Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)
Overview CATT Study
Comparison of Age-Related Macular Degeneration Treatments Trials (CATT)
Click on PDF at left for the complete CATT Manual of Procedures
The Comparisons of Age-Related Macular Degeneration Treatments Trials (CATT) is a multi-centered randomized clinical trial to assess the relative safety and efficacy of two treatments for subfoveal neovascular Age-Related Macular Degeneration (AMD), a disease that usually causes severe irreversible vision loss. CATT will be conducted in 44 clinical centers and is funded by the National Eye Institute.
The CPOB is home to both the CATT Coordinating Center and the Fundus Photograph Reading Center. The other resource centers are the Office of the Study Chair at Emory University and the Optical Coherence Tomography (OCT) Reading Center at Duke University.
WHAT IS NEOVASCULAR AMD AND WHY IS THE CATT STUDY IMPORTANT?
Age related macular degeneration (AMD) is the leading cause of severe vision loss in people over the age of 65 in the United States and other Western countries (Tielsch, 1994; Sommer, 1991; Leibowitz, 1980; Klein, 1992; Sorsby, 1966; Buch, 2001). More than 1.6 million people in the US currently have one or both eyes affected by the advanced stage of AMD (Friedman, 2002) and it is estimated that there are another 7 million individuals "at risk" (The Eye Diseases Prevalence Research Group 2004). Once advanced AMD occurs in one eye, the risk for developing advanced AMD in the second eye over a 5 year period is 43% (AREDS, 2001) and the impact is substantial; more than 230,000 people in the United States are believed to be legally blind due to AMD (Tielsch, 1994). In the US alone, the direct cost of illness associated with AMD is conservatively estimated at $10 billion annually. Because the incidence of AMD rises sharply with age, these numbers will multiply as the American population over the age of 65 increases. Projections by the US Census Bureau indicate the US population aged 65 years and older will increase 54% from 2000 to 2020 (US Census Bureau, 2002).
Most AMD-related blindness is attributable to neovascular form of the disease, known as choroidal neovascularization (CNV), which occurs when new, abnormal blood vessels develop in the macula. (The macula is responsible for central vision.) New treatments target these new vessels and try to prevent their development.
The CATT study is designed to evaluate the relative safety and efficacy of two drugs used to treat neovascular AMD on visual acuity and to evaluate how frequently the drugs should be administered.
In addition to determining which drug and treatment schedule is better in treating AMD, another important aspect of the CATT concerns the cost of these treatments. Using conservative estimates, the price differential between the treatments could be $26,800 per patient annually, yielding a savings to Medicare of up to $3 billion per year ($8.2 million per day)!
Current Treatments for Neovascular AMD
The latest treatments for neovascular AMD are designed to stop the growth of and leakage from abnormal blood vessels. These drugs are referred to anti-angiogenic drugs. (The word "angiogenesis" means the development of new blood vessels.) Drug treatment can help slow down vision loss from AMD and in some cases improve sight. The new drugs are injected into the vitreous of the eye, usually monthly.
In June 2006, the FDA approved Lucentis® for treating neovascular AMD. The regime used in the clinical trials showing the effectiveness of Lucentis® is an intravitreal injection every month. Lucentis® is the most effective treatment for neovascular AMD studied to date. However, before Lucentis® was approved and available, many ophthalmologists began using an almost identical drug, known as Avastin® to treat neovascular AMD. Avastin® is another anti-angiogenic drug that is approved by the FDA to treat certain cancers. This "off-label" use of Avastin® appeared to offer promising results similar to that of Lucentis®, but there has been no large, carefully controlled clinical trial to evaluate its effectiveness and safety for neovascular AMD.
The approval and availability of Lucentis® to treat neovascular AMD has not stopped interest in Avastin®, because there are considerable cost differences in the two therapies. A Lucentis® treatment costs approximately $2,000 per dose while an Avastin® treatment for AMD costs approximately $50-$100. Considering that the both drugs require multiple treatments, this cost differential is substantial.
In addition to the differences and similarities of the two drugs, the issue of dosing schedule is also of great interest. Widespread implementation of a fixed, every 4 week dosing schedule has obvious practical limitations and the cost of such repeated injections is considerable. Although the half-life of Avastin® may be longer than the half-life of Lucentis®, dosing as frequently as every 28 days with Avastin® may still be necessary to achieve the same beneficial effects as Lucentis®. Previous studies do not answer the question of whether a reduced dosing schedule is as effective as a fixed schedule of monthly injections. CATT is designed to do so.
CATT's primary outcome measure is change in visual acuity at one year. Secondary outcomes include
- Number of treatments
- 3-line change in visual acuity (15 letters on ETDRS chart)
- Change in subretinal and intraretinal fluid on OCT
- Change in lesion size on fluorescein angiography
- Incidence of complications of treatment (endophthalmitis, retinal detachment, cataract, uveitis)
- Cost of treatment
CATT Study Design
CATT will enroll 1200 participants aged 50 and older with subfoveal CNV secondary to AMD in at least one eye and visual acuity between 20/40 and 20/320, inclusive. The study eye must not have had any previous treatment for AMD. Click here to see complete eligibility requirements. Enrollment opened on February 1, 2008. CATT participants will complete a total of 24 monthly study visits for 2 years.
All participants are assigned randomly to one of 4 treatment groups.
1) Lucentis on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Lucentis every 4 weeks or to variable dosing.
2) Avastin on a fixed schedule of every 4 weeks for 1 year; at 1 year, re-randomization to Avastin every 4 weeks or to variable dosing.
3) Lucentis on variable dosing for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
4) Avastin on variable dosing for 2 years; i.e., after initial treatment, monthly evaluation for treatment based on signs of lesion activity.
CATT Clinical Centers:
CATT is conducted in 40-45 clinical centers in the U.S. Click here for a list of participating CATT clinical centers.
All CATT participants receive a study treatment at their initial visit and will have monthly study visits thereafter for two years. Those who are assigned to the fixed monthly dosing groups will receive treatment at every visit. Those who are assigned to variable dosing groups will be evaluated for treatment at every visit. If lesion activity is present, the participant will receive a study treatment.
Study visit procedures include established tests of visual acuity conducted by examiners masked to the treatment assignment, an examination by a CATT ophthalmologist, and retinal photographs and OCTs that are assessed by masked graders in a centralized reading centers The images provide a clinical picture of the severity of AMD. Click here to view all procedures that will occur during study visits.
CPOB's Role in CATT
CPOB staff members support both the Coordinating Center and the Photograph Reading Center for the CATT study. Click on the links to learn more about the services of the Coordinating Center and the Scheie Image Reading Center.
For more information on the CATT study, please contact Ellen Peskin.
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