24	6.6 (14.03)

Adverse Events

	Ranibizumab 0.5mg
Time Frame
Adverse Event Reporting Description

Arm/Group Title	Ranibizumab 0.5mg
Arm/Group Description	Intravitreal injection with standard dose of 0.5 mg/0.05mL PRN
All Cause Mortality
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ranibizumab 0.5mg
	Affected / at Risk (%)	# Events
Total	64/357 (17.9%)
Blood and lymphatic system disorders
Anaemia	1/357 (0.3%)
Cardiac disorders
Angina pectoris	1/357 (0.3%)
Atrial fibrillation	3/357 (0.8%)
Cardiac failure	3/357 (0.8%)
Cardiac failure acute	1/357 (0.3%)
Cardiac failure congestive	3/357 (0.8%)
Cardiopulmonary failure	1/357 (0.3%)
Left ventricular dysfunction	1/357 (0.3%)
Myocardial infarction	3/357 (0.8%)
Right ventricular failure	1/357 (0.3%)
Sinus tachycardia	1/357 (0.3%)
Ear and labyrinth disorders
Vertigo	1/357 (0.3%)
Eye disorders
Cataract (Fellow untreated eye)	1/357 (0.3%)
Cataract (Study eye)	1/357 (0.3%)
Glaucoma (Fellow untreated eye)	1/357 (0.3%)
Glaucoma (Study eye)	2/357 (0.6%)
Hyphaema (Fellow untreated eye)	1/357 (0.3%)
Hyphaema (Study eye)	1/357 (0.3%)
Myopia (Study eye)	1/357 (0.3%)
Retinal haemorrhage (Study eye)	1/357 (0.3%)
Retinal ischaemia (Study eye)	2/357 (0.6%)
Retinal vascular thrombosis (Study eye)	1/357 (0.3%)
Visual acuity reduced (Study eye)	2/357 (0.6%)
Vitreous haemorrhage (Fellow untreated eye)	1/357 (0.3%)
Vitreous haemorrhage (Study eye)	1/357 (0.3%)
Gastrointestinal disorders
Abdominal adhesions	1/357 (0.3%)
Abdominal pain upper	1/357 (0.3%)
Colitis	1/357 (0.3%)
Diverticular perforation	1/357 (0.3%)
Duodenal ulcer	1/357 (0.3%)
Gastrointestinal polyp haemorrhage	1/357 (0.3%)
Inguinal hernia	1/357 (0.3%)
Intestinal obstruction	1/357 (0.3%)
Large intestine polyp	1/357 (0.3%)
Pancreatitis	1/357 (0.3%)
Pancreatitis acute	2/357 (0.6%)
General disorders
Chest pain	1/357 (0.3%)
Death	1/357 (0.3%)
Non-cardiac chest pain	1/357 (0.3%)
Hepatobiliary disorders
Cholecystitis	1/357 (0.3%)
Cholecystitis acute	1/357 (0.3%)
Cholelithiasis	1/357 (0.3%)
Infections and infestations
Appendicitis	1/357 (0.3%)
Febrile infection	1/357 (0.3%)
Gangrene	1/357 (0.3%)
Lower respiratory tract infection	3/357 (0.8%)
Ophthalmic herpes zoster (Fellow untreated eye)	1/357 (0.3%)
Pneumonia	3/357 (0.8%)
Pneumonia viral	1/357 (0.3%)
Sepsis	1/357 (0.3%)
Septic shock	1/357 (0.3%)
Urosepsis	1/357 (0.3%)
Injury, poisoning and procedural complications
Femoral neck fracture	2/357 (0.6%)
Hip fracture	1/357 (0.3%)
Humerus fracture	1/357 (0.3%)
Laceration	1/357 (0.3%)
Limb traumatic amputation	1/357 (0.3%)
Rib fracture	1/357 (0.3%)
Scapula fracture	1/357 (0.3%)
Spinal fracture	1/357 (0.3%)
Investigations
Intraocular pressure increased (Study eye)	1/357 (0.3%)
Visual acuity tests abnormal (Study eye)	1/357 (0.3%)
Metabolism and nutrition disorders
Hypoglycaemia	1/357 (0.3%)
Hypokalaemia	1/357 (0.3%)
Hyponatraemia	1/357 (0.3%)
Musculoskeletal and connective tissue disorders
Gouty arthritis	1/357 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/357 (0.3%)
Bladder cancer	2/357 (0.6%)
Bladder transitional cell carcinoma	1/357 (0.3%)
Breast cancer	2/357 (0.6%)
Cholangiocarcinoma	1/357 (0.3%)
Prostate cancer	1/357 (0.3%)
Renal cell carcinoma	1/357 (0.3%)
Nervous system disorders
Brain hypoxia	1/357 (0.3%)
Cerebrovascular accident	2/357 (0.6%)
Psychiatric disorders
Anxiety	2/357 (0.6%)
Depression	1/357 (0.3%)
Major depression	1/357 (0.3%)
Renal and urinary disorders
Renal failure	1/357 (0.3%)
Renal failure acute	2/357 (0.6%)
Renal mass	1/357 (0.3%)
Reproductive system and breast disorders
Haemorrhagic ovarian cyst	1/357 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/357 (0.3%)
Pleural effusion	2/357 (0.6%)
Vascular disorders
Aneurysm ruptured	1/357 (0.3%)
Angiopathy	1/357 (0.3%)
Diabetic vascular disorder	1/357 (0.3%)
Hypertension	2/357 (0.6%)
Hypertensive crisis	1/357 (0.3%)
Hypotension	1/357 (0.3%)
Peripheral arterial occlusive disease	1/357 (0.3%)
Peripheral artery aneurysm	1/357 (0.3%)
Other (Not Including Serious) Adverse Events
	Ranibizumab 0.5mg
	Affected / at Risk (%)	# Events
Total	244/357 (68.3%)
Eye disorders
Blepharitis (Study eye)	12/357 (3.4%)
Cataract (Fellow untreated eye)	11/357 (3.1%)
Cataract (Study eye)	15/357 (4.2%)
Conjunctival haemorrhage (Study eye)	24/357 (6.7%)
Dry eye (Fellow untreated eye)	19/357 (5.3%)
Dry eye (Study eye)	22/357 (6.2%)
Eye pain (Study eye)	25/357 (7%)
Eyelid oedema (Study eye)	9/357 (2.5%)
Glaucoma (Fellow untreated eye)	10/357 (2.8%)
Glaucoma (Study eye)	11/357 (3.1%)
Macular fibrosis (Study eye)	15/357 (4.2%)
Macular oedema (Study eye)	19/357 (5.3%)
Ocular discomfort (Study eye)	10/357 (2.8%)
Ocular hyperaemia (Study eye)	9/357 (2.5%)
Ocular hypertension (Fellow untreated eye)	8/357 (2.2%)
Ocular hypertension (Study eye)	26/357 (7.3%)
Vision blurred (Study eye)	18/357 (5%)
Visual acuity reduced (Study eye)	21/357 (5.9%)
Vitreous detachment (Study eye)	12/357 (3.4%)
Vitreous floaters (Study eye)	19/357 (5.3%)
Gastrointestinal disorders
Diarrhoea	11/357 (3.1%)
General disorders
Injection site pain (Study eye)	11/357 (3.1%)
Infections and infestations
Bronchitis	15/357 (4.2%)
Conjunctivitis (Fellow untreated eye)	8/357 (2.2%)
Conjunctivitis (Study eye)	10/357 (2.8%)
Influenza	17/357 (4.8%)
Lower respiratory tract infection	8/357 (2.2%)
Nasopharyngitis	39/357 (10.9%)
Pneumonia	8/357 (2.2%)
Sinusitis	9/357 (2.5%)
Tooth infection	9/357 (2.5%)
Upper respiratory tract infection	12/357 (3.4%)
Urinary tract infection	9/357 (2.5%)
Injury, poisoning and procedural complications
Fall	15/357 (4.2%)
Investigations
Intraocular pressure increased (Fellow untreated eye)	11/357 (3.1%)
Intraocular pressure increased (Study eye)	43/357 (12%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/357 (2.5%)
Back pain	13/357 (3.6%)
Nervous system disorders
Dizziness	11/357 (3.1%)
Headache	21/357 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	13/357 (3.6%)
Vascular disorders
Hypertension	40/357 (11.2%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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
Email

Responsible Party:

Novartis Pharmaceuticals

ClinicalTrials.gov Identifier:

NCT01535261

Other Study ID Numbers:

CRFB002E2401
2011-002350-31

First Posted:

Feb 17, 2012

Last Update Posted:

Oct 27, 2016

Last Verified:

Sep 1, 2016

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

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

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Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

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Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Certain Agreements

Results Point of Contact