Though the majority of panel members praised the PAS-Port technology – and more than one called it “impressive” and even “ingenious” – a lack of data offered by Cardica (Redwood City, California) may keep the FDA from clearing a 510(k) for the company’s proximal anastomosis device.
Cardica’s PAS-Port is designed to create an anastomosis between a large target vessel, such as the aorta, and a conduit, such as a venous conduit. Anastomosis refers to a surgical connection between two structures – most commonly between tubular structures such as blood vessels – and the PAS-Port is intended as a less-invasive alternative to suturing during coronary bypass surgery.
The Circulatory System Devices Panel of the FDA made no formal vote on the device at its late-April meeting, but panelists’ comments clearly will serve to recommend against approval. Cardica won CE-marking for the PAS-Port almost two years ago, and it is distributed in Europe by Guidant (Indianapolis), which has invested roughly $14 million in Cardica over the past two years.
At the panel meeting, the company presented combined data from two separate trials, both conducted outside the U.S. The first study was a 55-patient, prospective, single-arm trial. The second study included data from a 54-patient cohort from a trial originally intended to evaluate Cardica’s C-Port distal anastomotic connector.
The panel expressed concern that the data supporting the PAS-Port application was compiled retrospectively from a subset of patients in the second trial, originally designed to evaluate another product. Some patients during the C-Port trial also received PAS-Port devices at surgeons’ discretion. Panelists argued that pooling data was not enough to address the limitations of the first trial. They also raised questions regarding safety data and changes to product labeling.
Elsewhere in the product pipeline:
• Abiomed (Danvers, Massachusetts) moved a step closer to an approval for its experimental artificial heart with the disclosure that the FDA will convene an expert panel of cardiovascular surgeons and cardiologists to consider the company’s humanitarian device exemption (HDE) submission. The special expert review panel is slated to decide on June 23 on the potential approval for the AbioCor what the company has billed as “the first-ever completely self-contained artificial heart to come before the FDA for review.” The company originally filed its HDE application with the FDA last September. Javier Jimenez, vice president of operations, told CDU that if Abiomed gets its HDE for the device it will do a “very controlled rollout, with only up to 15 centers that will be doing procedures with this device.” After that, he said the company plans to focus its attention on the next-generation AbioCor II device, which already has been implanted in animals and is slated for clinical implantation in humans by the end of 2007. The newer iteration of the device will be 35% smaller and is projected to be a five-year device vs. the two years projected for the original system.
• AGA Medical (Minneapolis) said it would present an update on its RESPECT clinical trial, plus an in-depth examination of the issues facing clinicians who treat patent foramen ovale (PFO) patients affected by stroke, during a symposium at the Society for Cardiac Angiography and Interventions annual scientific sessions in Ponte Vedra Beach, Florida. The RESPECT (Randomized Evaluation of Recurrent Stroke comparing PFO Closure to Established Current Standard of Care Treatment) trial is designed to investigate whether transcatheter closure of PFO using the company’s implantable Amplatzer PFO Occluder is superior to standard of care medical treatment in preventing recurrent stroke or transient ischemic attack in patients with PFO. RESPECT was the first trial of its kind unconditionally approved by the FDA, the company said. The study includes 45 investigational sites that will enroll up to 500 patients. Patients are randomized so that half are implanted with the Amplatzer PFO Occluder and half receive one of four standard medical therapy regimens.
• Angiotech Pharmaceuticals (Vancouver) reported positive preliminary safety results for its Vascular Wrap paclitaxel-eluting mesh trial. This first-in-man study is designed to evaluate the safety and performance of the Vascular Wrap in preventing stenosis after peripheral bypass surgery. The wrap is applied around the anastomosis site of a synthetic bypass graft and delivers drug to the blood vessel wall to prevent or reduce the renarrowing of an artery that typically follows this surgery, Angiotech said. The study randomized patients with peripheral vascular disease in a 2:1 fashion, the treatment arm enrolling patients with a synthetic bypass graft plus the Vascular Wrap mesh, the control arm enrolling patients with a synthetic bypass graft alone. Preliminary assessment at six months indicated that the Vascular Wrap was safe in this patient population, and there was no difference in safety between the two groups, Angiotech said. The study involved 109 patients at nine clinical centers in Europe as well as the Dutch Antilles. Angiotech is a leader in combining pharma compounds with medical devices and biomaterials.
• Biophan Technologies (West Henrietta, New York) reported results from testing of the company’s technology that will enable MRI within vascular stents, allowing physicians for the first time to assess the health of stented arteries by means of non-invasive MRI technology. Currently, evaluation of restenosis within a stent requires an additional interventional procedure, and both of these procedures require the insertion of a catheter and guidewire into the patient. Biophan’s technology to enable MR imaging within a stent would allow a non-invasive diagnostic procedure to provide similar data, eliminating the need for catheterization of the patient, exposure of the patient to ionizing radiation to obtain the X-ray image, and exposure of the patient to contrast agents. The technology employs the company’s “active” MRI solutions, which it said use proprietary resonant frequency circuitry to enable superior visualization within an MRI.
• Biosense Webster (Diamond Bar, California) reported the launch of the Cartomerge Image Integration Module for diagnosing heart arrhythmias. The Cartomerge enables electrophysiologists to create 3-D electroanatomical maps that are registered with computed tomography (CT) or MRI images. Merging the CT/MRI image with the Carto XP System 3-D map gives electrophysiologists a more precise view of the heart. The Cartomerge Software Module, used with the Biosense Webster Carto XP Electroanatomical Navigation System, allows physicians to accurately locate and map arrhythmias. The Cartomerge module offers electrophysiologists image registration in three steps: importing the CT or MRI image, processing the image on a radiology or Carto XP System workstation, and registering the images. Additional benefits include full DICOM 3 compatibility, minimal point acquisition, new tools for procedure planning and targeting, and improved speed of the system.
• Boston Scientific (Natick, Massachusetts) reported one-year data from its carotid artery stenting (CAS) clinical trial, BEACH. The study evaluates the effectiveness of stenting with embolic protection for patients who are at high-risk for carotid endarterectomy. Results were presented at the 14th annual Peripheral Angioplasty and All That Jazz meeting in New Orleans. The BEACH trial was designed to evaluate Boston Sci’s Carotid Wallstent Monorail Endoprosthesis and the FilterWire EX and EZ Embolic Protection Systems. It is a prospective, non-randomized, single-arm clinical trial that enrolled 747 patients at 47 U.S. sites, with 480 patients in the pivotal phase of the trial. The trial also enrolled 189 patients in a “roll-in” group and 78 patients in a bilateral registry. The trial has a composite primary endpoint of cumulative mortality and morbidity through one year, consisting of stroke, death and myocardial infarction (MI). Christopher White, MD, co-principal investigator of the trial and director of the Ochsner Heart and Vascular Institute and chairman of Ochsner’s department of cardiology, presented data showing a composite one-year endpoint of 9.1%. The breakdown of patients experiencing one or more events is: stroke, 7%; death, 3.2%; and MI, 1.1%. The roll-in group – in which physicians trained on the Boston Scientific devices before entering the pivotal group – reported an event rate of 8.7%. The bilateral group – consisting of patients with carotid artery disease requiring treatment in both carotid arteries – reported an event rate of 7.1%. The BEACH results suggest that CAS may ultimately be a viable treatment option for this high-risk population.
• Cordis (Miami Lakes, Florida), a Johnson & Johnson (New Brunswick, New Jersey) company, said that the FDA has approved a condition of use for the Cypher sirolimus-eluting coronary stent, allowing patients receiving the stent to immediately undergo MRI following implantation. This means patients no longer have to wait two months after a procedure with the Cypher stent before undergoing an MRI, the company said. Approval was granted after laboratory studies demonstrated the Cypher stent is MRI-safe.
• EP MedSystems (West Berlin, New Jersey), a developer of electrophysiology (EP) products used in cardiac rhythm management, reported launch of the Intracardiac Echocardiography-guided Cardioversion to Help Interventional Procedures (CE-CHIP) multi-center trial, the company’s first clinical trial involving intracardiac ultrasound (ICE). The trial is a sequential Phase I and Phase II worldwide clinical trial comparing the cardiac imaging capabilities of ICE during a cardiac catheterization procedure vs. standard transesophageal echocardiography (TEE), a separate standalone procedure in Phase I. In Phase II immediate ICE-guided cardioversion is compared to a conventional cardioversion strategy of greater than three weeks of warfarin therapy in patients with atrial fibrillation (AF). Both phases are designed to reduce need for additional procedures and delays in cardioversion therapy for AF patients.
• Edwards Lifesciences (Irvine, California), has launched the FloTrac sensor in the U.S. The new technology is designed to enable clinicians to more easily monitor patients’ conditions in a critical-care setting. The single-use sensor, which connects to a catheter that is usually already in place in many critically ill patients’ arteries, works in conjunction with the company’s new Vigileo monitor to combine data from the arterial pressure line with other patient parameters to automatically calculate cardiac output on a continuous basis. Of the estimated 13 million critically ill patients in the U.S. who receive an arterial line each year, Edwards estimates that as many as one-third could benefit from the additional hemodynamic monitoring provided by the FloTrac sensor. Until now, the company noted, patients whose conditions required monitoring beyond simple blood pressure measurements, but who were not candidates for more invasive monitoring technologies, were left with few options. “The FloTrac sensor could potentially change the standard of practice in critical care by bringing this level of monitoring to a whole new patient population,” said William McGee, MD, director of ICU quality assurance at Baystate Medical Center (Springfield, Massachusetts).
• IMI International Medical Innovations (Toronto) said patients with elevated skin sterol and a high Framingham global risk score have a significantly higher risk of multivessel disease (narrowing in two or more coronary vessels), according to data presented at the 6th annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology in Washington. The study, which included 649 patients, measured skin sterol non-invasively using the company’s Prevu Point of Care Skin Sterol Test (previously known as Cholesterol 1,2,3). Prevu POC, marketed worldwide by McNeil Consumer Healthcare Canada, does not require the drawing of blood or a special pre-test diet and takes less than five minutes to perform.
• Impulse Dynamics USA (Orangeburg, New York) reported the launch of a Phase II U.S. study of its Optimizer III, a pacemaker-like device being developed for a broad niche targeting restoration of heart function. The first implantation was in a 70-year-old retired construction worker at Saint Joseph’s Hospital (Atlanta), becoming the initial enrollee in the Fix Heart Failure 5 (FIX-HF-5) study sponsored by the U.S. subsidiary of Impulse Dynamics NV (the Netherlands Antilles). The company’s Israeli unit in Tirat Hacarmal is the device developer and manufacturer. The Optimizer III System is an advanced generation of this system, designed to deliver to the heart a specialized form of electrical impulses. The study will enroll about 400 New York Heart Association Class III or Class IV heart failures patients at up to 50 sites. The company already has won CE-marking for the Optimizer II in Europe. The Optimizer system uses a strategy that Impulse Dynamics has titled cardiac contractility modulation (CCM). The company describes CCM therapy as the delivery of “non-excitatory impulses to the heart during a period of time called the absolute refractory period [ARP].” In contrast to the electrical impulses delivered by a pacemaker, CCM impulses do not modify the beating activity of the heart but rather are intended to work on heart cell function. William Abraham, chief of the division of cardiovascular medicine at Ohio State University (Columbus) and co-principal investigator of the study, says that the Optimizer’s primary value is in improving the “contractility” of the heart but without adding to its overall workload. Abraham noted that the Optimizer may actually target a larger market than does resynchronization. Rather than being a type of “no option” therapy, it is most likely to be used for many patients who do not yet require resynchronization but providing them with very similar benefits – that is, not just inhibiting increased deterioration of the heart’s ability to pump but potentially improving it.
• Kensey Nash (Exton, Pennsylvania) reported the final results of the FIRST (First European Investigation Regarding the Systematic use of the TriActiv Device) study, which was designed to examine cost-effectiveness of its TriActiv System in saphenous vein graft patients to support reimbursement for the device in Germany and European countries. The data was presented at the recent German Society of Cardiology meeting in Mannheim, Germany. TriActiv is an embolic protection system used during saphenous vein graft interventions to minimize major complications and is commercialized in both the U.S. and Europe. The FIRST study results showed that the TriActiv system substantially reduced 30-day MACE (major adverse cardiac events) compared to a historical control of patients treated without embolic protection. The reductions in complication rates will be used to generate a cost-effectiveness analysis of the TriActiv system. The FIRST study enrolled 196 patients at 17 sites in Germany.
• Medicure (Winnipeg, Manitoba), a cardiovascular drug discovery company, said that it received a recommendation from an independent data safety monitoring board to continue its Phase II/III MEND-CABG trial. The recommendation is based on the board’s recent review of the safety data in the majority of patients who have completed 30 days of treatment following coronary artery bypass graft (CABG) surgery. The MEND-CABG clinical trial is evaluating the cardioprotective and neuroprotective effects of MC-1 in patients undergoing high-risk CABG surgery. The Phase II portion of the study will enroll up to 900 patients. The primary endpoint of the placebo-controlled, double-blinded study is the reduction in combined incidence of cardiovascular and cerebrovascular death, non-fatal myocardial infarction and non-fatal cerebral infarction, up to and including 30 days following CABG surgery.
• Medtronic (Santa Rosa, California) said that enrollment has begun in its ENDEAVOR IV clinical trial, the final phase of its ENDEAVOR clinical program to be used in support of pre-market approval in the U.S. The first patient implant in the trial was performed by Charles O’Shaughnessy, MD, at EMH Regional Medical Center (Elyria, Ohio). ENDEAVOR IV is a randomized, single-blind trial evaluating the safety and efficacy of the Endeavor drug-eluting coronary stent as compared to the Taxus paclitaxel-eluting coronary stent system from Boston Scientific (Natick, Massachusetts). The ENDEAVOR IV study will include about 1,548 patients randomized one-to-one against the Taxus stent and will be performed at about 80 centers in the U.S. and Canada. The primary endpoint of the trial is target vessel failure at nine months, with a secondary endpoint of major adverse cardiac events at 30 days. The trial includes angiographic and Intravascular Ultrasound follow-up at eight months for a subset of 328 patients.
Separately, Medtronic reported receiving approval from the FDA to add sequential biventricular pacing, known as V-V (ventricle-to-ventricle) timing, to its InSync Sentry and InSync Maximo cardiac resynchronization therapy defibrillators. V-V timing allows physicians to separately adjust the timing of electrical therapy delivered to the heart failure patient’s two ventricles, which can optimize the beating of the heart and enhance the flow of blood throughout the body. Starting in the next two weeks, shipped InSync Sentry and InSync Maximo devices will include V-V timing. The company said it would release special software to allow patients who already have a previous model of these devices to benefit from the feature through a simple, in-clinic software programming change. In addition, the FDA approved a labeling modification for InSync Sentry and InSync Maximo systems to include use for heart failure patients who have prolonged QRS duration.
• Medwave (Danvers, Massachusetts), a developer of sensor-based, non-invasive blood pressure measuring systems, reported that a study titled “A Comparison of The Vasotrac With Invasive Arterial Blood Pressure Monitoring in Children After Pediatric Cardiac Surgery” was published in the May issue of Anesthesia & Analgesia. The researchers concluded that the arterial blood pressure measurements obtained from the Vasotrac system agreed with invasive arterial blood pressure monitoring in children after cardiac surgery and “may be an alternative for obtaining near continuous arterial blood pressure data non-invasively in this pediatric patient population.” Medwave’s Vasotrax Hand Held Monitor, the Vasotrac APM205A NIBP Monitor, the Vasotrac APM205A Model DS, and the MJ23 OEM Module are non-invasive blood pressure monitoring devices.
• MIV Therapeutics (Vancouver, British Columbia) said it received “encouraging” reports from independent researchers evaluating the company’s multi-platform/multi-drug delivery solution in short-term animal studies. The independent porcine studies evaluated the company’s hydroxyapatite (HAp)-based coatings designed for drug-eluting cardiovascular stents and other implantable medical devices. The studies were conducted on stents coated with a combination of HAp and paclitaxel-eluting non-polymeric composite coating. “In summary, stents coated with hydroxyapatite and Paclitaxel have shown uncompromised biocompatibility and safety at 19 days,” said Dr. Greg Kaluza, scientific director of the Cardiovascular Intervention Core at the Methodist Hospital Research Institute, who directed the study. “The low amount of neointima produced by these stents ranks with the performance of the best contemporary bare-metal stents and some drug-eluting stents described in literature utilizing a similar experimental setting. The excellent biocompatibility of the hydroxyapatite coating formulation demonstrated in the earlier study has not been adversely affected by the addition of paclitaxel. This is important because addition of drug to a coating may irreversibly change the overall coating properties and, hence, its biocompatibility.”
• St. Jude Medical (St. Paul, Minnesota) reported FDA approval of its QuickSite 1056T bipolar lead. The lead is used in CRT (cardiac resynchronization therapy) applications for heart failure patients and were launched in the U.S. market in advance of the Heart Rhythm 2005 Scientific Sessions held in early May. QuickSite leads offer a polyurethane-insulated body that transitions to a distal silicone-insulated tip section designed for optimal pushability, torque transfer and tip flexibility; a steerable, S-shaped distal tip designed to improve maneuverability and anchoring of the lead at distal as well as more proximal locations within the coronary sinus; and a choice of either a ball-tipped guiding stylet or a guidewire during the same implant for maximum flexibility in lead placement. The lead also features a radiopaque suture sleeve that enhances visibility on fluoroscopy without blocking visibility of the underlying coils; and a grooved, circumferential tip electrode designed to enhance stability and thresholds. The QuickSite 1056T bipolar lead is designed for use with the St. Jude Medical Epic HF CRT-D the Atlas+ HF CRT-D.
• Thoratec (Pleasanton, California) reported that a Chicago man was the first in the nation to receive the HeartMate II Left Ventricular Assist (LVAS) device in a destination therapy clinical trial. The procedure was performed March 21 by Mark Slaughter, MD, director of the mechanical assist device program at Advocate Christ Medical Center (Oak Lawn, Illinois). The HeartMate II is an implantable, continuous-flow device designed to provide long-term cardiac support for patients who are in late-stage heart failure. The national pivotal trial will determine the safety and efficacy of the device as DT in late-stage heart failure patients and will involve 200 total patients at up to 40 sites, randomizing the HeartMate II to the HeartMate XVE LVAS. Thoratec’s HeartMate XVE is the only commercially available LVAS FDA-approved for DT. In a separate arm of the study, the HeartMate II will be evaluated as a bridge-to-transplant (BTT) for late-stage heart failure patients who are eligible for cardiac transplantation but in need of temporary support until a donor heart becomes available. Up to 25 sites will enroll a total of 133 patients in the BTT arm.
• Toshiba America Medical Systems (Tustin, California) said it demonstrated its 64-slice cardiac computed tomography (CT) performance of the Aquilion 64 CFX at the Cardiovascular Institute of the South (CIS; Houma, Louisiana). CIS is one of the largest heart centers for non-surgical and surgical treatment of both heart and vascular disease in the U.S. “Clearly, the Aquilion 64 CFX image quality and breath-hold of five to 10 seconds has its advantages,” said Peter Fail, MD, director of the cardiac catheterization laboratories and interventional research at CIS. “It has resulted in virtually all studies being of diagnostic quality. Prior to the Aquilion 64 CFX, only about 50% of past cardiovascular CT studies had the temporal resolution required to make a diagnosis.” He added: “Ultimately, the thinner slices and outstanding low-contrast resolution of the Aquilion 64 CFX will improve the sensitivity of plaque characterization algorithms.”
• XDx (South San Francisco, California) has laun- ched a test for the management of heart transplant patients in the hope that it will eliminate the need for potentially dangerous or problem-ridden biopsies, which is the current method of determining if a heart transplant patient is rejecting the donor organ. The test was launched at the International Society for Heart and Lung Transplantation’s (Addison, Texas) annual meeting in Philadelphia, where physicians demonstrated the use of what XDx calls AlloMap molecular expression testing. As such, the company said it is “one of the first practical applications of the human genome project. The current clinical practice for monitoring heart transplant re-jection is endomyocardial biopsy. That procedure requires a small sample of tissue that is clipped from the heart and then analyzed by a pathologist. With AlloMap testing, which received CLIA approval in November 2004, a clinician draws a tube of blood and sends it to the XDx reference lab. The XDx lab begins its processing of the patient’s blood the day it is received, and following quality control procedures the following day, the lab provides a report to the clinician, taking about 48 hours for the whole process. That is the typical amount of time it takes to complete the traditional endomyocardial biopsy. XDx’s test, however, distinguishes rejection vs. lack of rejection, also known as quiescence, by detecting mobilization of the alloimmune response, rather than through graft damage with biopsy.