Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (BRVO)

Retinal Vein Occlusion Clinical Trial

— BRVO  

Official title:

Comparing the Effectiveness and Costs of Bevacizumab to Ranibizumab in Patients With Retinal Vein Occlusions (The BRVO Study)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01635803
• Other study ID #: NL35869.018.11
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: June 28, 2012
• Last updated: June 30, 2015
• Start date: June 2012

Study information

• Verified date: June 2015
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: Reinier O Schlingemann, PhD, MD
• Phone: +31 20 5663682
• Email: r.schlingemann[@]amc.uva.nl
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: ZonMw, Netherlands Organisation for Health Research and Development
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 296
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Retinal Vein Occlusion

Intervention

Drug:
• Bevacizumab
1.25 mg bevacizumab administered by monthly interval for six months (6 injections).
• Ranibizumab
0.5mg ranibizumab administered by monthly interval for six months (6 injections).

Locations

Country	Name	City	State
Netherlands	Academic Medical Center, Dept. Ophthalmology	Amsterdam

Sponsors (7)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)	Erasmus Medical Center, Free University Medical Center, Leiden University Medical Center, Radboud University, UMC Utrecht, University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months	No
Secondary	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	6 months	No
Secondary	Change in leakage on fluorescein angiography	The change in leakage on fluorescein angiography at the 6 month exit visit compared to baseline	6 months	No
Secondary	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	6 months	No
Secondary	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	6 months	Yes
Secondary	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)	6 months	No
Secondary	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	6 months	No