LUCAS (Lucentis Compared to Avastin Study)
Age-related macular degeneration (AMD) is the most common cause of blindness in individuals over 50 years of age. Bevacizumab and ranibizumab are two agents developed by the American pharmaceutical corporation Genentech, both of which inhibit blood vessel growth factors. These drugs, when injected intraocularly, reduce the pathological growth of blood vessels under the macula (the central area of the retina which is responsible for detailed vision). Bevacizumab (Avastin) is an antibody developed for intravenous treatment of metastasized colon cancer. Ranibizumab (Lucentis) is an antibody fragment developed from a similar antibody. It was introduced 2006 as an effective treatment for wet AMD. Treatment of wet AMD with Avastin has experimentally shown similar effects to ranibizumab, and has been used off-label in many countries, both before and after Lucentis received approval. Ranibizumab has, in controlled studies, been shown to be effective in improving vision in some patients, and to stop further visual loss in most patients. Treatment costs are, however, up to 50 times higher compared to use of bevacizumab, where a single vial can be used to prepare as many as 20 injections. Although the effects of Avastin have not been documented in large controlled studies, there are hundreds of articles published with regard to its effect and safety. Avastin has no formal approval for the indication AMD, but is used in many countries because of its effectiveness and low price. Such use has been criticized on the grounds of insufficient documentation. There is thus a recognized need for large randomized studies to garner proper scientific proof of Avastin's effectiveness regarding wet AMD.
This protocol describes such a randomized multicenter study, performed in Norway, comparing ranibizumab and bevacizumab use for AMD. The goal of the study is to demonstrate if the two agents are equivalent regarding both efficacy and safety. A total of 420 patients with objective evidence of wet AMD will be randomized to a double-blind treatment with ranibizumab or bevacizumab over the course of 2 years. The treatment interval will be determined by protocol called "inject and extend." The shortest interval will be 4 weeks and the longest 12 weeks. The goal of such a protocol is to determine an appropriate individual treatment regimen by gradually increasing the interval between injections. An extended interval between each examination and injection visit can reduce the burden upon an ophthalmology department, as well as increasing a patient's comfort. Such a protocol could also aid in reducing the risk of recurrence.
Wet Age-related Macular Degeneration
Drug: Bevacizumab (Avastin)
Drug: Ranibizumab (Lucentis)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Lucentis Compared to Avastin Study. A Randomized, Double Blind, Prospective Multicenter Study Comparing the Effect of Intravitreal Injection of Bevacizumab (Avastin)to Ranibizumab (Lucentis)When Given to Patients With Exudative (Wet) Age-related Macular Degeneration|
- Mean change in VA at 1 and 2 years as measured with the ETDRS chart [ Time Frame: After 1 and 2 years ] [ Designated as safety issue: No ]Mean change in VA at 1 and 2 years as measured with the ETDRS chart (with a non-inferiority limit of 5 letters)
- Number of treatments. [ Time Frame: After 1 and 2 years ] [ Designated as safety issue: No ]Number of treatments.
- Proportion of patients losing fewer than 15 letters on ETDRS chart [ Time Frame: After 1 and 2 years ] [ Designated as safety issue: No ]Proportion of patients losing fewer than 15 letters on ETDRS chart
- Macular morphology as measured by FA and OCT after 2 years. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]Macular morphology as measured by FA and OCT after 2 years.
- Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]Frequency of ophthalmological and other health related adverse events during the 2 year study.
- Number of non-responders. [ Time Frame: After 2 years ] [ Designated as safety issue: No ]Number of non-responders.
|Study Start Date:||March 2009|
|Estimated Study Completion Date:||July 2014|
|Estimated Primary Completion Date:||July 2013 (Final data collection date for primary outcome measure)|
|Active Comparator: Bevacizumab||
Drug: Bevacizumab (Avastin)
|Active Comparator: Ranibizumab||
Drug: Ranibizumab (Lucentis)
LUCAS (LUcentis Compared to Avastin Study) A randomized, double-blind, prospective multicenter study comparing the effect of intravitreal injection of bevacizumab (Avastin) to ranibizumab (Lucentis) when given to patients with exudative (wet) age-related macular degeneration in Norway.
Version: 4, Protocol: 166-09, EudraCT: 2008-004225-41
LUCAS is a prospective, randomized, multicenter study comparing the effects of intravitreal injection of bevacizumab (Avastin) with ranibizumab (Lucentis) when given to patients with exudative (wet) AMD in Norway.
The study will include 420 patients to be recruited starting March 2009. The study will continue for 2 years after completed enrollment.
LUCAS is a multicenter, randomized, double-blind study, with 1:1 parallel groups treated with either bevacizumab (Avastin) 0.05 ml (25 mg/ml) or ranibizumab (Lucentis) 0,05 ml (10 mg/ml). The drug is injected intravitreally according to an "inject and extend" principle (5).
Randomization will be stratified by center and performed with minimization according to prognostic factors.
Bevacizumab (Avastin) will be given as an intravitreal injection of 0.05ml (25 mg/ml) from a vial containing 4 ml.
Ranibizumab (Lucentis) will be given as an intravitreal injection of 0.05 ml (10 mg/ml) from a vial containing 0.23 ml.
Follow-up and treatment will follow a principle called "inject and extend." This connotes the following: initial follow-up and injection with a 4 week intervals until the macula is dry. When dry, then follow-up and injection will be increased 2 weeks at a time. If the patient has a recurrence of wet AMD, then the interval is reduced by 2 weeks at a time until the macula is once again dry. The shortest interval is 4 weeks. When once again extending, the treatment interval shall not be as long as the interval of the original recurrence, as this could confer risk for new activity. Therefore further follow-up and injection occurs at the "ideal" interval which is hereby defined as being 2 weeks less than that of the original recurrence. With this method, the patient receives an injection at each follow-up, presuming that no complications occur. The maximum interval is limited to 12 weeks. Treatment will continue for 2 years. After the study is completed, then the patient is to be offered continued treatment, in accordance with the ophthalmology department's routines, If there is no response to treatment after 3 injections with a 4 week interval, then the patient shall be removed from the study and be offered alternative treatment, such as combination treatment with photodynamic therapy (PDT).
|Department of Ophthalmology, Oslo University Hospital|
|Oslo, Norway, 0407|
|Study Director:||Andreas Moan||Director of Research at Oslo University Hospital|
|Study Chair:||Ragnheidur Bragadottir, MD. PhD.||Department of Ophthtalmology, Oslo University Hospital|
|Principal Investigator:||Karina Berg, MD.||Department of Ophthalmology, Oslo University Hospital|
|Study Chair:||Terje Pedersen, Professor||Department of Preventative Medicine, Oslo University Hospital|