Cordis (Miami Lakes, Florida), a Johnson & Johnson (New Brunswick, New Jersey) company, last month received a unanimous recommendation, with conditions, for approval of its radiation treatment of in-stent restenosis from the Circulatory System Devices Panel of the FDA, the first such approval for this type of therapy. Cordis' Checkmate – full name the Checkmate Gamma Brachytherapy System – is an intravascular radiation system being developed for the specific application of restenosis treatment. In-stent restenosis occurs because some patients have scar-like tissue build-up around the stent. The Checkmate was designed for these most difficult patients, according to Cordis.
"This is the first radiation system approved [by an FDA panel] for cardiology treatment," said Cordis spokesperson Jeff Swearingen. "We have had a very positive efficacy, with 640 patients involved in trials so far. The FDA seems comfortable with our data," he told Cardiovascular Device Update. During the procedure, doctors use a catheter to thread a radiation-emitting device inside the artery during an angioplasty. The emitted radiation works to stop the production of clog-forming cells.
The panel said that the FDA will require more data for this new use of radiation and has placed some conditions on the product. The FDA's cardiovascular chief, James Dillard, noted that the studies showed that the radiation helped keep arteries open for six to nine months. But the agency is still concerned that the procedure might cause heart attacks as well as prevent them, and is asking for at least five years of follow-up data on recipients to settle this question. "Even with the conditions [imposed by the FDA], we still expect final approval of Checkmate by the end of the year," Swearingen said.
The company also will be required to provide more informative labeling, especially concerning the risks of the product to pregnant women and prior radiation patients. The FDA also noted that the procedure will require a specialized team of doctors, and that this should be explained.
The specially trained team includes an interventional cardiologist, a radiation oncologist and a physicist. Initially, the doctors perform an angioplasty to open up the occluded artery. A catheter is then inserted that contains six to 10 seeds of Iridium 192, a low-dose radiation, that catheterizes the target site and prevents clog-forming cells from reforming. The dosage time for the radiation ranges from eight to 20 minutes, and the entire procedure should take no longer than an hour to perform. "So far we have three-year success rates that are based on our earliest human trials," said Swearingen. "It is only natural that FDA would require more data, especially since this a new procedure."
In its FDA submission, the company cited six-month angiographic results of three landmark single- and multi-center randomized clinical trials. Results from these trials demonstrated a significant reduction in both angiographic and clinical in-stent restenosis vs. placebo, as well as reduced MACE (major adverse clinical events). In regard to reimbursement, Swearingen said that Cordis still had to prove the value of Checkmate over repeated angioplasty and stenting procedures to the Health Care Financing Administration, but, he added, "I don't think anyone will question the value of a procedure like this over major bypass surgery. We are going forward with private providers at this time." Checkmate already has CE mark approval and it has been launched in Italy, Germany, the Netherlands and Belgium. Launch is still pending in the United Kingdom. Checkmate has been in development since 1993.
Cordis is just one of several companies scrambling to win approval for the use of radiation for this application. Among these are Novoste (Norcross, Georgia), Cook (Bloomington, Indiana), Guidant (Indianapolis, Indiana), Boston Scientific (Natick, Massachusetts), Endosonics (Rancho Cordova, California), Implant Sciences (Wakefield, Massachusetts), IsoStent (Belmont, California), Pharmacyclics (Sunnyvale, California), Pharmasonics (Sunnyvale, California) and Radiance Medical Systems (Irvine, California).
Among the most recent developments in this area have been Novoste's FDA submission of its premarket approval application in April for its Beta-Cath system, supported by data from a 476-patient trial. In May, Radiance Medical launched its Phase I BRITE (BETA Radiation to Reduce In-Stent Restenosis) study of its RDX Coronary Radiation Delivery Catheter System, and in early June it said it was expanding that trial to broader patient populations. And in mid-June Implant Sciences announced, in conjunction with the Cleveland Clinic Foundation (Cleveland, Ohio), the launch of animal studies of its radiation system which contains Phosphorous-32 on the stent body with a spike of Palladium-103 activity at each end.
Elsewhere in the product pipeline:
Acuson (Mountain View, California) has received pass-through Medicare reimbursement status for the AcuNav Diagnostic Ultrasound Catheter from the Health Care Financing Administration (HCFA; Baltimore, Maryland) under the Medicare and Medicaid Prospective Payment System. The HCFA C class code (C1001) has been assigned to the catheter for ambulatory procedures, enabling hospitals that use the company's catheter to receive reimbursement for the product in an amount that is based on the individual hospital's charge for the device. The AcuNav catheter provides visualization of heart structures, devices within the heart and the measurement of blood flow, and may aid in the diagnosis and management of heart disease and irregular heart rhythms, according to the company. The intracardiac ultrasound technique works by inserting a catheter through the femoral vein of the leg or the jugular vein in the neck, then maneuvering it into the right atrium or right ventricle of the heart. The sensitivity of the catheter enables it to acquire diagnostic images and Doppler blood flow information throughout the entire heart. Results of the clinical trial submitted by the company to the FDA indicated that target cardiac structures were seen with diagnostic quality 100% of the time, according to Acuson.
Angiosonics (Morrisville, North Carolina) has begun two multicenter cardiovascular clinical studies in Europe: the TURBO Trial (The Ultrasound Removal of Blood ClOts in VeinGrafts) and the Acolysis for Acute Myocardial Infarction Trial (a European ATLAS Registry). Both studies will assess the benefits of ultrasound thrombolysis for coronary indications using the Acolysis System. Their results, according to the company, will support data already collected from two European studies. Reports of past experience with the Acolysis System for coronary syndromes indicate that ultrasound thrombolysis provides complete clot dissolution while controlling distal embolization. Angiosonics makes therapeutic ultrasound technologies for a variety of indications.
Cardima (Fremont, California) said that, based on results of its Phase I and Phase II studies of its Revelation Tx microcatheter system, the FDA has approved initiation of a Phase III of an ongoing trial to treat paroxysmal atrial fibrillation. Up to 128 additional patients may be enrolled in the study, at 15 sites. To date 47 patients have been treated at nine centers in Phase I and Phase II.
CardioTech International (Woburn, Massachusetts) has started its preclinical evaluation of a radioactive sleeve that reduces or eliminates scar tissue (anastomotic hyperplasia) that forms around implanted synthetic coronary artery grafts and the aorta. The sleeves are being implanted in experimental animals for periods of up to six weeks. The preclinical study is being conducted by CardioTech, Implant Sciences and Stanford University Medical Center, with funding coming from a government grant. Bypass graft surgery using saphenous veins from the patient is limited because of long-term failure due to anastomotic hyperplasia. Synthetic grafts suffer from a similar failure. CardioTech's thin, bioresorbable polymer sleeve contains radioactive phosphorous to deliver a continuous radiation at the anastomosis for inhibition of hyperplasia. CardioTech also said it has completed clinical studies and has applied for the CE mark for its second-generation Vasculink Vascular Access graft coated with heparin, a natural anticoagulant that acts to prevent unwanted clotting inside the graft during surgical implantation. The heparin is covalently bonded onto the graft's inner surface by means of a patented process licensed to CardioTech for vascular grafts by PolyBiomed (Sheffield, United Kingdom). The company says that this advanced bonding technique permits heparin to remain pharmacologically active for up to three weeks, compared to a few hours for current heparin coatings. CardioTech expects to complete the CE marking process for the graft in the third quarter. CardioTech also said it has received a U.S. patent titled "Hydrophilic and Hydrophobic Polyether Polyurethanes and Uses Therefor," covering amphiphilic polymers used for controlled delivery systems.
Fusion Medical Technologies (Fremont, California) said that the results of a randomized study comparing the effectiveness of its FloSeal matrix hemostatic sealant with that of gelfoam plus thrombin in controlling bleeding during cardiac surgery have been published in the Annals of Thoracic Surgery (Vol. 69, issue 5). Data from the four-center, 93-patient study showed that bleeding stopped completely within 10 minutes in 94% of patients treated with FloSeal, compared to 60% of patients treated with gelfoam plus thrombin. For bleeding sites categorized as "heavy," hemostasis was achieved at three minutes in 77% of the cases with FloSeal compared to none with gelfoam plus thrombin.
Guidant (Indianapolis, Indiana) has received FDA marketing clearance for two new coronary dilatation catheters. The company said these catheters incorporate significant technological advancements for angioplasty procedures while offering the smallest profiles of any coronary dilatation catheter currently available. The CrossSail Coronary Dilatation Catheter has a rapid-exchange design which, the company said, allows physicians to use the sole operator technique preferred, due to ease of use and faster procedure time. Its over-the-wire counterpart, the OpenSail Coronary Dilatation Catheter, allows physicians who prefer the over-the-wire design to use this more familiar technique. The CrossSail was launched throughout the U.S. last month, while the launch of the OpenSail will begin upon completion of the CrossSail rollout. Guidant also said it has begun a clinical trial to evaluate the efficacy of its Multi-Link Pixel Coronary Stent System designed to treat threatened abrupt closures of first-time or recurring blockages in small vessels. Patrick Bergin, MD, implanted the stent in a small-diameter vessel in danger of closing during a percutaneous transluminal coronary angioplasty (PTCA) procedure at Sacred Heart Medical Center (Eugene, Oregon). A PTCA procedure uses a coronary dilatation catheter to crack and compress the plaque against the artery wall, which helps restore natural blood flow. On occasion, the dilated artery does not remain open after the dilatation catheter is removed, placing the patient at risk for abrupt vessel closure, the most common complication following PTCA. John Capek, PhD, president of Guidant's Vascular Intervention Group, said the company "is hopeful that this important clinical trial will establish the Multi-Link Pixel Coronary Stent as an effective, minimally invasive means of preventing the dangerous complications that result from small-vessel closures."
Integra LifeSciences Holdings (Plainsboro, New Jersey) has launched its Rivetti-Levinson IntraLuminal Shunt which, according to the company, will reduce intraoperative ischemia and improve construction of coronary artery bypass grafts in the beating heart. The shunt provides direct, or "pass-through," perfusion to the distal artery while surgical anastomosis is performed. Supplemental blood flow also can be delivered by connecting the perfusion side limb of the shunt to any source of arterialized blood using a standard Luer connection. The shunt provides a variety of options for the surgeon, comes in multiple sizes and provides a bloodless field with minimal or no ischemia while the grafts are being constructed, the company says.
IntraTherapeutics (St. Paul, Minnesota) has received FDA 510(k) clearance to market a new stent length of the IntraCoil Bronchial Self-Expanding Nitinol Endoprosthesis. The IntraCoil is now available in both 40 mm and 60 mm stent lengths. The 60 mm IntraCoil comes in 4 mm to 7 mm stent diameters on a 135 cm catheter. IntraTherapeutics also is conducting an IDE clinical trail on the IntraCoil for a superficial femoral artery and popliteal indication. IntraTherapeutics is a privately held company that makes devices for the treatment of vascular disease and non-vascular obstructions.
Meridian Medical (Columbia, Maryland) reported receiving a U.S. patent, including 18 claims, for a key element of its Prime ECG electrocardiac mapping system, which it said has been found in European studies to diagnose heart attacks and related disorders earlier and with greater accuracy than a traditional 12-lead ECG. The patent covers the Prime ECG disposable sensor device allowing fast, anatomically correct placement of large numbers of electrodes, the company said. Featuring 80 screen-printed electrodes on clear plastic strips, the sensor device is placed around the torso. The company said that the newly patented sensor unit can be rapidly and accurately positioned on the body, regardless of body size and shape. The electrodes are incorporated in a disposable vest of clear plastic strips, resulting in an increased diagnostic detection area that records heart signals from 64 anterior and 16 posterior sensors for a more complete view of the heart's electrical activity. Meridian said it has launched the Prime ECG electrocardiac mapping system in Italy through its marketing partner in that country, Medico SpA (Rubano, Italy). The company said that the technology has been found in European studies to detect heart attacks earlier and more accurately than traditional ECG systems. The ECG mapping system already has received CE mark approval, allowing sales in all European Union countries. In addition to Medico SpA, Meridian has entered marketing agreements for the Prime ECG system with Medipro in Spain and Portugal, Kivex in Denmark, and Cardiac Mapping Systems in Australia. The company sells direct in the United Kingdom.
Spectranetics (Colorado Springs, Colorado) has completed Phase I enrollment for the company's Laser Angioplasty for Critical Ischemia (LACI) trial. The LACI study involves four enrolling sites and 25 patients in the U.S. The purpose of the study is to evaluate the use of excimer laser technology to treat limb-threatening vascular blockages below the knee, and the company said it will request expansion of the study to Phase II. Spectranetics makes excimer laser technology for interventional cardiovascular procedures.
St. Jude Medical (St. Paul, Minnesota) unveiled its new 6 Fr Spyglass angiography catheters for international marketing. Spyglass catheters are used in coronary angiography procedures to obtain images of coronary arteries to identify structural cardiac diseases. The 6 Fr Spyglass catheters incorporate flat wire braiding technology. This, according to the company, provides excellent torque control for easy manipulation of the catheter and an extra-large inner lumen to enable high flow rates of the contrast media, permitting the visualization of cardiac structures.
Thoratec Laboratories (Pleasanton, California) has submitted a 510(k) application to the FDA for its Vectra Vascular Access Graft, designed to provide access to the bloodstream in end-stage renal disease patients undergoing hemodialysis. Included in the company's filing is an analysis of the 142 patients enrolled in the U.S. clinical trial, six-month data on the primary cohort and a post market requirement for one-year follow-up. If the FDA accepts the data, the company said it expects to receive approval to begin marketing the device in the U.S. by the end of the year. If the FDA requires additional follow-up, the company said it would refile the submission in 4Q00. The Vectra graft has been available in Japan, Australia and Canada for several years, and is currently being rolled out in Europe by Guidant, which has exclusive worldwide marketing and distribution rights to the Vectra, except in Japan.
Vascular Solutions (Minneapolis, Minnesota) has received FDA marketing clearance for its Duett sealing device. The device combines a balloon catheter delivery mechanism with a biological procoagulant mixture which, according to the company, enables cardiologists and radiologists to rapidly seal the puncture site following catheterization procedures such as angiography, angioplasty and stenting. The Duett provides a way to rapidly seal the femoral arterial puncture site and thereby improve patient outcomes and comfort.