Retinal Vein Occlusion
Conditions
Keywords
bevacizumab, ranibizumab, retinal vein occlusions, randomized clinical trial, Macular edema
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
Interventions
DRUGBevacizumab
1.25 mg bevacizumab administered by monthly interval for six months (6 injections).
DRUGRanibizumab
0.5mg ranibizumab administered by monthly interval for six months (6 injections).
Sponsors
Leiden University Medical Center
Free University Medical Center
Erasmus Medical Center
Radboud University Medical Center
UMC Utrecht
University Medical Center Groningen
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
1. Women of child-bearing potential. 2. 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); 3. Inability to comply with study procedures; 4. Active intraocular inflammation in either eye at enrolment; 5. Any active infection in either eye at the time of enrolment; 6. History of uveitis in either eye at any time; 7. 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; 8. Uncontrolled (neovascular) glaucoma in the study eye at screening. (IOP \> 24 mmHg on medication or according to investigator's judgment); 9. Evidence of vitreomacular traction in the study eye; 10. Patients who are monocular or have a Snellen VA in the non-study eye ≤ 1/300 at visit 1; 11. Any intraocular surgery in the study eye within 3 months prior to randomization; 12. Planned medical or surgical intervention during the 6-months study period; 13. Panretinal laser photocoagulation in the study eye within 3 months prior to or during the study; 14. Focal/grid laser photocoagulation in the study eye 3 months prior to study entry; 15. Treatment with anti-angiogenic drugs in the study eye within 3 months prior to randomization; 16. Use of other investigational drugs at the time of enrolment, or within 3 months or 5 half-lives from enrolment, whichever is longer; 17. History of intravitreal corticosteroids in study eye within 4 months prior to randomization; 18. Ocular conditions in the study eye that require chronic concomitant therapy with topical ocular or systemically administered corticosteroids; 19. History of stroke or transient ischemic attack (TIA) within 6 months prior to enrolment; 20. History of myocardial infarction within 3 months prior to randomization; 21. 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; 22. Known hypersensitivity to fluorescein, bevacizumab or ranibizumab or any component thereof or drugs of similar chemical classes; 23. 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; 24. 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); 25. Prior episode of RVO; 26. Evidence on examination of sight-threatening diabetic retinopathy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best corrected visual acuity | 6 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in leakage on fluorescein angiography | 6 months | The change in leakage on fluorescein angiography at the 6 month exit visit compared to baseline |
| Change in foveal thickness by optical coherence tomography | 6 months | The change in foveal thickness (central area thickness) by optical coherence tomography at 6 months compared to baseline |
| Proportion of patients with a gain or loss of 15 letters or more | 6 months | The proportion of patients with a gain or loss of 15 letters or more at 6 months compared to baseline BCVA |
| Costs per quality adjusted life-year of the two treatments | 6 months | 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 | 6 months | The proportion of patients with a BCVA of 20/40 or more at 6 months compared to baseline BCVA |
| The number of adverse events | 6 months | The number of adverse events that occurred in the time frame of 6 months and a classification of the type of adverse events |
Countries
Netherlands
Contacts
Primary ContactReinier O Schlingemann, PhD, MD
Backup ContactMonique -- Wezel
Outcome results
None listed