CDU
Two years after a 70-year-old retired construction worker became the first enrollee in the Fix Heart Failure 5 (FIX-HF-5) study by being implanted with the Optimizer III device from Impulse Dynamics (Orangeburg, New York), the company last month reported completion of patient enrollment in the trial. The first patient was implanted with the device at St. Joseph’s Hospital (Atlanta) in April 2005.
The FIX-HF-5 study is the company’s largest randomized clinical trial to date and is intended to evaluate the safety and efficacy of the Optimizer — CE-marked and an investigational device in the U.S. — designed to deliver cardiac contractility modulation (CCM) non-excitatory impulses to treat patients with moderate to severe heart failure.
The system consists of a pacemaker-like device and conventional pacing leads which are designed to sense electrical activity and deliver CCM therapy to the cardiac tissue. The device is implanted much like a pacemaker procedure, but compared to conventional pacing methods, the system uses the company’s CCM therapy in which electrical impulses are delivered to the heart after the heart has already initiated its contraction. And unlike conventional pacing signals, CCM is intended to increase the forcefulness of the heart’s pumping action rather than initiating a new contraction.
Daniel Burkhoff, MD, PhD, corporate VP and chief medical officer at Impulse Dynamics told Cardiovascular Device Update that the FIX-HF-5 trial enrolled its last patient at the end of May, so the company has about a year of follow-up left before the study is complete.
“We’ll be focusing a lot of effort in ensuring the quality of data and data monitoring,” Burkhoff said. After that is completed, Burkhoff said, the company will spend three to four months analyzing the data and then submit it to the FDA for approval.
Thus, it would be at least one year and nine months before the company is sitting in a panel meeting for the device. Still, company officials emphasized that the enrollment of the last patient in the study is an important milestone.
Burkhoff said the study focused on patients who have been taking all the approved drugs to treat heart failure, but are still having symptoms of Class III or Class IV heart failure and who are not currently eligible for any other therapies. He said the trial excluded patients who have an indication for cardiac resynchronization therapy (CRT).
“In contrast to other device-based therapies for heart failure, such as [CRT], this study is focused on those patients without evidence of ventricular dyssynchrony. Patients with symptomatic heart failure without dyssynchrony currently have few treatment options,” said Yuval Mika, MD, COO of Impulse.
The company says that its technology stems from a scientific discovery regarding the electrical control of tissue function.
More than 50 investigational sites across the U.S. enrolled more than 760 patients and randomized nearly 430 patients in a two-year period.
“We have been very active in this trial and are committed to offering our patients the newest treatment options available,” said Steven Krueger, MD, director of the Heart Improvement Program, Bryan LGH Heart Institute (Lincoln, Nebraska) and a lead FIX-HF-5 enroller. “We believe that CCM therapy has an effect on the cellular level. This is a novel approach with the potential to help many patients without alternative treatments.”
According to the company, functional assessments made at baseline and throughout the follow-up period include cardiopulmonary treadmill exercise testing, six-minute walk test, NYHA classification, and quality-of-life scoring. An independent Data and Safety Monitoring Board are also monitoring safety variables such as the rate and cause of hospitalizations and deaths, the company noted.
“The Optimizer System with CCM Therapy is an exciting approach with the potential to treat those patients with Class III or Class IV heart failure, despite treatment with standard drug therapies, who presently have no other options,” said William Abraham, MD, chief of the Division of Cardiovascular Medicine, at The Ohio State University (Columbus) and FIX-HF-5 co-principal investigator. “The primary value here lies in the fact that the device is intended to improve the strength of the heart beat without adding to its overall workload. The combination of improved strength and increased efficiency of the heart makes us very optimistic about this particular therapy.”
The device received a boost last September with the report of positive clinical trial data at the 10th annual scientific meeting of the Heart Failure Society of America’s (HFSA; St. Paul, Minnesota) in Seattle. Those results, however, involved a separate European trial evaluating CCM called FIX-4. The FIX-4 data indicated that the Optimizer enhances exercise tolerance and improves quality-of-life.
Alan Kadish, MD, a professor in the Division of Cardiology at Northwestern University (Chicago) and FIX-HF-5 co- principal investigator, said, “Unlike other cardiac devices for heart failure like pacemakers and defibrillators, the Optimizer System is designed to modulate the strength of contraction of the heart muscle rather than its rhythm. It is always important to consider and evaluate new heart failure therapies in order to do everything possible to potentially improve the lives of patients with this debilitating disease.”
Impulse estimates that the U.S. healthcare system will spend more than $20 billion in related costs for the treatment of heart failure patients in 2007.
Elsewhere in the product pipeline:
• Boston Scientific (Natick, Massachusetts) reported 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. The FDA approved the Nex-Stent and FilterWire EZ for use in patients with carotid artery disease 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. The FilterWire EZ Embolic Protection System is designed to efficiently capture plaque and other material that may dislodge during stent implantation, thereby reducing the risk of procedural-related stroke or heart attack.
• CardioTech International (Wilmington, Massachusetts), a developer of advanced materials and medical devices for the treatment of cardiovascular and other diseases, filed for a U.S. patent on its antimicrobial formulation of ChronoFlex medical grade polymer and its method of fabrication. It said that these materials are designed to provide a new method to better control foreign body-derived infections without the use of antibiotic drugs. Cardiotech’s antimicrobials can be used in devices as a polymer or a coating. Andrew Reed, PhD, CardioTech’s VP of Science and Technology, said, “Current technology in the marketplace uses antibiotic drugs, which often become depleted in the body and can form antibiotic-resistant bacteria. Moreover, the antimicrobial component of these polymers has been designed to be non-leaching as a result of the polymerization process. Remaining as a component of the polymer is a vital factor for preventing infection.” CardioTech makes products and materials for the treatment of cardiovascular, orthopedic, oncology, urology and other diseases.
• CoAxia (Maple Grove, Minnesota) reported the enrollment of the first two patients in its Flo 24 safety and feasibility study of its NeuroFlo Perfusion Augmentation Therapy for ischemic stroke patients who show up for treatment as late as 24 hours after stroke onset. CoAxia said it believes NeuroFlo is the first intervention evaluated which attempts to improve blood flow to the brain this late after a stroke. The NeuroFlo treatment is intended to deliver blood to the affected area of the brain by providing an increase in blood flow via alternative, collateral pathways around the blocked artery. The device, a dual-balloon catheter, is placed in the descending aorta and works by restricting flow in the descending aorta and thus increasing blood flow to the brain, according to CoAxia. The Flo 24 trial will enroll 25 patients, and the first two patients in the trial “seem to have done well” and “seem to have benefited” from the treatment, according to the company. The company said Flo 24 complements its ongoing SENTIS pivotal study, which is evaluating the NeuroFlo treatment in patients up to 10 hours after the onset of their symptoms. The SENTIS trial has now enrolled more than 65 patients at more than 20 major medical centers, the company noted. Within minutes of an occlusion of a cerebral artery, brain cells begin to die, creating a non-salvageable region called the infarct core. Most strokes also involve a region of brain tissue, which is lacking sufficient oxygen for long-term survival, but can be saved if blood flow is restored or augmented, CoAxia said. This region, called the penumbra, is the target for all acute stroke treatments. CoAxia considers its technology to be a potential alternative or complement to clot-focused techniques like pTA. Already somewhat active following an ischemic stroke, collateral pathways are capable of further increasing the delivery of oxygenated blood to the stroke’s ischemic penumbra. The ability to salvage that penumbra and minimize the eventual size of the infarct may lead to improved neurological recovery, the company said. CoAxia is focused on providing perfusion augmentation therapies that improve outcomes for patients with cerebral ischemia resulting from stroke, vasospasm and other conditions.
• Cordis Endovascular (Baltimore), a division of Cordis (Miami Lakes, Florida), reported worldwide launch of its Aviator Plus balloon dilatation catheter for use in angioplasty procedures for patients with carotid and or renal artery blockages. Aviator combines a high-pressure expansion and low-profile .014-inch rapid exchange or single operator system that facilitates procedural speed and efficiency by enabling fast inflation and deflation times. Fast inflation and deflation time during carotid or renal intervention procedures helps to limit the period of distal ischemia, and the low profile may help reduce the risk of plaque disruption and embolization when crossing the lesion. Aviator features include a sleek (<.90mm) manicured tip, 3.3 french shaft, and modified Duralyn balloon material on a 4 french system. It is available in 4mm-7mm diameters and 1.5cm-4cm lengths on 142cm shafts. Cordis Endovascular makes technologies for the treatment of peripheral vascular disease.
• CryoCath Technologies (Montreal) said that data on the company’s Arctic Front catheter system to treat atrial fibrillation (AF) was presented at the European Society of Cardiology (Europace) Conference in Lisbon, Portugal. Arctic Front is a minimally invasive cryo-balloon catheter designed specifically to treat AF. This bi-directional, double balloon catheter enables physicians to rapidly isolate all four pulmonary veins for the treatment of AF. Approved in Europe, it has treated more than 750 patients in more than 24 centers. CryoCath specializes in cryotherapy products to treat cardiovascular disease.
• diaDexus (South San Francisco, California) reported that the U.S. Patent and Trademark Office issued it a patent covering methods of diagnosing an individual’s susceptibility for developing atherosclerotic disease, including myocardial infarction and stroke, by analyzing a blood sample for lipoprotein-associated phospholipase A2 (Lp-PLA2) enzymatic activity. Lp-PLA2 an enzyme implicated in the formation of vulnerable, rupture-prone plaque, was discovered by scientists at GlaxoSmithKline (GSK; Research Triangle Park, North Carolina). The patent is one of a group of Lp-PLA2-related GSK patents for which diaDexus has an exclusive diagnostic license. diaDexus sells the PLAC test, an Lp-PLA2 immunoassay, for use as an aid in assessing risk of stroke or heart attack. The PLAC test is a blood test that measures a new risk factor for heart disease and stroke-Lp-PLA2, a cardiovascular-specific inflammatory marker implicated in the formation of vulnerable, rupture-prone plaque. The PLAC test is cleared for marketing by the FDA as an aid in determining risk for coronary heart disease and ischemic stroke associated with atherosclerosis.
• Endovalve (San Francisco) reported 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,” Endovalve president/CEO Robert Wilkins told attendees at the Medtech Insight Investment In Innovation Medical Device Summit. Endovalve makes percutaneous valve-replacement systems to treat mitral regurgitation.
• ev3 (Plymouth, Minnesota) is conducting the DURABILITY II trial of its Protégé Ever Flex Self-Expanding Stent System under a conditional Investigational Device Exemption (IDE) from the FDA with the goal of expanding the product’s U.S. indication to include treatment of peripheral artery disease (PAD). The EverFlex was designed for use in the superficial femoral artery (SAF), where PAD is often present. The trial 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, according to ev3. The study will include 30 clinical trial sites across the U.S. Jim Corbett, CEO of ev3, told CDU that the management of PAD patients is challenging because of “inadequate scientific data to definitively help clinicians make the right decisions on these types of lesions.” The company banners durability as one of the product’s key differentiating features, noting that its “three weave-peaks allow stress to be distributed through more stent material” and that its “multi-step manufacturing process and careful attention to detail produces an optimal stent finish” enabling it to achieve “superior durability.” It said DURABILITY II will be the first trial in the treatment of PAD to explore single-stent treatment of lesions as long as 16 centimeters and will include rigorous, five-year follow-up on stent fracture, ev3 said. Supported by the FDA, the design facilitates a single-arm study of bare nitinol stents in the superficial femoral and popliteal arteries.
• LeMaitre Vascular (Burlington, Massachusetts) reported the first implant in the UNITE clinical trial of its UniFit abdominal stent graft. The study will evaluate the safety and effectiveness of the company’s UniFit abdominal stent graft in the treatment of aorto, aorto-iliac, and/or iliac aneurysms. The primary effectiveness endpoint of the study is based on aneurysm exclusion as evaluated through one- year follow-up. The UNITE study compares the safety and efficacy of the UniFit against open surgical abdominal aorta repair, because there are currently no aorto-uni-iliac endovascular stent grafts indicated for this use. The UniFit is a single-bodied aorto-uni-iliac stent graft used to treat an aortic aneurysm through a minimally invasive endovascular procedure. The device’s encapsulated design minimizes the extent to which its stents contact the blood stream or the vessel wall. This design also allows a wider range of stent graft sizes, including tapered and custom grafts, to fit a wider range of patient anatomies than many competing products. LeMaitre makes devices for the treatment of peripheral vascular disease.
• Positive 12-month study results for the VALOR clinical study evaluating the Talent thoracic stent graft system, were presented during the annual meeting of the Society for Vascular Surgery in Baltimore. Sponsored by Medtronic (Minneapolis), VALOR is a test group patients with thoracic aortic aneurysms who were considered candidates for open surgical repair. The primary endpoint is “all cause” mortality at 12 months, comparing minimally invasive endovascular stent graft treatment to a historical surgical control group. The Talent system demonstrated 100% patency, which is a measure of the graft’s ability to resist collapse and remain open for proper blood flow, and there was a 99.5% success rate in deploying the stent graft. Also, the stent graft system used in the study was available in diameters ranging from 22 mm to 46 mm. Without this wide range of sizes, approximately 25% of the test arm patients in the VALOR trial would not have had the minimally-invasive stent graft therapy available to them as a treatment alternative.
• SynCardia Systems (Tucson, Arizona) reported the availability for clinical investigation of a portable driver, the Companion, designed to allow stable U.S. patients to recover at home while they wait for their donor heart for transplant. For operating room and intensive care unit applications, the Companion is designed to be docked into a hospital cart that features a 15” monitor intended to be viewed from across a room. For stable patients to be discharged, Companion is designed to be “re-docked” into a smaller caddy that features large wheels and an adjustable handle intended to facilitate patient mobility. SynCardia makes the only FDA- and CE mark-approved temporary total artificial heart.
• Synthetic Blood International (Costa Mesa, California) reported positive data from a statistical analysis of its Phase IIa study with Oxycyte in patients with traumatic brain injury. In line with preliminary study results the company reported in December, the company said statistical results confirmed that the primary endpoint of increasing patients’ oxygen tension levels compared with baseline was met. Data also show a decrease in patient glucose and lactate/pyruvate (LP) ratio, consistent with increased glucose metabolism. Patients in the trial were stabilized with either 50% or 100% oxygen. Data determined that results of both treatment arms were favorable, with statistically significant differences in some data between the two treatment arms, according to Synthetic Blood.