The only technology proven to be effective for treating in-stent restenosis is vascular brachytherapy. While this success is encouraging, there are a number of opportunities to improve outcomes. These include optimizing the dose of radiation and improving the design and position of the radiation source. Studies that address these concerns have the potential to improve outcome.

One study to address these potential improvements is BRITE II (Beta Radiation to Reduce In-Stent Restenosis). Investigators designed this study to test the feasibility, efficacy and safety of the RDX system, which incorporates a new balloon-shaped source design to deliver beta radiation.

The RDX system incorporates the beta-emitting P-32 beta-isotope into the balloon material with a three-layer, sealed source design. Investigators wanted to know if this particular system would produce an improved reduction in restenosis and revascularization rates.

The primary endpoint of the BRITE II trial is target vessel revascularization at 9 months. Investigators defined target vessel revascularization as any clinical revascularization of the target vessel using percutaneous coronary intervention or coronary artery bypass graft. Investigators also looked at a variety of safety and angiographic endpoints, including binary restenosis rate and late thrombosis or total occlusion.

The study included 460 patients (mean age 62 years) with in-stent restenosis. All patients received treatment with angioplasty and stenting. They were randomized in a 3-to-1 fashion to beta radiation delivery (360 patients) or placebo (120 patients). The dose of radiation was 20 Gy at 1 mm from the source.

Twenty-six U.S. centers contributed patients to the study.

All patients had a single restenotic lesion in a stent in a native coronary vessel. The degree of target vessel occlusion had to be greater than 50% but could not be total occlusion. Total lesion length was less than 45 mm.

Dr. Waksman presented the preliminary analysis of BRITE II data. The analysis suggested the treatment was safe. This was reflected in a procedural success rate exceeding 95%, a less than 1% rate of periprocedural complications, and a low incidence of 30-day major adverse clinical events (27% versus 43% for placebo, p=0.02).

The final analysis for efficacy is not complete. However, investigators did meet the study assumption that there would be a 42% reduction in target vessel revascularization. Target vessel revascularization at 9 months was 25% versus 43% (42% reduction, p=0.02). This compares favorably and is perhaps superior to historical data on the effect of vascular brachytherapy. In 3 different trials, vascular brachytherapy reduce target vessel revascularization versus placebo by about one-third.

In addition, there was a very low rate of in-stent restenosis in patients who received the beta radiation compared with placebo (10.9% versus 46.1%, p<0.001). This represents a 76% reduction in in-stent restenosis versus placebo.

Due to commercial considerations, the RDX system will probably not be released for marketing and clinical use. However, these findings confirm that vascular brachytherapy is useful and effective in the treatment of in-stent restenosis.

The company Endologix manufactured the RDX system and sponsored the BRITE II study. Investigators will present 12-month clinical follow-up data at a later time.