Medtronic to Acquire Invatec; Invatec Marks Product Milestones
January 25, 2010—Medtronic, Inc. (Minneapolis, MN) announced that it has signed a definitive agreement to acquire Invatec (Roncadelle, Italy), a developer of medical technologies for the interventional treatment of cardiovascular disease, and two affiliated companies: Fogazzi (Brescia, Italy), which provides polymer technology to Invatec, and Krauth CardioVascular (Hamburg, Germany), which distributes Invatec products in Germany. The agreement calls for Medtronic to make an initial payment of $350 million to Invatec and additional payments of up to $150 million for Invatec’s achievement of specific milestones.
According to Medtronic, Invatec’s product line of stents, angioplasty balloons, and accessory products complement therapies and products in Medtronic’s CardioVascular business. The acquisition of Invatec adds a peripheral franchise and pipeline to Medtronic and enhances its coronary product offering. Invatec has brought four drug-eluting balloons to market (outside the United States), covering the coronaries and lower extremity vessels. It develops lesion-specific solutions, including therapies for below-the-knee and carotid artery disease, Medtronic stated.
On January 19, Invatec announced that it received 510(k) clearance from the US Food and Drug Administration to market the Reef HP percutaneous transluminal angioplasty (PTA) balloon catheter for use in peripheral high-pressure dilatation procedures. The company stated that the lesion-specific design of the balloon material is particularly useful in patients with a range of peripheral lesions, such as dialysis patients, whose arteriovenous shunts often create fibrous and hard-to-dilate lesions. The Reef HP balloon is made from Invatec’s Flexitec XF material, with a working pressure range of up to 22 atm, a low compliant balloon, and low-profile design. In the United States, the balloon is available in diameters of 4 to 8 mm and lengths of 20 to 80 mm, Invatec advised.
"We often encounter calcified and resistant lesions in peripheral vessels and in hemodialysis access interventions," commented Robert L. Vogelzang, MD. "Invatec’s addition of a high-pressure PTA balloon will aid in the successful treatment of these challenging lesions."
On January 27, Invatec announced the European launch of the Maris Plus self-expanding peripheral stent system in new 6-, 7-, and 8-mm diameters, appropriate for interventions involving the superficial femoral arteries. The 9-, 10-, and 12-mm diameters of the stent are already marketed for the iliac arteries. At the stent ends, the device’s cell design allows interventionists to place several stents in series without stiffening the artery in the overlap region. The stent geometry creates an overlap region that allows two stents to act like one in the femoral artery and provides flexibility, fracture resistance, and tailored deployment, the company stated.
On January 29, Invatec announced that the first clinical results for the use of the In.Pact Amphirion paclitaxel-eluting balloon for complex critical limb ischemia (CLI) in below-the-knee vessels were presented at the LINC 2010: Leipzig Interventional Course meeting in Leipzig, Germany. Investigator Andrej Schmidt, MD, reported that preliminary results indicate a dramatic reduction in the restenosis rate with application of the device.
Dr. Schmidt commented, "In our experience, 69% of CLI patients with long lesions show restenosis after 3 months. The In.Pact Amphirion was able to bring this number down to 31%. Considering the mean lesion lengths of 17 cm and 58% rate of total occlusions before intervention, these results have the potential to change the way we treat complex CLI."
Professor Dierk Scheinert, MD, principal investigator of the In.Pact Amphirion registry, added, "It took us several years to develop adequate techniques to successfully reopen below-the-knee arteries, but we had no means of preventing restenosis for longer arterial segments. Drug-eluting stents are only feasible in short lesions. The drug-eluting balloon is the first method that brings down restenosis rates in those complex CLI cases. An interesting observation is also the nature of the restenosis, if it appears after treatment with the drug-eluting balloon, we see focal segments, not renarrowing along the total artery. This makes reintervention less complex."
Invatec plans to proceed with its clinical trial program to provide further definitive proof that drug-eluting balloons can benefit patients with arterial disease in the coronaries, in hemodialysis shunts, and throughout the entire leg. The company has initiated several clinical trials to assess its In.Pact paclitaxel-eluting balloon line, which includes four different balloon platforms. Previous trials conducted on the superficial femoral artery and coronary arteries have shown outcomes favoring drug-eluting balloons, the company stated.
Access Scientific’s PICC Wand Receives FDA Clearance
January 27, 2010—Access Scientific, Inc. (San Diego, CA) announced that it has received clearance from the US Food and Drug Administration for the PICC Wand, which enables clinicians to insert a peelable sheath for peripherally inserted central catheter (PICC) or midline catheter placement using the accelerated Seldinger technique. The PICC Wand is designed to be used primarily by vascular nurse specialists for insertion of PICCs.
According to the company, the PICC Wand’s unitary design combines all components of the older, modified Seldinger technique (the needle, guidewire, dilator, and sheath) into one device that also protects against accidental needlesticks. Its "Fast-flash" feature provides early detection of vessel entry.
The device’s safety introducer with peelable sheath is designed to reduce the risk of accidental needlesticks, bleeding, contamination, guidewire embolism, and loss of cannulation. Air embolism is among the patient risks of modified Seldinger technique that are reduced by the Wand and its accelerated Seldinger technique. Beginning in October 2008, the Centers for Medicare & Medicaid Services ceased reimbursing health care institutions for air embolism, which the agency considers preventable. The average cost to treat this complication, which can be fatal, is estimated at $66,000 per case, the company noted.
DUET Will Study Ekos’ Ultrasound-Accelerated Thrombolysis
January 18, 2010—Ekos Corporation (Bothell, WA) acknowledged the beginning of the physician-sponsored DUET study. DUET is a Dutch multicenter randomized trial designed to compare ultrasound-accelerated, catheter-directed thrombolysis to standard catheter-directed thrombolysis in patients with recently thrombosed infrainguinal native arteries or bypass grafts. The study’s hypothesis is that ultrasound-accelerated thrombolysis with the Ekos device will significantly reduce therapy time (by at least 12 hours) compared to standard thrombolysis alone without increasing the complication rate.
The DUET study’s principal investigator is Jean-Paul deVries, MD, of St. Antonius Hospital Niewegein in The Netherlands.
According to Dr. deVries, a total of 60 adult patients with recently (between 1 and 7 weeks) thrombosed infrainguinal native arteries or bypass grafts with acute limb ischemia Rutherford class I and IIa will be randomly allocated to either group A (standard thrombolysis) or group B (Ekos ultrasound-accelerated thrombolysis). The anticipated duration of recruitment will be 1 year. The primary endpoint is the duration of catheter-directed thrombolysis needed for uninterrupted flow in the thrombosed infrainguinal native artery or bypass graft with outflow via at least one crural artery.
"Current therapy can take a significant amount of time during which the patient is restricted to a bed in a hospital monitoring unit, and bleeding complications increase with duration of thrombolysis," commented Dr. deVries. "This new ultrasound-accelerated technology promises to significantly reduce the treatment time. Such a reduction, if proven, could reduce treatment costs, patient discomfort, and the risk of bleeding, which is sometimes associated with these types of drugs."
Meta-Analysis of Studies Supports Ultrasound-Enhanced Thrombolysis
January 25, 2010—In Stroke, Georgios Tsivgoulis, MD, et al published a review of the safety and efficacy data for ultrasound-enhanced thrombolysis (2010;41:280-287).
According to the investigators, ultrasound-enhanced thrombolysis is a promising new approach to facilitate reperfusion therapies for acute ischemic stroke. So far, three different ultrasound technologies were used to increase the thrombolytic activity of tissue plasminogen activator (tPA), including transcranial Doppler (TCD), transcranial color-coded duplex (TCCD), and low-frequency ultrasound. In this study, the investigators performed a meta-analysis to evaluate the safety and efficacy of ultrasound-enhanced thrombolysis compared to the current standard of care, intravenous tPA.
From their findings, the investigators concluded that the present safety and signal-of-efficacy data of high-frequency, ultrasound-enhanced thrombolysis should be taken into account in the design of future randomized controlled trials.
As detailed in Stroke, the investigators used Medline, Embase, and Cochrane database searches to identify and abstract all studies of ultrasound-enhanced thrombolysis in acute cerebral ischemia. Principal investigators of those studies were contacted if data not available through peer-reviewed publication were needed. Symptomatic intracerebral hemorrhage and recanalization rates were compared between tPA, tPA + TCD ± microspheres (µS), tPA + TCCD ± µS, and tPA + low-frequency ultrasound.
The investigators reported that a total of six randomized (n = 224) and three nonrandomized (n = 192) studies were identified. The rates of symptomatic intracerebral hemorrhage in randomized studies were as follows: tPA + TCD, 3.8% (95% confidence interval [CI], 0%–11.2%); tPA + TCCD, 11.1% (95% CI, 0%–28.9%); tPA + low-frequency ultrasound, 35.7% (95% CI, 16.2%–61.4%); and tPA alone, 2.9% (95% CI, 0%–8.4%). Complete recanalization rates were higher in patients receiving a combination of TCD with tPA 37.2% (95% CI, 26.5– 47.9%) compared with patients treated with tPA alone 17.2% (95% CI, 9.5%–24.9%).
In eight trials of high-frequency (TCD/TCCD), ultrasound-enhanced thrombolysis, tPA + TCD/TCCD ± µS was associated with a higher likelihood of complete recanalization (pooled odds ratio, 2.99; 95% CI, 1.7–5.25; P = .0001) when compared to tPA alone. High-frequency, ultrasound-enhanced thrombolysis was not associated with an increased risk of symptomatic intracerebral hemorrhage (pooled odds ratio, 1.26; 95% CI, 0.44–3.6; P = .67).
Study Analyzes Effect of Aging on Deformations of the SFA Caused by Flexion
January 25, 2010—Christopher P. Cheng, PhD, et al published findings from a study that sought to describe geometric changes of the superficial femoral artery (SFA) resulting from hip and knee flexion in older patients. The investigators noted that vessel deformations have been implicated in endoluminal device fractures, and therefore, better understanding of these deformations could be valuable for device regulation, evaluation, and design. The study was published in the Journal of Vascular and Interventional Radiology (2010;21:195-202).
As detailed by the investigators, the SFAs of seven healthy patients aged 50 to 70 years were imaged with magnetic resonance angiography with the legs straight and with hip and knee flexion. Axial, twisting, and bending deformations were quantified from geometric models constructed from these images.
The investigators found that there was greater shortening in the bottom third of the SFA than in the top two-thirds (top, 5.9% ± 3%; middle, 6.7% ± 2.1%; bottom, 8.1% ± 2% [mean ± SD]; P < .05), significant twist in all sections (top, 1.3 ± 0.8°/cm; middle, 1.8 ± 1.1°/cm; bottom, 2.1 ± 1.3°/cm), and a greater curvature increase in the bottom third than in the top two-thirds (top, 0.15 ± 0.06 cm-1; middle, 0.09 ± 0.07 cm-1; bottom, 0.41 ± 0.22 cm-1; P < .001).
The investigators observed that the SFA tends to deform more in the bottom third than in the other sections, likely because of less musculoskeletal constraint distal to the adductor canal and vicinity of knee flexion. The SFAs of these older subjects curve off axis with normal joint flexion, probably resulting from known loss of arterial elasticity with age. This slackening of the vessel enables a method for noninvasive quantification of in vivo SFA strain, which may be valuable for treatment planning and device design. In addition, the spatially resolved arterial deformations quantified in this study may be useful for commercial and regulatory device evaluation, the investigators concluded.
Analysis of MAVERIC Studies Supports Medtronic’s Exponent CAS System
January 25, 2010—In Stroke, (Randall T. Higashida, MD, et al published findings from a combined analysis of the MAVERIC (Medtronic AVE Self-Expanding Carotid Stent System With Distal Protection) I and II trials to evaluate the safety and feasibility of this system among patients at high risk for surgical endarterectomy (2010;41:e102-e109).
According to the investigators, 498 patients were enrolled in the MAVERIC I (99 patients) and MAVERIC II (399 patients) studies from June 2001 to October 2004. The results were pooled for statistical analysis of a common primary endpoint, which was the 365-day rate of major adverse events. Clinical follow-up was done at 30 days, 6 months, and 365 days postprocedure.
The investigators reported in Stroke that the 365-day major adverse event rate was 12.5% (defined as death, stroke, or myocardial infarction within 30 days and death, ipsilateral stroke, or myocardial infarction from days 31 to 365). The incidence of neurological death through 365 days was 1.1%. The 30-day major adverse event rate was 5.4%. Subgroup analyses showed no notable differences in the 365-day major adverse event rate for symptomatic patients compared with asymptomatic patients.
The data demonstrate that treatment of carotid artery disease with carotid artery stenting with a self-expanding stent and distal embolic protection results in a low 30-day adverse event rate, including the occurrence of stroke in patients at high risk for carotid endarterectomy, the investigators concluded.
Data Presented on Cook's REFORM Trial at ISET
January 19, 2010—Cook Medical (Bloomington, IN) announced that findings from the REFORM clinical trial were presented by Robert Bersin, MD, at the ISET 2010: International Symposium on Endovascular Therapy in Hollywood, Florida. REFORM is evaluating Cook’s Formula balloon expandable stent for the long-term treatment of renal artery stenosis after suboptimal angioplasty.
According to the company, early data from the single-arm, 100-patient study suggest high technical and procedural success rates, clinically significant reductions in systolic blood pressure at 1 month, stable renal function, and no evidence of safety concerns. Clinical follow-up will continue through 3 years. Enrollment for the European arm of a trial evaluating a drug-eluting version of the Formula stent for renal indications was announced at the LINC 2010: Leipzig Interventional Course meeting held in Germany on January 27-30, 2010.
ISET Presentations Highlight EVAR Treatments for rAAA
January 18, 2010—Research on the treatment of ruptured abdominal aortic aneurysms (rAAAs) was presented at the 22nd Annual International Symposium on Endovascular Therapy (ISET) in Hollywood, Florida on January 17–21, 2010.
Jantje Ten Bosch, MD, presented a study that compared the results of 25 patients who underwent endovascular aneurysm repair (EVAR) to 33 patients who underwent open surgery. All 58 patients were determined to be EVAR-suitable by independent reviewers. Dr. Ten Bosch reported that 4% of patients undergoing EVAR died compared to 6% of patients who died undergoing open surgery. After 6 months, 28% of the EVAR patients and 55% of the open surgery patients had died—a 27% reduction in mortality with EVAR compared to open surgery, which was statistically significant. The average hospital stay for EVAR patients was 8 days compared to an average of 17 days for those who underwent open surgery.
"Although studies have shown EVAR can be used in an emergency situation, this is the first study to compare EVAR and open surgery on a level playing field, because all of the patients were deemed EVAR-suitable," commented Dr. Ten Bosch. "This data strongly suggest that EVAR is a valuable treatment option in EVAR-suitable patients with an rAAA."
Dr. Ten Bosch also presented preliminary research suggesting that a simple blood test may be able to detect when endoleaks in AAAs are occurring, potentially preventing up to 90% of follow-up computed tomography scans, which are costly and involve high doses of radiation and use contrast dye that can damage the kidneys.
According to Dr. Ten Bosch, investigators found that higher concentrations of the blood protein matrix metalloproteinase-9 (MMP-9) accurately predicted which patients had an endoleak. The study included a total of 37 patients, 17 consecutive patients who had an endoleak matched with 20 who did not, all of which were confirmed by computed tomography. All patients with an endoleak had elevated concentrations of MMP-9, compared to only one patient without an endoleak. In that patient, concentrations were only slightly elevated, and investigators determined that MMP-9 concentrations of 55.18 ng ml-1 or greater can identify endoleaks with both high sensitivity and specificity.
"The study is the first to show that concentrations of MMP-9 might accurately discriminate between patients with and without an endoleak," said Dr. Ten Bosch. However, the results must be confirmed by a prospective clinical validation trial, he advised.
FDA to Hold Public Meeting on 510(k) Process
January 22, 2010—The US Food and Drug Administration (FDA) announced that it has scheduled a public meeting on February 18, 2010, to discuss key challenges related to the 510(k) premarket notification process used to review and clear certain medical devices marketed in the United States.
At the meeting, FDA staff will present a brief overview of the challenges the agency has faced, organized in four categories: issues related to predicate devices, which are previously cleared devices that may support a manufacturer’s claim of substantial equivalence; issues related to new technologies and scientific evidence; issues related to practices the FDA has adopted in response to a high volume of submissions; and issues related to postmarket surveillance and new information about marketed devices. Each of the four overview presentations will be followed by an open comment session. The meeting will close with a public roundtable discussion between FDA staff and selected participants representing a range of constituencies.
The February 18 meeting will run from 8 am to 5:30 pm at the Hilton Washington, DC/North Gaithersburg Hotel in Gaithersburg, Maryland. Those interested in attending or participating in the meeting must register by 5 pm on February 12, 2010. The agency is accepting written or electronic comments by March 5, 2010. More information is available from the FDA Web site
|
Free print subscriptions are available to practicing physicians in the US.