For the past year drug-eluting stents (DES) have raised concerns about blood clots, damaging sales of FDA-approved DES devices — in the U.S., the Taxus from Boston Scientific (Natick, Massachusetts) and the Cypher from Cordis (Miami, Florida), a unit of Johnson & Johnson (J&J; New Brunswick, New Jersey).

But long before this now-controversial class of products began making headlines, Medtronic (Minneapolis) was preparing for what it says is the largest randomized trial to focus on the safety of DES, a company spokesman told Cardiovascular Device Update.

Medtronic last month said it has enrolled the first patient in Patient Related OuTcomes with Endeavor versus Cypher stenting Trial (PROTECT), an 8,800-patient study that will pit Medtronic's Endeavor zotarolimus-eluting coronary stent system against the Cypher sirolimus DES, using key safety endpoints and other clinically relevant outcomes.

Medtronic said the first patient enrolled in PROTECT was implanted in Germany, by Johannes Brachmann, MD, of Klinikum Coburg (Coburg, Germany) and Christoph Bode, MD, of Universitätsklinikum (Freiburg, Germany).

The Endeavor DES received the CE mark in 2005, and it is now available in more than 100 countries, the company said. In the U.S. Endeavor is under review by the FDA.

Scott Papillon, a senior public relations manager for Medtronic, told CDU that the trial was designed to enroll 8,800 patients in order to create broad statistical significance.

"It's a first-of-its kind study," he said, "the first to go head-to-head with safety as a primary endpoint" - differentiating it from the many studies comparing rates of restenosis.

PROTECT is a response to the call for more long-term safety data, Papillon said, not necessarily a reaction to the controversy the products have sparked over the past year. "Doctors have been looking for long-term safety data for quite a while," Papillon said.

The primary endpoint for PROTECT will be overall stent thrombosis at three years, defined as definite and probable, according to the new Academic Research Consortium criteria. Secondary endpoints include a composite of death and non-fatal myocardial infarction, as well as numerous additional safety and clinical efficacy endpoints, the company said. The study will enroll patients at 200 clinical centers worldwide. The patients will represent the people typically seen by doctors on an everyday basis.

"We think no matter what definition you use, the Endeavor stent is exhibiting an excellent safety profile, and we think that will continue," Papillon said.

"PROTECT is a very important clinical trial for the interventional industry, as it is well-designed and adequately powered to provide the type of long-term safety data physicians have been seeking," said William Wijns, MD, co-director of the Cardiovascular Center, OLV Ziekenhuis (Aalst, Belgium) and co-principal investigator of PROTECT. "This trial should help offer greater clarity around the safety issues that have become part of the drug-eluting stent landscape. Patients and physicians are interested in the safety and efficacy performance of drug-eluting stents. This trial will provide the data which will be most relevant to daily clinical practice."

Elsewhere in the product pipeline:

• Boston Scientific (Natick, Massachusetts) reported two-year results from its RENAISSANCE study, which was designed to evaluate the safety and effectiveness of the company's Express SD Renal Stent in hypertensive patients with atherosclerotic renal artery stenosis (RAS). Results were presented at the All That Jazz conference in New Orleans. All patients in the study had a single, de novo RAS. The primary endpoint of the study was restenosis, or the re-narrowing of a previously stented vessel, at nine months. High technical and procedural success rates (99%) were achieved with excellent concordance (87%) between renal artery DUS and angiography for restenosis. The binary nine-month restenosis rate was 21.3%.

Boston Scientific also reported the enrollment of the first patient in the SONOMA post-market approval study of the company's NexStent carotid stent system used in conjunction with the FilterWire EZ embolic protection system. The objective of the study is to confirm the real-world safety and efficacy of the NexStent carotid stent system and FilterWire EZ embolic protection system in routine clinical practice. "This study represents one of the few multi-center studies in which shorter-term and longer-term clinical outcomes of carotid artery stenting placement will be reported," said Subbarao Myla, MD, principal investigator of the study. The FDA has approved the NexStent and FilterWire EZ for use in patients with carotid artery disease who are at high risk for surgical carotid endarterectomy. The NexStent includes a laser-cut, nitinol stent with a rolled sheet design that enables one stent size to adapt to multiple diameters in tapered or non-tapered vessel configurations. Its self-sizing feature is intended to provide customization when treating lesions in the carotid arteries, while its closed-cell configuration is designed to increase lesion coverage and to provide a smooth inner lumen to help facilitate delivery and retrieval of ancillary devices.

• Cook Medical (Bloomington, Indiana) reported the availability of the Cook Turbo-Flo 8 French Double Lumen Central Venous Catheter designed to produce increased flow rates. The catheter also employs Cook's patented antibiotic-impregnation process, infusing minocycline and rifampin on both the internal and external surfaces of the catheter to provide increased protection against catheter-related bloodstream infections. The Cook Turbo-Flo catheter's "double-D" lumen configuration provides maximum flow rates for whole blood product delivery and sampling or to deliver medication and nutrients. This catheter is introduced by minipuncture, marked by a smaller puncture site and a decrease in complications. Additionally, it is available with the Cook EchoTip echogenic needle to improve visibility by enhancing the needle's appearance during ultrasound imaging. The catheter is available in 15, 20 and 25 centimeter lengths and is now available with the Cook Full Spectrum tray, catheter tray and the cap, mask, gown and large drape maximum barrier precaution tray. Cook Medical makes interventional devices.

• Endosense (Geneva, Switzerland) reported the presentation of data as part of the abstract "Novel Radiofrequency Ablation Catheter with Contact Force Sensor Predicts Lesion Size and Incidence of Steam Pop in Canine Model" at the annual 2007 scientific sessions of the Heart Rhythm Society (Washington) in Denver. Tacticath, the Endosense catheter, demonstrated a statistically significant correlation between force and the key characteristics of the lesion: volume, depth, and surface. Since effective radio frequency lesion-making depends critically upon contact, real-time assessment of contact force is extremely important. Endosense assists in the adoption of percutaneous catheter ablation for the treatment of atrial fibrillation.

• Endovalve (San Francisco), developer of a percutaneous valve-replacement system to treat mitral regurgitation, said that it has developed a to-scale functional model of the valve and anchor design, successfully demonstrated important feasibility criteria and begun preclinical animal testing. "The functional 1x-scale model of the valve and anchor design, which is the linchpin of our mitral-valve replacement system, has successfully demonstrated such feasibility criteria as foldability and deployment of the nitinol and stainless steel device," resident/CEO Dr. Robert Wilkins told attendees here at the Medtech Insight Investment In Innovation (In3) Medical Device Summit. "Bench testing on slaughterhouse sheep hearts, has demonstrated that when the replacement valve drops from the left atrium into the native mitral valve, it pushes away the native leaflets and is seated in place. Endovalve is focused on developing a less invasive option for early treatment of mitral valve regurgitation. It was sSpun out of the University of Pennsylvania in spring 2006 with a $2.5-million investment from Battelle Ventures.

• ev3 (Plymouth, Minnesota) reported receiving a conditional Investigational Device Exemption (IDE) from the FDA to study the use of its Protege EverFlex Self-Expanding Stent System (EverFlex) in the treatment of peripheral artery disease (PAD). The trial, DURABILITY II, is designed to demonstrate the stent system's long-term patency and fracture resistance in symptomatic patients with PAD in the superficial femoral and proximal popliteal arteries of the leg. The study will include 30 clinical trial sites across the U.S. ev3 said that DURABILITY II will be the first trial in the treatment of PAD to explore single-stent treatment of lesions as long as 16 cm and will include five-year follow-up on stent fracture. It also will be the first study to follow the Performance Goal design, which was developed by VIVA Physicians (VPI) and published in the March 2007 issue of Catheterization and Cardiovascular Interventions.The EverFlex was designed specifically for use in the superficial femoral artery (SFA), where PAD is often present. It encompasses a spiral cell geometry constructed to withstand the movement of the SFA, and in bench testing has been demonstrated to be five to 10 times more durable than competitive stents. The EverFlex stent has been available in the U.S. since February 2006 for the palliative treatment of malignant neoplasms in the biliary tree. ev3 said it is conducting DURABILITY II with the objective of expanding the product's U.S. indication to include treatment of PAD.

• FoxHollow Technologies (Redwood City, California) reported plans to conduct a clinical study of its NightHawk Plaque Excision System under an Investigational Device Exemption application and to forego a previously 510(k) notification submitted to the FDA. Assuming FDA approval, FoxHollow said it hopes to begin a U.S. clinical study to gain "important insight and experience" evaluating the NightHawk's ability to estimate the location of the catheter to the vessel wall during peripheral plaque excision. It said that the 510(k) sought approval for "a more limited set" of claims. It said it believes that a clinical trial "will facilitate use of the device among a group of experienced SilverHawk users in the U.S." sooner than if it had waited for a 510(k) approval. The company said it hopes to begin trial enrollment in 3Q07. The NightHawk combines optical coherence tomography (OCT) with the company's FDA-cleared SilverHawk System. The SilverHawk Plaque Excision System is a minimally invasive method of removing obstructive plaque and restoring blood flow to the legs and feet. The NightHawk device utilizes fiber optic technology embedded in the catheter, allowing the physician to visualize the vascular morphology and wall structures within the artery. OCT imaging is designed for use as an adjunct to conventional angiography during plaque excision procedures. FoxHollow also markets the Rinspirator System for removing thrombus from occluded arteries in patients suffering from PAD or coronary artery disease.

• LeMaitre Vascular (Burlington, Massachusetts) has reported receiving FDA approval for an investigational device exemption supplement to conduct a pivotal trial, named UNITE, of its Aorto-Uni-Illiac Stent Graft. The graft would be a first for this indication, according to the company. The study will evaluate the safety and effectiveness of the company's UniFit Abdominal Stent Graft in the treatment of aorto and/or aorto-illiac aneurysms. LeMaitre added the device to its product pipeline when the company acquired Endomed (Phoenix), a maker of endovascular stent grafts for the minimally-invasive treatment of thoracic and abdominal aortic aneurysms, in 2005. The UniFit Abdominal Stent Graft is a single-bodied aorto-uni-iliac stent graft used to treat an aortic aneurysm, a weakening ballooning out of the aorta. It would be implanted through a minimally-invasive endovascular procedure. The device's encapsulated design prevents its stents from contacting the bloodstream or the vessel wall, which is designed to allow a wider range of stent graft sizes, including tapered and custom grafts. The primary endpoint for effectiveness of the study is based on aneurysm exclusion, which will be evaluated for one year following implantation of the device. LeMaitre previously received conditional FDA approval for its IDE supplement. "Although we had initiated two study sites based upon conditional approval, many other hospitals, though eager to participate, have been waiting for the FDA to remove conditions …," said George LeMaitre, the company's president/CEO and chairman in a statement. "We believe surgeons need a single-body aorto-uni-iliac stent graft to help combat aneursymal disease, and we are excited to begin implanting devices in our pivotal study."

• Luna Innovations (Roanoke, Virginia) said that it received FDA 510(k) clearance for its EDAC (emboli detection and classification) Quantifier, a cardiopulmonary bubble detector that uses quantitative ultrasound technology to non-invasively detect gaseous emboli in an extracorporeal bypass circuit line. Emboli can be air bubbles or solid matter, variable in their size and consistency, and can enter the extracorporeal blood circuit during invasive medical procedures such as cardiopulmonary bypass surgery. The Quantifier simultaneously monitors up to three bypass circuit locations, provides count rates up to at least 1,000 per second and detects emboli as small as 10 microns in diameter. The blood circuit monitor also provides real-time feedback and archived data on information such as emboli counts and volume estimates. Luna makes products for the healthcare, telecommunications, energy and defense markets.

• MedicalCV (Minneapolis) reported that its Solar Surgical Ablation System, cleared for use in the ablation or coagulation of soft tissue, has been used in its first clinical procedures. The first procedure was performed in conjunction with an open-heart mitral valve repair by Patrick McCarthy, MD, at Northwestern Memorial Hospital (Chicago). The second ablation was performed in conjunction with a minimally invasive mitral valve repair by Michael Caskey, MD, in Phoenix. McCarthy and Caskey both serve on MedicalCV's Scientific Advisory Board. Marc Flores, president/CEO of MedicalCV, said, "These procedures represent another significant milestone for MedicalCV and illustrate the value of developing our laser-based technology platform through ongoing collaboration between leadings physicians from both the academic and community settings and our engineering team." The company said that the Solar Surgical Ablation System was highlighted in presentations at both the Advanced Cardiac Techniques in Surgery and the American Association for Thoracic Surgery meetings, before nearly 1,000 physicians, held earlier this month. Solar and the company's Atrilaze system are based on MedicalCV's laser technology that delivers focused, coherent light energy for the purpose of creating deep, continuous lesions in surgical ablation. Solar recently received FDA 510(K) clearance with an indication for the delivery of laser light to soft tissue during surgical procedures.

• Micrus Endovascular (San Jose, California) reported market launch of its Cashmere microcoil system to treat complex cerebral aneurysms. The Cashmere is a platinum, stretch-resistant microcoil designed to provide stable framing or filling of aneurysms that may require a softer microcoil, such as those with irregular shapes or ruptured aneurysms.

Micrus also reported receiving FDA clearance for its ENZO steerable microcatheter. The ENZO is designed to offer improved maneuverability through the brain's tortuous vasculature and to enable in vivo repositioning of the microcatheter in the aneurysm, allowing physicians to more efficiently fill aneurysms. Micrus says that ENZO is the only steerable microcatheter available for use in the neurointerventional market. Micrus makes both implantable and disposable devices used in the treatment of cerebral vascular diseases.

The FDA reported approval of Evicel Fibrin Sealant, a liquid product, made by OMRIX Biopharmaceuticals (Kiryat Ono, Israel), that when applied topically helps control oozing from small blood vessels during surgical procedures. Jesse Goodman, MD, director of the agency's Center for Biologics Evaluation and Research, said, "Evicel provides an effective means to stop oozing from small vessels during vascular surgery when suturing, compression or other standard techniques are not effective or practical." Evicel is derived from pooled human plasma and consists of a fibrinogen concentrate and thrombin, two substances used to promote clotting. Both substances go through a two-stage process to reduce the risk of viral transmission in manufacturing. In a pivotal study of 147 patients, Evicel was compared with the standard bleeding control technique of applying pressure to a plastic covering (graft) placed over the open blood vessel. Of those who received Evicel, 83% stopped bleeding within four minutes, compared with 39.7% in the control group. Adverse events, such as anemia and graft site infection, were generally mild and occurred at about the same frequencies in the Evicel-treated group and the control group, according to the FDA. The agency originally licensed the predecessor of Evicel (Crosseal) in 2003 for use during liver surgery.

• Roche Diagnostics (Indianapolis), in cooperation with the FDA, announced that the Urgent Medical Device Correction issued for CoaguChek PT test strips (UMDC 06-266), used in anticoagulation monitoring, has been addressed and duplicate testing is no longer required for CoaguChek PT Test Strips, lot numbers 560A and higher (e.g., 561A, 562A, ...). The potential for erroneous prothrombin time (PT) test results that prompted the UMDC was a result of insufficient active ingredient (thromboplastin) on selected test strips. Fully tested and validated changes have been implemented within the manufacturing process to address this concern. All healthcare professionals performing duplicate testing to confirm results can return to a single test using CoaguChek PT Test Strips (only from lot numbers 560A and higher) to monitor patients on warfarin (anticoagulation) therapy. All patients previously performing patient self-testing may now resume monitoring with CoaguChek PT Test Strips (only from lot numbers 560A and higher). Roche is a research-focused healthcare group in the fields of pharmaceuticals and diagnostics.

• Royal Philips Electronics (Amsterdam, the Netherlands) reported release of Philips EP cockpit to support clinicians and staff in the treatment of cardiac rhythm disorders, including complex ablation therapies. This concept in electrophysiology (EP) labs combines Philips Allura Xper interventional lab with a number of other instruments to provide EP specialists with an efficient working environment to raise the level of heart rhythm care. The customizable lab setup includes video switching, single keyboard and mouse control concept and moveable ceiling suspended equipment rack holding EP lab equipment. Additionally, EP cockpit is equipped with an embedded data-management solution that can archive and retrieve patient data from various sources enabling physician access via a single workspace.

• Spectranetics (Colorado Springs, Colorado) said it has filed an FDA 510(k) application for the clearance of its Turbo-Booster product, a deflecting sheath that facilitates treatment of blockages in the popliteal artery and superficial femoral artery, the main arteries at or above the knee, and is used with Spectranetics' existing peripheral atherectomy laser catheters. Spectranetics says it makes the only excimer laser approved in the U.S., Europe and Japan for use in multiple, minimally invasive cardiovascular procedures.

• St. Jude Medical (St. Paul, Minnesota) reported FDA approval of four new devices. The Current ICD (implantable cardioverter defibrillator) and Promote CRT-D (cardiac resynchronization therapy defibrillator) are St. Jude's first devices to be built on the company's new consolidated hardware and software platform to support implantable cardiac devices. These products help treat patients with potentially lethal heart arrhythmias and heart failure. The CRT-D offers flexibility in pacing choices by allowing physicians to select an additional LV lead pacing pulse configuration. The Current ICD provides a delay in device stimulation of the lower chambers of the heart (ventricles) to allow the patient's own heart rhythm to prevail when possible. The OptiSense lead is described by St. Jude as a first-of-its-kind "smart" pacing lead designed to offer more accurate sensing in the upper chamber of the heart (right atrium). The lead uses a new tip design that reduces extraneous signals from the heart's lower chambers (ventricles) that can interfere with a pacemaker's sensing mechanism and disrupt optimal therapy. The OptiSense lead's improved sensing of desired electrical signals in the atria allows physicians more flexibility in programming atrial sensitivity settings while avoiding sensing signals from the ventricles. This allows for more accurate detection of impulses from the patient's atrium. The uni-directional therapy Cool Path open-irrigated ablation catheter is for use in patients with type 1 atrial flutter. Catheter ablation therapy is used by physicians to restore a normal heart rhythm in patients with cardiac arrhythmias. During the procedure, an electrophysiologist uses a catheter to deliver radiofrequency energy to create lesions in specific areas of cardiac tissue. The lesions, or tiny scars, interrupt the abnormal electrical signals that contribute to erratic heart rhythms. An open-irrigated catheter distributes saline fluid into heart tissue through ports in the tip of the catheter to enhance cooling during ablation procedures, reducing the risk of undesirable tissue damage at the procedure site.

• Thoratec (Pleasanton, California) said that it has completed enrollment in the randomized portion of the destination therapy (DT) arm of its pivotal trial for the HeartMate II by enrolling 200 patients on a randomized basis as called for in the trial protocol. The HeartMate II is a continuous flow device designed to provide long-term cardiac support for advanced-stage heart failure patients. An implantable left ventricular assist system powered by a rotary pumping mechanism, the HeartMate II is designed to have a much longer functional life than pulsatile devices and to operate more simply and quietly. The device provides blood flow through the circulatory system on a continuous basis with only one moving part. It is also smaller and easier to implant than pulsatile devices. Thoratec specializes in hemodynamic restoration therapy, developing products to treat cardiovascular disease.

• Toshiba America Medical Systems (Tustin, California) reported the completion of enrollment for 400 patients in its CorE 64 (Coronary Evaluation on 64) study taking place in seven countries, the largest trial ever initiated evaluating the use of 64-slice CT technology, the company said. The trial's enrollment completion signifies that the study of all patient participants has finished, resulting in the most statistically reliable data available to date. The trial investigates the use of multi-slice CT as the primary diagnostic tool for detecting cardiovascular diseases and disorders, as compared to cardiac catheterization, a costly, invasive technique. Toshiba America makes diagnostic imaging systems and coordinates clinical diagnostic imaging research for all modalities in the U.S.

• Ventracor (San Francisco) reported the presentation of summary clinical data of the first 100 patients implanted with the VentrAssist third generation left ventricular assist device (LVAD), an implantable blood pump designed for long term use in patients with advanced heart failure. The data was presented at a plenary session of the 2007 annual meeting of the International Society of Heart and Lung Transplantation (ISHLT). Ventracor makes an implantable blood pump, the VentrAssist left ventricular assist device, as therapy to improve the lives of heart failure patients and their families.

Separately, Ventracor reported the presentation of summary clinical data of the first 100 patients implanted with the VentrAssist third-generation left ventricular assist device (LVAD), an implantable blood pump designed for long term use in patients with advanced heart failure. The data was presented at a plenary session of the 2007 annual meeting of the International Society of Heart and Lung Transplantation (ISHLT). Ventracor makes an implantable blood pump, the VentrAssist left ventricular assist device, as therapy to improve the lives of heart failure patients and their families.

• VNUS Medical Technologies (San Jose, California) reported the launch of the VNUS ClosureFAST catheter, for the treatment of the underlying cause of varicose veins. ClosureFAST is an endovenous radiofrequency ablation catheter that is designed to heat, shrink and close diseased saphenous veins (large leg veins) in three to five minutes of RF treatment — as fast as laser ablation devices — with minimal pain and bruising. The entire ClosureFAST procedure, from insertion of the catheter to removal, can now be completed in approximately 16 minutes — less than half the time required for previous RF-based procedures. VNUS Medical Technologies makes products for the minimally invasive treatment of venous reflux disease.

• ZOLL Medical (Chelmsford, Massachusetts) reported receiving FDA clearance for its ZOLL E Series with See-Thru CPR technology. This CPR quality improvement benefit is provided by extracting the "artifact" (unwanted visual aberrations in the electrocardiograph (ECG) signal) caused by chest compressions. See-Thru CPR's processing technology actually extracts the CPR artifact and shows a "filtered" ECG on the defibrillator screen, allowing rescuers to see organized cardiac rhythm without stopping compressions. The American Heart Association notes that a primary source of interruption of CPR results from stopping to determine if an organized rhythm that can be defibrillated has developed. ZOLL Medical makes resuscitation devices and related software solutions.

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