RETAIN: Extended Follow-up of Patients With Macular Edema Due to Retinal Vein Occlusion

• Sponsor: Peter A Campochiaro, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT01198327
• Collaborator: The Macula Foundation, Inc. (Other), Genentech, Inc. (Industry)
• Enrollment: 66
• Locations: 6
• Arm: 1
• Duration (Months): 28
• Patients Per Site: 11
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study evaluates long-term safety in patients with macular edema due to Retinal Vein Occlusion (RVO) originally enrolled in the BRAVO & CRUISE trials and subsequently followed in the HORIZON extension trial.

Condition or Disease	Intervention/Treatment	Phase
Retinal Vein Occlusion	Drug: ranibizumab; Other: Peripheral Laser	Phase 3

Detailed Description

There is strong evidence that ranibizumab provides benefit in subjects with macular edema due to RVO; however, some subjects required continued injections for years to maintain those benefits. It is likely that such subjects have continued production of VEGF (Vascular Endothelial Growth Factor) from areas of nonperfused retina in the periphery. One strategy is to perform scatter photocoagulation to areas of nonperfusion to reduce continued production of VEGF, but it is important to know if visual benefits are maintained when this is done, because if it is not, it would be better to continue intermittent injections of ranibizumab.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Extended Follow-up of Patients With Macular Edema Due to bRanch rETinal Vein Occlusion (BRVO) or centrAl Retinal veIn occlusioN (CRVO) Previously Treated With Intravitreal Ranibizumab
• Study Start Date: Aug 1, 2010
• Actual Primary Completion Date: Dec 1, 2012
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ranibizumab as needed Intravitreal ranibizumab, .5mg dose, PRN but not less than 21 days apart; with optional peripheral laser to areas of non-perfusion.	Drug: ranibizumab; Intravitreal ranibizumab, .5mg dose, PRN but not less than 21 days apart.; Other Names: RBZ, lucentis ; Other: Peripheral Laser; Areas of nonperfusion identified on wide field angiograms will receive laser, if the patient is continuing to require ranibizumab injections.; Other Names: Laser

Outcome Measures

Primary Outcome Measures

1. Incidence of Serious Adverse Events. [24 mos]

   Record the serious adverse events, both ocular and non-ocular to gather long-term safety data.

Secondary Outcome Measures

1. Mean Changes in Visual Acuity [24 mos from study baseline]

   Mean changes in visual acuity. Visual acuity is measured using standard ETDRS (Early Treatment Diabetic Retinopathy Study) charts which measure visual acuity in terms of letters( ETDRS Letters) read at a distance of 4 meters away from the chart. The ETDRS letters Score can be from 0 to 100, with 0 representing poor vision and 100 representing best vision.

2. Mean Change in Retinal Thickness [24 mos from study baseline]

   Mean change in retinal thickness as measured by OCT (Optical Coherence Tomography).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Signed informed consent and authorization of use and disclosure of protected health information

• Age greater than or equal to 18 years

• Completion of 12 months in BRAVO or CRUISE trials, with subsequent follow-up in the HORIZON extension study. Exit from HORIZON should be within 90 days of enrollment

Exclusion Criteria:

• Pregnancy (positive pregnancy test) or lactation

• Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.

• Any condition that the investigator believes would pose a significant hazard to the subject if investigational therapy were initiated.

• Inability to comply with study or follow up procedures

• Participation in another simultaneous medical investigation or trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Retina-Vitreous Associates Medical Group	Beverly Hills	California	United States	90211
2	Retinal Consultants Medical Group	Sacremento	California	United States	95819
3	Southeast Retina	Augusta,	Georgia	United States	30909
4	Ophthalmic consultants of Boston	Boston	Massachusetts	United States	02114-2587
5	Retina Associates of New Jersey	Teaneck	New Jersey	United States	07666
6	Retina Consultants of Houston	Houston	Texas	United States	77030

Sponsors and Collaborators

• Peter A Campochiaro, MD
• The Macula Foundation, Inc.
• Genentech, Inc.

Investigators

• Principal Investigator: Peter A Campochiaro, MD, Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Campochiaro PA, Hafiz G, Channa R, Shah SM, Nguyen QD, Ying H, Do DV, Zimmer-Galler I, Solomon SD, Sung JU, Syed B. Antagonism of vascular endothelial growth factor for macular edema caused by retinal vein occlusions: two-year outcomes. Ophthalmology. 2010 Dec;117(12):2387-2394.e1-5. doi: 10.1016/j.ophtha.2010.03.060. Epub 2010 Jul 13.
• Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG; BRAVO Investigators. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1102-1112.e1. doi: 10.1016/j.ophtha.2010.02.021. Epub 2010 Apr 15.

• Responsible Party: Peter A Campochiaro, MD, Principal Investigator, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT01198327
• Other Study ID Numbers: NA_00040287
• First Posted: Sep 10, 2010
• Last Update Posted: Jan 13, 2014
• Last Verified: Nov 1, 2013

• Keywords provided by Peter A Campochiaro, MD, Principal Investigator, Johns Hopkins University: RVO; CRVO; BRVO; Horizon; Bravo; Cruise
• Additional relevant MeSH terms: Macular Edema; Retinal Vein Occlusion; Ranibizumab

Study Results

Participant Flow

Recruitment Details	66 retinal vein occlusion patients from the HORIZON study(NCT01198327)were enrolled from 7 sites for long term follow up. The sites were: Wilmer Eye Institute, Ophthalmic Consultants of Boston, Retina Consultants of New Jersey, Retina Consultants Macula Group,Retina Consultants of Houston, Southeast Retina and Retina Vitreous Associates

Arm/Group Title	Ranibizumab as Needed
Arm/Group Description	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion.
Period Title: Overall Study
STARTED	66
COMPLETED	56
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Ranibizumab as Needed
Arm/Group Description	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion.
Overall Participants	66
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	23 34.8%
>=65 years	43 65.2%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.9 (10.8)
Sex: Female, Male (Count of Participants)
Female	28 42.4%
Male	38 57.6%
Region of Enrollment (participants) [Number]
United States	66 100%

Outcome Measures

1. Primary Outcome

Title	Incidence of Serious Adverse Events.
Description	Record the serious adverse events, both ocular and non-ocular to gather long-term safety data.
Time Frame	24 mos

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab as Needed
Arm/Group Description	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion.
Measure Participants	66
Number [number of serious adverse events]	17

2. Secondary Outcome

Title	Mean Changes in Visual Acuity
Description	Mean changes in visual acuity. Visual acuity is measured using standard ETDRS (Early Treatment Diabetic Retinopathy Study) charts which measure visual acuity in terms of letters( ETDRS Letters) read at a distance of 4 meters away from the chart. The ETDRS letters Score can be from 0 to 100, with 0 representing poor vision and 100 representing best vision.
Time Frame	24 mos from study baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab as Needed -CRVO	Ranibizumab as Needed -BRVO
Arm/Group Description	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion. CRVO stands for Central retinal vein occlusion.	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion. BRVO stands for branch retinal vein occlusion.
Measure Participants	28	28
Mean (Standard Deviation) [ETDRS letters]	14.0 (20.9)	20.1 (17.2)

3. Secondary Outcome

Title	Mean Change in Retinal Thickness
Description	Mean change in retinal thickness as measured by OCT (Optical Coherence Tomography).
Time Frame	24 mos from study baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ranibizumab as Needed -CRVO	Ranibizumab as Needed -BRVO
Arm/Group Description	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion. CRVO stands for central retinal vein occlusion.	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion. BRVO stands for branch retinal vein occlusion.
Measure Participants	28	28
Mean (Standard Deviation) [microns]	-426.0 (270.1)	-236.2 (230.3)

Adverse Events

Arm/Group Title	Ranibizumab as Needed
Arm/Group Description	Ranibizumab as needed, with optional peripheral laser to areas of non-perfusion.
All Cause Mortality
	Ranibizumab as Needed
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Ranibizumab as Needed
	Affected / at Risk (%)	# Events
Total	17/66 (25.8%)
Cardiac disorders
ECG for elective knee surgery showed inverted T waves, patient asymptomatic, admitted for workup	1/66 (1.5%)	1
Mild chest discomfort for 6 mos, coronary angiography showed 2 obstructions	1/66 (1.5%)	1
Tachycardia and went to the emergency department	1/66 (1.5%)	1
Syncope with fall because of arrhythmia	1/66 (1.5%)	1
Eye disorders
Vitreous hemorrhage,	1/66 (1.5%)	1
Second branch retinal vein occlusion in same eye	1/66 (1.5%)	1
Retinal tear in a patient with branch retinal vein occlusion who did not receive any treatment	1/66 (1.5%)	1
Severe reaction to povidon-iodine	1/66 (1.5%)	1
General disorders
Death resulting from pre-existing idiopathic pulmonary fibrosis	1/66 (1.5%)	1
Death of unknown cause	1/66 (1.5%)	1
Chronic atrial fibrillation, CVA; bladder cancer identified during hospitalization	1/66 (1.5%)	1
Head injury resulting from fall	1/66 (1.5%)	1
Infections and infestations
Urinary tract infection leading to septic shock	1/66 (1.5%)	1
Hospitalized for pneumonia	2/66 (3%)	3
Musculoskeletal and connective tissue disorders
Hospitalized for elective surgery	2/66 (3%)	3
Other (Not Including Serious) Adverse Events
	Ranibizumab as Needed
	Affected / at Risk (%)	# Events
Total	53/66 (80.3%)
Eye disorders
Ocular discomfort	13/66 (19.7%)	15
Subconjuctival Hemorrhage	13/66 (19.7%)	21
Vitreous Hemmorhage	7/66 (10.6%)	8
General disorders
Upper Respiratory Infection	20/66 (30.3%)	26

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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.