|- candidate number||3334|
|- NTR Number||NTR1331|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||29-mei-2008|
|- Secondary IDs||MEC 08-2-037 |
|- Public Title||The EQUAL study|
|- Scientific Title||The EQUAL study: A randomised trial to study the EQUivalence of three monthly intravitreal injections and additional injections as needed of bevacizumab (Avastin ®) and ranibizumab (Lucentis ® ) on visual acuity in patients with exudative age-related macular degeneration. |
|- ACRONYM||The EQUAL study|
|- hypothesis||Intravitreal injections of bevacizumab and ranibizumab are equally effective on visual acuity in patients with age-related macular degeneration.|
|- Healt Condition(s) or Problem(s) studied||Exudative age-related macula degeneration (ARMD), Bevacizumab , Intravitreal injection, Ranibizumab|
|- Inclusion criteria||1. Patients 60 years of age or higher. |
2. Patients with primary or recurrent sub-, juxta- or extrafoveal CNV secondary to AMD, including those with RAP, that may benefit from anti-VEGF treatment in the opinion of the investigator.
3. The total area of CNV (including both classic and occult components) encompassed within the lesion must be more or equal to 30% of the total lesion area.
4. The total lesion area should be < 12 disc areas.
5. A best corrected visual acuity (BCVA) score between 78 and 20 letters (approximately 0,63-0,05 Snellen equivalent) in the study eye.
6. Willing and able to give written informed consent according to legal requirements, and who have signed the consent form prior to initiation of any study procedure.
|- Exclusion criteria||1. Ocular treatment with anti-angiogenic drugs in the last 2 months or Triamcinolone or Prednisolone in the last 6 months.|
2. Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within one month preceding Baseline.
3. Patients with angioid streaks or precursors of CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia.
4. Spherical equivalent of refractive error in the study eye demonstrating more than – 8 dioptres of myopia.
5. Cataract extraction within three months preceding Baseline.
6. IOP >25 mm Hg
7. Active intraocular inflammation in the study eye.
8. Vitreous haemorrhage obscuring view of the posterior pole in the study eye.
9. Presence of a retinal pigment epithelial tear involving the macula in the study eye.
10. Subretinal haemorrhage in the study eye if the size of the haemorrhage is > 70% of the lesion
11. Subfoveal fibrosis or atrophy in the study eye.
12. History of hypersensitivity or allergy to fluorescein.
13. Inability to obtain fundus photographs, fluorescein angiograms or OCT’s of sufficient quality to be analyzed and graded by the Central Reading Centre.
14. Systemic disease with a life expectancy shorter than the duration of the study.
15. Inability to adhere to the protocol with regard to injection and follow-up visits.
16. Legally incompetent adult
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-jul-2008|
|- planned closingdate||1-jul-2011|
|- Target number of participants||284|
|- Interventions||Three monthly intravitreal injections and additional injections as needed during one year of: |
Group A: 1.25 mg bevacizumab
Group B: 0.5 mg ranibizumab
|- Primary outcome||The change in best-corrected visual acuity (BCVA) in the study eye from baseline to Month 12 assessed with ETDRS-like VA charts at an initial distance of four meter. |
The VA will be measured at baseline and once a month during one year.
|- Secondary outcome||- The proportion of patients with a loss of BVCA less than 15 letters from Baseline at 12 months (responders)|
- The proportion of patients with a loss or gain of BVCA less than 15 letters from Baseline at 12 months (stabilizers)
- The proportion of patients with 15 letters loss or more of BCVA from Baseline at 12 months (losers)
- The proportion of patients with 15 letters gain or more of BCVA from Baseline at 12 months (gainers)
- The change in quality of life and utility from baseline to 3, 6 and12 months
- The incidence of fluorescein leakage at 12 months as well as the change in total area of CNV, total area of leakage from CNV, and total lesion area from baseline at 12 months
- Absolute and percent change in retinal thickness, as measured by optical coherence tomography (OCT) at 4 and 12 months
- Proportion of dropouts before the final 12 months assessments
- Proportion of non-responders at the 4 month assessment
- The occurrence of (serious) adverse events during the 12 months of the study
- Costs of the two treatment stategies.
|- Timepoints||Follow up of patients will be performed each month during one year. The first three months patients receive three monthly injections. Thereafter during a monthly follow up visit the need for additional injections will be assessed based on OCT and visual acuity.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Dr. J.S.A.G. Schouten|
|- CONTACT for SCIENTIFIC QUERIES||Dr. J.S.A.G. Schouten|
|- Sponsor/Initiator ||University Hospital Maastricht (AZM)|
(Source(s) of Monetary or Material Support)
|ZON-MW, The Netherlands Organization for Health Research and Development|
|- Brief summary||Rationale: |
Exudative age-related macular degeneration (exudative AMD) is the main cause of untreatable blindness in The Netherlands and other western countries, and a major burden for the elderly population. Since February 2007, an expensive breakthrough drug, ranibizumab, has become available. Ranibizumab is able to stabilize or improve vision in the majority of patients with exudative AMD, but the costs of this treatment may rise to over 60 million Euro in the Netherlands alone. While Ranibizumab awaited approval, ophthalmologists have treated patients with a related drug, bevacizumab (Avastin). In three RCT’s and 23 large case series bevacizumab appears to have the same efficacy and safety as ranibizumab. The costs of bevacizumab are negligible compared to those of ranibuzimab and given the suggested efficacy, it has become a widely used off-label drug for the treatment of exudative AMD. In the absence of randomized controlled trials showing conclusive evidence, the use of bevacizumab is questioned now that ranibizumab has become available, unless bevacizumab will be shown to be as effective as ranibuzimab.
The primary objective is to compare the efficacy of intravitreal bevacizumab to intravitreal ranibizumab on visual acuity in exudative age related macular degeneration to show non-inferiority. Secondary objectives are to compare the costs and quality of life.
Randomized, double masked, clinical trial
284 patients with exudative age related macular degeneration and subgroups based on fluoresceine angiography and genetic polymorphisms
1.25 mg of bevacizumab or 0.5 mg ranibizumab, given as three times monthly injections and as needed thereafter during a total of 12 months after inclusion
Main study parameters/endpoints:
Primary outcome measure will be the mean change in best-corrected visual acuity (BCVA) in the study eye from baseline to Month 12.
Secondary outcomes are
- the proportions of patients with a gain of 15 letters or more and/or a BCVA of 20/40 or more at 12 months,
- the change in leakage and lesion size on fluoresce in angiography at 12 months and change in foveal thickness by optical coherence tomography at 6 and 12 months
- the type and number of adverse events in 12 months
- the mean change in quality of life from baseline to 12 months
- and the costs and costs per quality adjusted life-year of the two treatments.
|- Main changes (audit trail)|
|- RECORD||29-mei-2008 - 25-jul-2008|