Clinical trial NCT01635803: Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (BRVO)
Official title: Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (The BRVO Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Retinal Vein Occlusion
Keywords: bevacizumab
ranibizumab
retinal vein occlusions
randomized clinical trial
Macular edema
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
Collaborators: name: Leiden University Medical Center
name: Free University Medical Center
name: Erasmus Medical Center
name: Radboud University Medical Center
name: UMC Utrecht
name: University Medical Center Groningen
First posted: 2012-07-10
Enrollment: 296
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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:

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.

Primary outcomes:
measure: Best corrected visual acuity
timeFrame: 6 months
Secondary outcomes:
measure: Proportion of patients with a gain or loss of 15 letters or more
timeFrame: 6 months
measure: Change in leakage on fluorescein angiography
timeFrame: 6 months
measure: Change in foveal thickness by optical coherence tomography
timeFrame: 6 months
measure: The number of adverse events
timeFrame: 6 months
measure: Costs per quality adjusted life-year of the two treatments
timeFrame: 6 months
measure: The proportion of patients with a BCVA of 20/40 or more
timeFrame: 6 months
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center, Dept. Ophthalmology
Study officials:
affiliation: Academic Medical Center, Dept. Ophthalmology, Room A2-122, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
name: Reinier O Schlingemann, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: