SCORE investigators update, expand enrollment criteria

March 15, 2006

Madison, WI?Investigators expanded the eligibility criteria of the SCORE study, a multicenter, randomized clinical trial designed to investigate the safety and efficacy of standard care versus intravitreal triamcinolone acetonide (IVTA) injections for the treatment of macular edema associated with central and branch retinal vein occlusion. The broader standards will accommodate a patient population more closely matched to those seen in the practice setting.

Madison, WI-Investigators expanded the eligibility criteria of the SCORE study, a multicenter, randomized clinical trial designed to investigate the safety and efficacy of standard care versus intravitreal triamcinolone acetonide (IVTA) injections for the treatment of macular edema associated with central and branch retinal vein occlusion. The broader standards will accommodate a patient population more closely matched to those seen in the practice setting.

The enrollment began in November 2003. Michael S. Ip, MD, associate professor, ophthalmology and visual sciences, University of Wisconsin, Madison, and Ingrid U. Scott, MD, MPH, professor of ophthalmology and health evaluation sciences, Pennsylvania State University, Hershey, are principal investigators for the SCORE study.

"Investigators have seen patients that were perfect candidates for a comparison between standard of care and triamcinolone but because of the prior inclusion/exclusion criteria, they couldn't get those patients in," said Dr. Ip. "If these are the type of people that investigators need a comparison on, then the patient population in the SCORE study should reflect the relevant population. Therefore, we have amended the inclusion/exclusion criteria such that they mirror better the patient population that we actually need to study."

The old protocol required a 3-month duration minimum before a patient was enrolled; this was subsequently lowered to 2 months. Now patients can be enrolled as early as at the time of diagnosis. Also, there was an upper limit duration of 18 months of vein occlusion, but the duration has been expanded to 24 months.

The original intent was to avoid enrolling patients who might have spontaneous improvement, by requiring a duration of several months, Dr. Ip said. He added the intent was to exclude those patients with longstanding occlusions who would be extremely unlikely to have improvement after any intervention.

Investigators also made adjustments to visual acuity limits. Initially, the lower limit was 20/200, then 20/320, and more recently 20/400. The changes were made because several SCORE investigators have seen an improvement in patients with less than 20/200 vision through the use of intravitreal triamcinolone acetonide (Kenalog, Westwood Squibb), Dr. Ip explained.

The 7- to 21-day wait between random assignment and screening visits was changed so that patients can be screened and assigned on the same day.

The exclusion requirements pertaining to grid laser treatment were also altered. According to the original protocol, any history of prior laser treatment was an exclusion criterion. However, SCORE investigators noted that they frequently see patients on referral who have received some laser treatment for macular edema secondary to vein occlusion and who have persistent leakage and room for additional laser treatment, Dr. Ip said. Now, patients are eligible for the study if the laser treatment occurred at least 4 months before enrollment.

Investigational compound

The SCORE study, funded by the National Eye Institute, consists of two clinical trials, one each for central and branch retinal vein occlusion. Each compares standard of care with a 4-mg or 1-mg injection of IVTA. The enrollment goal is approximately 900 patients, and recruitment is ongoing.

The investigational compound, manufactured by Allergan, is preservative- and endotoxin-free and comes in a prepackaged sterile syringe designed for intraocular use. "These are the advantages of the formulation that's being used in the SCORE study as compared with the Kenalog formulation," Dr. Ip said.

IVTA is being used under an FDA Investigational New Drug Application.

Triamcinolone acetonide is approved for intramuscular and intrabursal use only, but for several years, the drug has been used in the eye on an off-label basis. The preservatives in the triamcinolone acetonide formulation could be disadvantageous if injected into the eye, so the IVTA formulation being used in the SCORE study does not include the preservatives, he added.

"Both central and branch retinal vein occlusion are relatively common conditions," Dr. Ip said. "There have been a number of new treatments proposed for both of these conditions in the recent past. Surgical options include radial optic neurotomy for central retinal vein occlusion and arteriovenous sheathotomy for branch retinal vein occlusion. Others include hemodilution therapy and injection of tissue plasminogen activator, both for central retinal vein occlusion."