Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (BRVO) (BRVO)
Primary Purpose
Retinal Vein Occlusion
Status
Unknown status
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Bevacizumab
Ranibizumab
Sponsored by
About this trial
This is an interventional treatment trial for Retinal Vein Occlusion focused on measuring bevacizumab, ranibizumab, retinal vein occlusions, randomized clinical trial, Macular edema
Eligibility Criteria
Inclusion Criteria:
- Male or female patients > 18 years of age with vision loss due to foveal center-involved ME secondary to branch or central retinal vein occlusion diagnosed within 6 months before study initiation, who have signed an informed consent;
- BCVA equal or more than 24 and less or equal to 78 letters in the study eye at screening using ETDRS- like visual acuity testing charts at a testing distance of 4 meters
- Mean central subfield thickness more than 275 micron on 2 OCT measurements.
Exclusion Criteria:
- Women of child-bearing potential.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test (human chorionic gonadotropin > 5 mIU/ml);
- Inability to comply with study procedures;
- Active intraocular inflammation in either eye at enrolment;
- Any active infection in either eye at the time of enrolment;
- History of uveitis in either eye at any time;
- Structural damage within 600 micron of the center of the macula in the study eye likely to preclude improvement in visual acuity following in the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques;
- Uncontrolled (neovascular) glaucoma in the study eye at screening. (IOP > 24 mmHg on medication or according to investigator's judgment);
- Evidence of vitreomacular traction in the study eye;
- Patients who are monocular or have a Snellen VA in the non-study eye ≤ 1/300 at visit 1;
- Any intraocular surgery in the study eye within 3 months prior to randomization;
- Planned medical or surgical intervention during the 6-months study period;
- Panretinal laser photocoagulation in the study eye within 3 months prior to or during the study;
- Focal/grid laser photocoagulation in the study eye 3 months prior to study entry;
- Treatment with anti-angiogenic drugs in the study eye within 3 months prior to randomization;
- Use of other investigational drugs at the time of enrolment, or within 3 months or 5 half-lives from enrolment, whichever is longer;
- History of intravitreal corticosteroids in study eye within 4 months prior to randomization;
- Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids;
- History of stroke or transient ischemic attack (TIA) within 6 months prior to enrolment;
- History of myocardial infarction within 3 months prior to randomization;
- Current use of or likely need for systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine (Plaquenil), tamoxifen, phenothiazines and ethambutol;
- Known hypersensitivity to fluorescein, bevacizumab or ranibizumab or any component thereof or drugs of similar chemical classes;
- Any type of advanced, severe or unstable disease or its treatment, that may interfere with primary and/or secondary variable evaluations including any medical condition that could be expected to progress, recur, or change to such an extend that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk;
- Ocular disorders in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 6 month study period, including cataract, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularisation of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia);
- Prior episode of RVO;
- Evidence on examination of sight-threatening diabetic retinopathy.
Sites / Locations
- Academic Medical Center, Dept. OphthalmologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Ranibizumab
Bevacizumab
Arm Description
Monthly injections with ranibizumab during 6 months
Monthly injections with bevacizumab during 6 months
Outcomes
Primary Outcome Measures
Best corrected visual acuity
The primary outcome is the change in best-corrected visual acuitiy (BCVA) in the study eye from baseline to month 6 assessed with EDTRS-like VA charts at an initial distance of four meter.
Secondary Outcome Measures
Proportion of patients with a gain or loss of 15 letters or more
The proportion of patients with a gain or loss of 15 letters or more at 6 months compared to baseline BCVA
Change in leakage on fluorescein angiography
The change in leakage on fluorescein angiography at the 6 month exit visit compared to baseline
Change in foveal thickness by optical coherence tomography
The change in foveal thickness (central area thickness) by optical coherence tomography at 6 months compared to baseline
The number of adverse events
The number of adverse events that occurred in the time frame of 6 months and a classification of the type of adverse events
Costs per quality adjusted life-year of the two treatments
The costs per quality adjusted life-year of the two treatments, results will be based on the use of standardized health questionnaires (EQ5D or HUI3)
The proportion of patients with a BCVA of 20/40 or more
The proportion of patients with a BCVA of 20/40 or more at 6 months compared to baseline BCVA
Full Information
NCT ID
NCT01635803
First Posted
June 28, 2012
Last Updated
June 30, 2015
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Leiden University Medical Center, Free University Medical Center, Erasmus Medical Center, Radboud University Medical Center, UMC Utrecht, University Medical Center Groningen
1. Study Identification
Unique Protocol Identification Number
NCT01635803
Brief Title
Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (BRVO)
Acronym
BRVO
Official Title
Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (The BRVO Study)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Unknown status
Study Start Date
June 2012 (undefined)
Primary Completion Date
June 2016 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
Leiden University Medical Center, Free University Medical Center, Erasmus Medical Center, Radboud University Medical Center, UMC Utrecht, University Medical Center Groningen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary objective is to demonstrate the non-inferiority of bevacizumab in the treatment of patients with macular edema secondary to a retinal vein occlusion (branch or central) as determined by the change in best-corrected visual acuity in the study eye from baseline to month 6.
Detailed Description
Objective: to compare the effectiveness and costs of 1.25 mg bevacizumab to 0.5 mg ranibizumab, given as monthly intravitreal injections during 6 months.
Study Design: This will be a randomized, controlled, double masked, clinical trial in 296 patients in 7 academic trial centres in The Netherlands.
Study population: patients older than 18 years of age with macular edema secondary to a retinal vein occlusion and a best corrected visual acuity (BCVA) score between 78 and 20 letters in the study eye.
Outcomes: The primary outcome measure will be the change in BCVA in the study eye from baseline to month 6.
Secondary outcomes will be amongst others the proportion of patients with a gain of 15 letters or more and/or a BCVA of 20/40 or more at 6 months and the costs per quality adjusted life-year of the two treatments
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Retinal Vein Occlusion
Keywords
bevacizumab, ranibizumab, retinal vein occlusions, randomized clinical trial, Macular edema
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
296 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ranibizumab
Arm Type
Active Comparator
Arm Description
Monthly injections with ranibizumab during 6 months
Arm Title
Bevacizumab
Arm Type
Active Comparator
Arm Description
Monthly injections with bevacizumab during 6 months
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
1.25 mg bevacizumab administered by monthly interval for six months (6 injections).
Intervention Type
Drug
Intervention Name(s)
Ranibizumab
Other Intervention Name(s)
Lucentis
Intervention Description
0.5mg ranibizumab administered by monthly interval for six months (6 injections).
Primary Outcome Measure Information:
Title
Best corrected visual acuity
Description
The primary outcome is the change in best-corrected visual acuitiy (BCVA) in the study eye from baseline to month 6 assessed with EDTRS-like VA charts at an initial distance of four meter.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Proportion of patients with a gain or loss of 15 letters or more
Description
The proportion of patients with a gain or loss of 15 letters or more at 6 months compared to baseline BCVA
Time Frame
6 months
Title
Change in leakage on fluorescein angiography
Description
The change in leakage on fluorescein angiography at the 6 month exit visit compared to baseline
Time Frame
6 months
Title
Change in foveal thickness by optical coherence tomography
Description
The change in foveal thickness (central area thickness) by optical coherence tomography at 6 months compared to baseline
Time Frame
6 months
Title
The number of adverse events
Description
The number of adverse events that occurred in the time frame of 6 months and a classification of the type of adverse events
Time Frame
6 months
Title
Costs per quality adjusted life-year of the two treatments
Description
The costs per quality adjusted life-year of the two treatments, results will be based on the use of standardized health questionnaires (EQ5D or HUI3)
Time Frame
6 months
Title
The proportion of patients with a BCVA of 20/40 or more
Description
The proportion of patients with a BCVA of 20/40 or more at 6 months compared to baseline BCVA
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female patients > 18 years of age with vision loss due to foveal center-involved ME secondary to branch or central retinal vein occlusion diagnosed within 6 months before study initiation, who have signed an informed consent;
BCVA equal or more than 24 and less or equal to 78 letters in the study eye at screening using ETDRS- like visual acuity testing charts at a testing distance of 4 meters
Mean central subfield thickness more than 275 micron on 2 OCT measurements.
Exclusion Criteria:
Women of child-bearing potential.
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum pregnancy test (human chorionic gonadotropin > 5 mIU/ml);
Inability to comply with study procedures;
Active intraocular inflammation in either eye at enrolment;
Any active infection in either eye at the time of enrolment;
History of uveitis in either eye at any time;
Structural damage within 600 micron of the center of the macula in the study eye likely to preclude improvement in visual acuity following in the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s), epiretinal membrane involving fovea or organized hard exudate plaques;
Uncontrolled (neovascular) glaucoma in the study eye at screening. (IOP > 24 mmHg on medication or according to investigator's judgment);
Evidence of vitreomacular traction in the study eye;
Patients who are monocular or have a Snellen VA in the non-study eye ≤ 1/300 at visit 1;
Any intraocular surgery in the study eye within 3 months prior to randomization;
Planned medical or surgical intervention during the 6-months study period;
Panretinal laser photocoagulation in the study eye within 3 months prior to or during the study;
Focal/grid laser photocoagulation in the study eye 3 months prior to study entry;
Treatment with anti-angiogenic drugs in the study eye within 3 months prior to randomization;
Use of other investigational drugs at the time of enrolment, or within 3 months or 5 half-lives from enrolment, whichever is longer;
History of intravitreal corticosteroids in study eye within 4 months prior to randomization;
Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids;
History of stroke or transient ischemic attack (TIA) within 6 months prior to enrolment;
History of myocardial infarction within 3 months prior to randomization;
Current use of or likely need for systemic medications known to be toxic to the lens, retina or optic nerve, including deferoxamine, chloroquine/hydroxychloroquine (Plaquenil), tamoxifen, phenothiazines and ethambutol;
Known hypersensitivity to fluorescein, bevacizumab or ranibizumab or any component thereof or drugs of similar chemical classes;
Any type of advanced, severe or unstable disease or its treatment, that may interfere with primary and/or secondary variable evaluations including any medical condition that could be expected to progress, recur, or change to such an extend that it may bias the assessment of the clinical status of the patient to a significant degree or put the patient at special risk;
Ocular disorders in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the 6 month study period, including cataract, retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularisation of any cause (e.g., AMD, ocular histoplasmosis, or pathologic myopia);
Prior episode of RVO;
Evidence on examination of sight-threatening diabetic retinopathy.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reinier O Schlingemann, PhD, MD
Phone
+31 20 5663682
Email
r.schlingemann@amc.uva.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Monique -- Wezel
Phone
+31 205663616
Email
m.wezel@amc.uva.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reinier O Schlingemann, MD, PhD
Organizational Affiliation
Academic Medical Center, Dept. Ophthalmology, Room A2-122, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
Official's Role
Principal Investigator
Facility Information:
Facility Name
Academic Medical Center, Dept. Ophthalmology
City
Amsterdam
ZIP/Postal Code
1105 AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Reinier O Schlingemann, MD, PhD
Phone
+31 205663682
Email
r.schlingemann@amc.uva.nl
First Name & Middle Initial & Last Name & Degree
Monique Wezel
Phone
+31 205663616
Email
m.wezel@amc.uva.nl
First Name & Middle Initial & Last Name & Degree
Reinier O Schlingemann, MD, PhD
12. IPD Sharing Statement
Learn more about this trial
Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (BRVO)
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