PharmaSonics Inc has initiated a new European trial of its anti-restenotic Intravascular Sonotherapy therapeutic ultrasound system. The DiSPARKLE trial will examine the safety and efficacy of Sonotherapy treatment in diabetic patients to enhance the efficiency of drug-eluting stents. The study will also investigate the application of Sonotherapy treatment to the total coronary target vessel for the reduction of atherosclerotic disease progression, and for stabilizing vulnerable plaques that might develop within the non-stented segments of the target coronary artery.
The trial represents a significant broadening of the investigation of Sonotherapy treatment beyond the reduction of coronary restenosis into new and emerging applications as an adjunct to drug-eluting stents and for the stabilization of vulnerable plaques.
DiSPARKLE (Diabetics - Sonotherapy Prevention of Arterial Restenosis and Krappy Lesions), a randomized, double-blind study of 180 diabetic patients, will compare the use of Sonotherapy treatment versus sham control (i.e., placebo) in de novo coronary lesions. In the treatment group, Sonotherapy will be applied after implantation of drug-eluting stent(s) to the stented segment, as well as the proximal and distal segments.
The study will be limited to coronary arteries with diameters of 3.5mm or less. It will include multi-vessel stenting and Sonotherapy treatment lengths ranging from a minimum of 40mm to a maximum of 80mm.
The primary endpoint of the DiSPARKLE trial will be binary restenosis within the drug eluting stent as measured by Quantitative Coronary Angiography (QCA); other endpoints include one- and nine-month Major Adverse Cardiac Events (MACE). The endpoints for atherosclerotic disease progression will include angiographic assessment and MACE rates within the Sonotherapy-treated vessel segments outside the stent.
Menahem Nassi, PharmaSonics President and CEO, stated, "The initiation of the DiSPARKLE trial under Dr. Colombo''s leadership strengthens PharmaSonics'' Sonotherapy potential to participate in new and emerging interventional cardiology markets, as an adjunct to drug-eluting stents and as a treatment for vulnerable plaque. This is especially important in light of the anticipated release of the SWING trial results later this year, which we expect will establish the anti-restenotic efficacy of Sonotherapy when used in conjunction with bare stents."
The SWING trial aims to establish the nine-month safety and efficacy of Sonotherapy treatment for the reduction of restenosis rates in coronary de novo stented patients. SWING is a worldwide 1,200-patient, prospective, double-blind, randomized study. Patients were enrolled from Europe, U.S., Canada and South America.
The results of the EuroSPAH clinical trial, a European double-blind, multi-center randomized study of Sonotherapy treatment as anti-restenotic therapy in de novo stented patients, were reported recently at the 2002 European Society of Cardiology Congress by principal investigator Professor Patrick Serruys. Sonotherapy treatment after stenting reduced the re-intervention rate by 40% (p=0.045) at seven months when compared to stenting alone, the control arm.
The use of Sonotherapy to facilitate the drug delivery of drug-eluting stents is based on previous research in which ultrasound has been shown to increase membrane permeability and facilitate diffusion into tissue of therapeutic agents such as drugs, nucleic acid and genetic matter. The upcoming TCT 2002 meeting will include a presentation summarizing pre-clinical work in drug delivery recently conducted at the University of Sheffield, U.K. The study showed a fourfold increase in drug (DNA) uptake from drug-eluting stents by vascular smooth muscle cells with Sonotherapy treatment enhancing drug-delivery, compared to sham controls, which consisted of drug-eluting stents alone.
That Sonotherapy treatment may be effective in impacting atherosclerotic disease progression has been suggested in a pre-clinical study by Mark Post, of Dartmouth University. In his study, Sonotherapy treatment reduced hyperplasia area in iliac and femoral arteries of swine fed with a high-cholesterol diet lasting eleven weeks. Balloon arterial denudation injury was performed after 2 weeks from the start of the diet. Histological measurements were performed five days after Sonotherapy or sham treatments, applied one week after the end of the high cholesterol dietary regime.