A Study of the Safety and Efficacy of a New Treatment for Macular Edema Resulting From Retinal Vein Occlusion

• Sponsor: Allergan (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00168298
• Collaborator: (none)
• Enrollment: 668
• Locations: 13
• Arms: 3
• Actual Duration (Months): 46.1
• Patients Per Site: 51.4
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

This study will evaluate the safety and efficacy of an intravitreal implant of dexamethasone for the treatment of macular edema associated with retinal vein occlusion.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema; Retinal Vein Occlusion	Drug: 700 µg Dexamethasone; Drug: 350 µg Dexamethasone; Other: Sham Injection	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 668 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Actual Study Start Date: Nov 1, 2004
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Sep 5, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 700 µg Dexamethasone 700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180.	Drug: 700 µg Dexamethasone; 700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.; Other Names: Posurdex®
Experimental: 350 µg Dexamethasone followed by 700 µg Dexamethasone 350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180.	Drug: 700 µg Dexamethasone; 700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.; Other Names: Posurdex® ; Drug: 350 µg Dexamethasone; 350 µg Dexamethasone intravitreal implant administered on Day 0.; Other Names: Posurdex®
Sham Comparator: Sham Injection followed by 700 µg Dexamethasone Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180.	Drug: 700 µg Dexamethasone; 700 µg dexamethasone intravitreal implant administered on Day 0 and/or Day 180.; Other Names: Posurdex® ; Other: Sham Injection; Sham injection on Day 0.

Outcome Measures

Primary Outcome Measures

1. Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye [Day 180]

   BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. The numbers of patients with at least a 15 or more letter improvement in BCVA in the study eye are presented.

Secondary Outcome Measures

1. Change From Baseline in Retinal Thickness in the Study Eye [Baseline, Day 90, Day 180]

   Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement.

2. Percentage of Patients With a Change From Baseline in BCVA by Category [Baseline, Day 90]

   BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening.

3. Percentage of Patients With a Change From Baseline in BCVA by Category [Baseline, Day 180]

   BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• 18 years of age or older with macular edema resulting from retinal vein occlusion

• Decrease in visual acuity in at least one eye as a result of macular edema (20/50 or worse)

• Visual acuity in other eye no worse than 20/200

Key Exclusion Criteria:

• Known anticipated need for ocular surgery within next 12 months

• History of glaucoma or current high eye pressure requiring more than 1 medication

• Diabetic retinopathy

• Uncontrolled systemic disease

• Known steroid-responder

• Use of systemic steroids

• Use of warfarin/heparin

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Houston	Texas	United States
2		Sao Paulo		Brazil
3		Mississauga	Ontario	Canada
4		Bogota		Colombia
5		Kowloon		Hong Kong
6		Tamil Nadu		India
7		Udine		Italy
8		Seoul		Korea, Republic of
9		Auckland		New Zealand
10		Poznan		Poland
11		Singapore		Singapore
12		Alicante		Spain
13		London		United Kingdom

Sponsors and Collaborators

• Allergan

Investigators

• Study Director: Medical Director, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

• Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jacques ML, Jiao J, Li XY, Whitcup SM; OZURDEX GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010 Jun;117(6):1134-1146.e3. doi: 10.1016/j.ophtha.2010.03.032. Epub 2010 Apr 24.

• Responsible Party: Allergan
• ClinicalTrials.gov Identifier: NCT00168298
• Other Study ID Numbers: 206207-009
• First Posted: Sep 15, 2005
• Last Update Posted: Apr 23, 2019
• Last Verified: Apr 1, 2019

• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema; Dexamethasone; Dexamethasone acetate; BB 1101

Study Results

Participant Flow

Pre-assignment Detail	Patients were randomly assigned during the double-blind period of the study to treatment with 700 µg dexamethasone, 350 µg dexamethasone, or sham injection on Day 0. Patients who qualified to continue in the open-label period of the study received 700 µg dexamethasone on Day 180.

Arm/Group Title	700 µg Dexamethasone	350 µg Dexamethasone Followed by 700 µg Dexamethasone	Sham Injection Followed by 700 µg Dexamethasone
Arm/Group Description	700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180.	350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180.	Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180.
Period Title: Double-Blind Period
STARTED	226	218	224
COMPLETED	214	206	209
NOT COMPLETED	12	12	15
Period Title: Double-Blind Period
STARTED	179	173	168
COMPLETED	172	168	160
NOT COMPLETED	7	5	8

Baseline Characteristics

Arm/Group Title	700 µg Dexamethasone	350 µg Dexamethasone Followed by 700 µg Dexamethasone	Sham Injection Followed by 700 µg Dexamethasone	Total
Arm/Group Description	700 µg dexamethasone intravitreal implant administered on Day 0 and Day 180.	350 µg dexamethasone intravitreal implant administered on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180.	Sham injection on Day 0 and 700 µg dexamethasone intravitreal implant on Day 180.	Total of all reporting groups
Overall Participants	226	218	224	668
Age, Customized (participants) [Number]
<45 years	14 6.2%	15 6.9%	13 5.8%	42 6.3%
45-65 years	109 48.2%	108 49.5%	111 49.6%	328 49.1%
>65 years	103 45.6%	95 43.6%	100 44.6%	298 44.6%
Sex: Female, Male (Count of Participants)
Female	115 50.9%	102 46.8%	101 45.1%	318 47.6%
Male	111 49.1%	116 53.2%	123 54.9%	350 52.4%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With 15 or More Letter Improvement in Best Corrected Visual Acuity (BCVA) in the Study Eye
Description	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. The numbers of patients with at least a 15 or more letter improvement in BCVA in the study eye are presented.
Time Frame	Day 180

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone	350 µg Dexamethasone	Sham Injection
Arm/Group Description	700 µg Dexamethasone intravitreal implant administered on Day 0.	350 µg Dexamethasone intravitreal implant administered on Day 0.	Sham injection on Day 0.
Measure Participants	226	218	224
Number [Number of Participants]	53 23.5%	48 22%	38 17%

2. Secondary Outcome

Title	Change From Baseline in Retinal Thickness in the Study Eye
Description	Retinal thickness is assessed by optical coherence tomography (OCT) in the study eye. The retina is the light-sensitive part of the eye. OCT is a laser-based, noninvasive, diagnostic system providing high-resolution, three-dimensional images of the retina. A negative change from baseline indicates an improvement.
Time Frame	Baseline, Day 90, Day 180

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone	350 µg Dexamethasone	Sham Injection
Arm/Group Description	700 µg Dexamethasone intravitreal implant administered on Day 0.	350 µg Dexamethasone intravitreal implant administered on Day 0.	Sham injection on Day 0.
Measure Participants	226	218	224
Baseline	573.6 (189.08)	566.6 (219.63)	542.5 (185.64)
Change from Baseline at Day 90	-215.6 (207.62)	-205.5 (216.25)	-91.1 (191.85)
Change from Baseline at Day 180	-132.1 (207.20)	-150.5 (220.78)	-127.4 (197.77)

3. Secondary Outcome

Title	Percentage of Patients With a Change From Baseline in BCVA by Category
Description	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening.
Time Frame	Baseline, Day 90

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone	350 µg Dexamethasone	Sham Injection
Arm/Group Description	700 µg Dexamethasone intravitreal implant administered on Day 0.	350 µg Dexamethasone intravitreal implant administered on Day 0.	Sham injection on Day 0.
Measure Participants	226	218	224
≥15 Letters Improvement	21.2	25.7	13.8
≥5 and <15 Letters Improvement	45.1	39.0	37.1
No Change (Between -5 to +5 Letters)	25.7	26.6	29.9
≥5 and <15 Letters Worsening	4.4	6.4	11.2
≥15 Letters Worsening	3.5	2.3	8.0

4. Secondary Outcome

Title	Percentage of Patients With a Change From Baseline in BCVA by Category
Description	BCVA is measured using an eye chart and is reported as the number of letters read correctly (ranging from 0 to 100 letters). The lower the number of letters read correctly on the eye chart, the worse the vision (or visual acuity). An increase in the number of letters read correctly means that vision has improved. Data are grouped into the following 5 categories based on change from baseline: ≥15 Letters Improvement, ≥5 and <15 Letters Improvement, No Change (Between -5 to +5 Letters), ≥5 and <15 Letters Worsening, and ≥15 Letters Worsening.
Time Frame	Baseline, Day 180

Outcome Measure Data

Analysis Population Description

Intent-to-Treat: all randomized patients

Arm/Group Title	700 µg Dexamethasone	350 µg Dexamethasone	Sham Injection
Arm/Group Description	700 µg Dexamethasone intravitreal implant administered on Day 0.	350 µg Dexamethasone intravitreal implant administered on Day 0.	Sham injection on Day 0.
Measure Participants	226	218	224
≥15 Letters Improvement	23.5	21.6	17.0
≥5 and <15 Letters Improvement	35.0	33.9	28.6
No Change (Between -5 to +5 Letters)	27.0	28.9	28.6
≥5 and <15 Letters Worsening	8.0	10.6	13.8
≥15 Letters Worsening	6.6	5.0	12.1

Adverse Events

Time Frame	Adverse Events (AEs) and Serious Adverse Events (SAEs) are reported for the double-blind treatment period through Month 6.
Adverse Event Reporting Description	The safety population included all randomized patients who received at least one dose of study medication and was used to assess AEs and SAEs.
Arm/Group Title	700 µg Dexamethasone		350 µg Dexamethasone		Sham Injection
Arm/Group Description	700 µg Dexamethasone intravitreal implant administered on Day 0.		350 µg Dexamethasone intravitreal implant administered on Day 0.		Sham injection on Day 0.
All Cause Mortality
	700 µg Dexamethasone		350 µg Dexamethasone		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	700 µg Dexamethasone		350 µg Dexamethasone		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/225 (7.1%)		7/215 (3.3%)		17/221 (7.7%)
Cardiac disorders
Myocardial infarction	1/225 (0.4%)		1/215 (0.5%)		0/221 (0%)
Cardiac failure congestive	1/225 (0.4%)		0/215 (0%)		1/221 (0.5%)
Cardiac arrest	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Angina pectoris	0/225 (0%)		1/215 (0.5%)		0/221 (0%)
Angina unstable	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Congenital, familial and genetic disorders
Atrial septal defect	0/225 (0%)		1/215 (0.5%)		0/221 (0%)
Eye disorders
Ocular hypertension	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
General disorders
Non-cardiac chest pain	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Chest pain	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Hepatobiliary disorders
Cholecystitis	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Cholelithiasis	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Infections and infestations
Appendicitis	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Cellulitis	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Pneumonia	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Urinary tract infection	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Injury, poisoning and procedural complications
Foot fracture	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Investigations
Intraocular pressure increased	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Musculoskeletal and connective tissue disorders
Aneurysmal bone cyst	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Back pain	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Intervertebral disc degeneration	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/225 (0.4%)		1/215 (0.5%)		0/221 (0%)
Chronic lymphocytic leukaemia	0/225 (0%)		1/215 (0.5%)		0/221 (0%)
Prostate cancer	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Nervous system disorders
Carotid artery occlusion	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Cerebellar infarction	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Cerebrovascular accident	0/225 (0%)		1/215 (0.5%)		1/221 (0.5%)
Parkinson's disease	0/225 (0%)		1/215 (0.5%)		0/221 (0%)
Subarachnoid haemorrhage	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Renal and urinary disorders
Renal failure acute	1/225 (0.4%)		0/215 (0%)		1/221 (0.5%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Respiratory failure	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Haemothorax	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Pulmonary embolism	0/225 (0%)		0/215 (0%)		1/221 (0.5%)
Vascular disorders
Aortic aneurysm	1/225 (0.4%)		0/215 (0%)		0/221 (0%)
Other (Not Including Serious) Adverse Events
	700 µg Dexamethasone		350 µg Dexamethasone		Sham Injection
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	168/225 (74.7%)		145/215 (67.4%)		94/221 (42.5%)
Eye disorders
Conjunctival haemorrhage	46/225 (20.4%)		37/215 (17.2%)		37/221 (16.7%)
Conjunctival hyperaemia	18/225 (8%)		16/215 (7.4%)		13/221 (5.9%)
Eye pain	18/225 (8%)		10/215 (4.7%)		10/221 (4.5%)
Maculopathy	8/225 (3.6%)		15/215 (7%)		6/221 (2.7%)
Retinal exudates	6/225 (2.7%)		2/215 (0.9%)		12/221 (5.4%)
Investigations
Intraocular pressure increased	60/225 (26.7%)		56/215 (26%)		5/221 (2.3%)
Vascular disorders
Hypertension	12/225 (5.3%)		9/215 (4.2%)		11/221 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.