In what could be seen as a coup, ventricular assist device maker Thoratec (Pleasanton, California) reported last month that the FDA granted it a virtually condition-free approval of its investigational device exemption (IDE) for the company to begin a Phase II pivotal clinical trial for its next generation HeartMate II LVAS (Left Ventricular Assist System). The system is designed to provide long-term cardiac support for patients who are in end-stage heart failure.

The study incorporates a number of unique elements, including the use of the device for both bridge-to-transplantation (BTT) and destination therapy (DT), the first time the FDA has approved a clinical trial with both indications in one protocol, Thoratec said.

The company is in the process of identifying prospective centers beyond those 10 that participated in the Phase I study. Initial patient enrollment could begin within 30 days, pending appropriate approvals within the hospitals, the company said.

A unique aspect of the BTT study design is that the control group will be comprised of data from previous clinical trials and concurrent data from the company's voluntary VAD implant registry, enabling a non-randomized trial design in which all subjects will receive the HeartMate II. The BTT arm of the study will involve 133 patients at up to 25 centers with the primary endpoint being the rate of survival to transplantation, or 180 days.

Secondary endpoints include adverse events, device reliability, quality of life and functional status. The company noted that it has already enrolled 25 patients in the Phase I portion of the BTT trial, leaving 108 patients to be accrued in the Phase II pivotal study.

The DT arm of the study will involve 200 total patients, randomizing the HeartMate II to the currently approved system, the HeartMate XVE on a 2-1 basis, respectively. The study provides for a composite two-year endpoint, which includes patient survival, rate of neurological events and device reliability.

Secondary endpoints in the DT arm of the trial include adverse events, clinical reliability, assessment of neuro-cognitive function and patient quality of life.

Elsewhere in the product pipeline:

Accumetrics (San Diego) President and CEO says there are about 25 million people on an aspirin regimen to prevent platelet aggregation in blood vessels as a way of preventing heart attack or stroke. But that strategy does not always work, particularly in those patients who are aspirin-resistant, a condition that the company said previous studies have shown is associated with triple the risk of heart attack, stroke and death. New studies reported at last month's annual meeting of the American College of Cardiology (ACC; Bethesda, Maryland) in Orlando confirm that up to 27% of aspirin users with coronary artery disease are resistant to aspirin's antiplatelet effects. Furthermore, the research indicated that resistance to aspirin and clopidogrel, known by the brand name Plavix, may occur together. So how does a doctor know that a patient is going to be aspirin-resistant before relying on that all-purpose over-the-counter drug to prevent further cardiovascular problems? Accumetrix thinks it has the answer in the VerifyNow Aspirin Test, for which the company received a CLIA waiver last month for a "new, improved version" of the test. The test was initially approved by the FDA in 2003. However, that test required up to an hour and a half before results were available. With the VerifyNow Aspirin test, the company has whittled the time it takes to get results down to about 10 minutes.

AngioScore (Alameda, California), a developer of angioplasty tools for interventional cardiologists and radiologists, reported the completion of the U.S. clinical trial for its flagship AngioSculpt Scoring Balloon Catheter in coronary lesions and the conclusion of follow up on the 200 patients in the trial. The multicenter clinical trial is a prospective clinical study of the safety and efficacy of the AngioSculpt scoring balloon catheter in 200 patients undergoing angioplasty to treat coronary artery disease. The study examines acute outcomes when the AngioSculpt scoring balloon catheter is used for the treatment of a hemodynamically significant coronary artery stenosis, including in-stent restenosis, for the purpose of improving myocardial perfusion. Principal Investigator Martin Leon, MD, associate director of Cardiovascular Interventional Therapy at Columbia University Medical Center and chairman of the Cardiology Research Foundation, said: "The AngioSculpt Scoring Balloon Catheter is a promising new approach to dilatation of challenging lesions and potentially a valuable adjunct to drug-eluting stents, facilitating precise stent placement and complete expansion."

Biosite (San Diego) said the FDA has accepted the company's Triage Stroke Panel premarket approval application (PMA) for further review. The panel is intended for use as an aid in the assessment and diagnosis of cerebral ischemia, or stroke. The Triage Stroke Panel consists of multiple biomarkers and uses a proprietary algorithm to calculate a single MultiMarker Index result. Biosite submitted its PMA for the Triage Stroke Panel in December. Existing methods to diagnose stroke and confirm symptoms utilize radiographic imaging, such as computed tomography, which are subject to interpretation and often unable to detect the most common form of stroke until 12 to 24 hours after an event. Currently in the U.S., there is no rapid, in vitro diagnostic test using protein markers from a blood sample commercially available for use as an aid in the diagnosis of stroke.

Dade Behring Holdings (Deerfield, Illinois) said that its NT-proBNP (N-terminal pro brain natriuretic peptide) test has received FDA clearance for use on its Stratus CS Acute Care Diagnostics System. The assay has been cleared to aid in the diagnosis of heart failure, including assessment of heart failure severity in patients diagnosed with congestive heart failure, and risk stratification of patients with acute coronary syndrome and heart failure. The test will begin shipping later this month. In December 2004, clearance was received for the use of NT-proBNP in the assessment of heart failure severity and risk stratification on the company's Dimension instruments with Heterogeneous Immunoassay Module.

diaDexus (South San Francisco, California) is going for a second use for its PLAC test, which is now used to predict the risk of coronary heart disease in chronic patients. The company recently submitted a 510(k) premarket notification to the FDA seeking marketing clearance for the PLAC test as a diagnostic test to help predict the risk of stroke. The PLAC test is a blood test that measures an enzyme in the blood called lipoprotein-associated phopholipase A2 (Lp-PLA2). The company said that "large population studies" demonstrated that elevated Lp-PLA2 is associated with an increased risk of ischemic stroke. Mohan Iyer, vice president of business development for diaDexus, said that the company hopes to get marketing clearance from the FDA by mid-year or earlier. "This is not an entirely new submission," Iyer said. "It's ... based on the coronary heart disease submission to a large extent, and our hope is that many of the questions that the FDA might ask have already been cleared in the original submission." diaDexus secured approval of its PLAC test in coronary heart disease in July 2003. It was the company's first FDA-approved product.

Genzyme (Cambridge, Massachusetts) said the first patient has been treated in a new Phase II clinical trial examining the safety and effectiveness of locally delivered gene transfer for patients with peripheral arterial disease (PAD). Genzyme's experimental therapy, using Ad2/HIF-1 alpha, an engineered form of the HIF-1 alpha gene, is designed to promote the growth of new blood vessels and improve circulation in patients' limbs. The randomized, placebo-controlled study will take place at up to 35 medical centers in the U.S. and Europe. It will enroll up to 300 patients diagnosed with severe intermittent claudication, a type of PAD that results in disabling pain or fatigue in the legs, brought on by exercise. Plans are to enroll 75 patients each into one of three dosing groups or a placebo arm. In addition to safety, the trial will evaluate the effectiveness of each dose in several measures of efficacy.

Kensey Nash (Exton, Pennsylvania) said it has received CE mark approval for a new triActiv FX System. The company is preparing to launch the product, designed to prevent heart attacks during the interventional treatment of saphenous vein grafts in patients who previously received coronary bypass surgery but now have blockages in the grafts, through direct sales and distributors in Europe. The triActiv FX System features design enhancements to the triActiv System platform, including a new balloon inflator that simplifies catheter exchanges during the procedure and a monorail flush catheter to enhance usage and reduce procedure time. A multi-center, non-randomized clinical study, to support regulatory clearance of the triActiv FX System in the U.S., will begin later this month, Kensey Nash said.

Medtronic (Minneapolis) reported the European introductions of the EnRhythm dual-chamber pacemaker and EnTrust implantable cardioverter-defibrillators (ICDs) in single- and dual-chamber versions. The company received the CE mark for the devices on Feb. 4. Medtronic said the products incorporate several features that provide important patient benefits, including an innovative pacing mode called Managed Ventricular Pacing, or MVP, available in the dual-chamber EnRhythm and EnTrust devices. The EnRhythm device is the first pacemaker to include MVP, which Medtronic first introduced in its Intrinsic ICD last year. The company said MVP promotes natural heart activity by "significantly reducing" unnecessary pacing in the heart's lower right chamber and automatically switching to pace the upper right chamber when normal heart conduction is present. With the MVP mode, automatic switching between dual-chamber pacing and single-chamber atrial pacing can reduce the amount of ventricular pacing to less than 5%, compared to 50% or more with typical dual-chamber pacing, according to Medtronic. The company said a key feature of the EnTrust devices is its exclusive ATP During Charging, an advancement of anti-tachycardia pacing (ATP). ATP uses pacing pulses to painlessly terminate fast, dangerous heart rhythms originating in the ventricle. ATP During Charging enables the use of ATP while the EnTrust capacitor charges to prepare for the possible delivery of a high-energy shock if needed. The EnRhythm pacemaker and EnTrust ICDs also offer Reactive ATP, a feature enabling the devices to continually search for opportunities to restore a patient's normal sinus rhythm during long, fast heart rhythm episodes in the atrium. Additionally, enhanced diagnostics in these devices provide comprehensive information to assist physicians in the diagnosis of additional types of heart rhythm problems, especially in the atrium.

Medtronic Vascular (Santa Rosa, California) said it has obtained CE mark approval on its Valiant Thoracic Stent Graft with Xcelerant Delivery System for commercial release in Europe. Valiant is a next-generation stent graft built on the company's thoracic endovascular clinical history, which includes more than 16,000 implanted grafts. The Valiant system is more conformable than earlier-generation devices and the new delivery system enables precise transluminal deployment of the stent graft. It also offers more size and end configuration options. The Valiant thoracic system also will offer covered graft lengths of up to 20 centimeters for maximum lesion coverage and the use of fewer graft segments to complete procedures. Medtronic Vascular said its commercialization of the Valiant system outside the U.S. would be phased in over the spring and summer.

Neoprobe (Dublin, Ohio), a developer of oncology and cardiovascular surgical and diagnostic products, said it has received notification that its 510(k) application for the revised and enhanced Quantix/OR blood flow measurement has been accepted by the FDA for review. In addition, Neoprobe said it has completed the necessary regulatory steps to begin marketing the product in the European Union. The company reintroduced the Quantix/OR at a joint meeting of the German, Austrian and Swiss cardiovascular surgical society meeting in Hamburg, Germany, last weekend. The Quantix/OR has been revised to enhance visual ergonomics and to facilitate surgeon use. The flexible probe configuration will permit surgeons to access vessels for measurement during both on- and off-pump by-pass procedures. The company said it is planning full product re-introduction at this month's American Association for Thoracic Surgery meeting.

St. Jude Medical (St. Paul, Minnesota) reported enrollment of the first patients last month in the ASSERT (ASymptomatic AF and Stroke Evaluation in Pacemaker Patients and the AF Reduction Atrial Pacing Trial) clinical study. The study will follow 2,500 patients for 3-1/2 years to determine if pacemaker-detected AHRE (Atrial High Rate Events) predict an increased risk of stroke in elderly hypertensive patients without previous atrial fibrillation (AF). ASSERT also examines the efficacy of St. Jude Medical's AF Suppression algorithm in helping these patients avoid symptomatic AF. Sinan Gursoy, MD, enrolled the first U.S. patient in the ASSERT study at Naples Community Hospital (Naples, Florida) and Seong-Wook Han, MD, enrolled the first Asian patient at the Keimyung University Dongsan Medical Center (Daegu, South Korea). The study is being conducted at 125 international clinical centers and coordinated by the Population Health Institute at McMaster University (Hamilton, Ontario). Patients enrolled in the study must be over 65, have a history of hypertension requiring drug therapy, and be recently implanted with a St. Jude Medical Identity ADx DR pacemaker with the AF Suppression algorithm.