A Medical Device Daily

While some of the bigger medical device companies such as Medtronic (Minneapolis) and Boston Scientific (Natick, Massachusetts) are getting their share of the spotlight this week at Transcatheter Cardiovascular Therapeutics 2009, there are some smaller companies at TCT this week that also have promising technology to talk about.

Among them, Mardil (Morrisville, North Carolina) reported positive interim data from a pilot study in India investigating the safety and efficacy of its new cardiac device – Basal Annuloplasty of the Cardia Externally (BACE) – in treating mitral valve regurgitation. The condition arises when the heart's mitral valve leaks blood backward into the heart, causing a range of severe and debilitating symptoms. Mardil is seeking an investigational device exemption through the FDA to begin clinical trials in the U.S. next year.

According to the data, the first 11 patients implanted with BACE demonstrated a significant reduction in the severity grade of their mitral regurgitation, from a baseline mean grade of 3.32 to a mean grade of 0.61 post implantation. Mitral regurgitation severity is graded on a scale from 0 to 4, with 4 representing the most severe condition. The improvements in mitral valve function were sustained at six months, as demonstrated by follow-up echocardiograms conducted in the three of the 11 patients. No device related adverse events were reported.

"While the data are preliminary, they represent a level of improvement that is extremely encouraging," said Jai Raman, MD, PhD, professor of surgery and director of adult cardiac surgery and cardiothoracic surgical research at the University of Chicago. "BACE represents a novel modality for treating functional mitral valve regurgitation because it addresses the root cause of the condition – a heart muscle that is enlarged and weakened – whereas current devices on the market attempt to replace or repair valves that are structurally normal."

Mardil said the pilot study of 20 patients was designed to assess the safety and efficacy of the BACE device, a less invasive cardiac device that sits outside the heart and supports the weakened ventricular muscle while treating valvular dysfunction. Eleven patients with moderate to severe ischemic mitral regurgitation underwent implantation with BACE, along with coronary artery bypass grafting (CABG) on a beating heart; seven of them underwent surgery without a heart-lung bypass machine. Three patients had left ventricular reconstructive procedures. One patient died of complications related to insertion of a mechanical support device that was placed pre-operatively, the company said. No device-related adverse reactions were reported in the trial.

The pilot study is being conducted in India. Mardil is seeking an investigational device exemption through the FDA to begin clinical trials in the U.S. next year.

The BACE device serves as a tension band that encircles the exterior of the heart, supporting the left ventricular wall and the mitral valve annulus. Gentle pressure and support from the BACE allow the leaflets of the mitral valve to close properly, thereby preventing blood from leaking backward when the heart pumps. According to the company, BACE is the only device that can be adjusted and fine-tuned after implantation and in an office setting. The device was designed to reduce the significant mortality and morbidity rates associated with current treatments for mitral valve repair and replacement. The device sits outside the heart, negating the need for open-heart surgery or the use of a heart-lung bypass machine, both of which pose serious risks and side effects.

In other TCT news:

• Boston Scientific reported one-year data from the SPIRIT IV trial comparing the Xience V (Promus) everolimus-eluting coronary stent system to the Taxus Express paclitaxel-eluting coronary stent system. The results support the benefits of paclitaxel-eluting stents in diabetic patients, the company noted. The trial enrolled 3,690 patients, including 1,140 diabetics, the largest diabetic subset ever studied in a drug-eluting stent (DES) clinical trial, according to Boston Scientific.

Abbott (Abbott Park, Illinois) makes the Xience V everolimus-eluting stent, which won FDA approval in July 2008, but Boston Scientific shares profits from the device. Guidant (Indianapolis) had been developing the stent and when Boston Scientific acquired the company, it had to divest the stent to Abbott, but it retained the right to sell the same device as the Promus under a private-label arrangement (MDD, July 7, 2008).

Boston Scientific also reported that on Oct. 1 it will begin its previously planned, phased discontinuation of the Taxus Express stent used in the SPIRIT IV trial. The Taxus Express has been replaced by the thinner-strut Taxus Liberte stent worldwide. The Taxus Liberte was approved in Europe in 2005, in the U.S. in 2008 and in Japan this year.

The company reported that the target lesion failure (TLF) rates for diabetic patients at one year were 6.4% for the Xience V (Promus) stent and 6.9% for the Taxus Express. For diabetic patients requiring insulin, the TLF rates were 8% for the Xience V (Promus) and 7% for the Taxus Express.

SPIRIT IV is a prospective, single-blinded, multicenter clinical trial in which patients with up to three native coronary artery lesions were randomized 2:1 to the Xience V (Promus) stent or the Taxus Express at 66 U.S. sites. The primary endpoint is the rate of ischemia-driven TLF at one year, which is a composite measure of safety and efficacy consisting of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization (TLR).

The results showed the trial met its endpoint of TLF non-inferiority with rates of 4.2% for the Xience V (Promus) and 6.8% for the Taxus Express. Contributing to this result was a significant difference in TLR (2.5% for Xience V versus 4.6% for Taxus Express), including a large subgroup of patients (1,352) with vessels smaller than or equal to 2.75 mm. The company also reported this week that the TAXUS ATLAS Small Vessel Trial reported a statistically significant reduction in the rate of TLR in small vessels treated with the 2.25 mm diameter Taxus Liberte Atom stent compared to the older 2.25 mm diameter Taxus Express Atom stent.

SPIRIT IV safety results demonstrated comparable rates of death (1% for Xience V versus 1.3% for Taxus Express) and a non-significant difference in myocardial infarction (1.9% for Xience V versus 3.1% for Taxus Express). The overall major adverse cardiac events (MACE) rate was 4.2% for Xience and 6.9% for Taxus Express). Stent thrombosis under the Academic Research Consortium definite/probable definition was 0.29% for Xience versus 1.1% for Taxus Express. This difference is inconsistent with results seen in the SPIRIT II and III trials where rates of ARC stent thrombosis were comparable at one year and remained similar out to three years, Boston Scientific noted.

The Taxus Liberte has received an indication for use in diabetic patients in CE-marked countries. In the U.S., the Taxus Express, Taxus Liberte and Promus stents are not specifically indicated for use in diabetic patients.

• Medtronic (Minneapolis) said that more presentations than ever before – at least 25 – on its transcatheter valves are being presented at TCT this week.

Most of the new clinical data on this medical technology at the meeting focuses on the Medtronic CoreValve Percutaneous Aortic Valve System, which is designed to replace a diseased aortic heart valve without open-heart surgery and without surgical removal of the failed valve. The device is typically delivered through the femoral artery, the company noted. Commercially available internationally, the CoreValve system is investigational in the U.S.

Medtronic said that on Monday it highlighted the successful clinical performance of the Medtronic CoreValve system. Presentation of the European/Canadian 18Fr safety and efficacy study included two-year patient follow-up data, the longest of any transcatheter aortic valve, highlighting the safety, efficacy and durability of Medtronic CoreValve. Also presented were strong safety and efficacy results from the ANZ Registry, which tracks outcomes of CoreValve patients at several centers in Australia and New Zealand. In all, the summit featured 13 consecutive scientific presentations on the CoreValve system, the company said.

The TCT program also includes data presentations on Medtronic's other transcatheter valves: the Melody transcatheter pulmonary valve, which is commercially available internationally but not yet approved in the U.S.; and the Ventor transcatheter aortic valve, which is investigational worldwide.

The Medtronic Ventor system is designed to be delivered via minimally invasive surgery through the apex of the heart. Patients with aortic stenosis who are not candidates for transfemoral delivery – sometimes because of peripheral artery disease – may be candidates for a transapical approach. The Medtronic Melody system is designed to address the effects of a dysfunctional pulmonary valve without opening the chest for surgery; it is delivered through the femoral vein.

• Toshiba America Medical Systems (Tustin, California) introduced its Next Generation CV-3DTM workstation and software package available on the InfinixTM-i X-ray product line. Next Generation CV-3D is an integrated reconstruction workstation and software, designed to take a 2-D X-ray image and reconstruct a new, more detailed 3-D image in a matter of seconds, the company said.

According to the company, the new image provides a 3-D reconstructed view of the same vessel under study, allowing physicians to determine the best treatment plan. CV-3D visualization assists physicians in selecting the most appropriate stent, potentially reducing the need for additional invasive devices, Toshiba said. Some of the latest enhancements optimize stent selection and positioning by automatically including markers in the view and providing a clear view of the stent in relationship to the vessel wall, which validates proper stent deployment. Clinicians also can increase workflow by utilizing the Infinix-i tableside controls to display the preferred CV-3D image in the examination room, the company noted.

• Elixir Medical (Sunnyvale, California) reported positive results from three multicenter first-in-man studies of its Novolimus and Myolimus eluting coronary stent systems with durable and bioabsorbable polymers. Nine-month clinical and six-month angiographic and IVUS results from the first-in-man study of Novolimus eluting coronary stent system with Elixir's bioabsorbable polymer were presented by Alexandre Abizaid, MD, PhD on behalf of the study investigators. At nine months, the Novolimus eluting coronary stent system demonstrated excellent efficacy and clinical safety with no MACE events or incidents of stent thrombosis. Six-month angiographic and IVUS follow-up demonstrated an in-stent late lumen loss of 0.16 0.23 mm and a volume obstruction of 1.6 0.9%.

Six-month clinical, angiographic and IVUS results from the first-in-man study of the Myolimus eluting coronary stent system with the lowest known dose of an olimus' drug and Elixir's bioabsorbable polymer were presented by Bernard Witzenbichler, MD, of Charite Campus Benjamin Franklin (Berlin, Germany) on behalf of the study investigators. At the six-month follow-up for 30 patients, there were two non Q-wave myocardial infarctions and one target lesion revascularization. There were no incidents of stent thrombosis. Six-month angiographic and IVUS follow-up demonstrated an in-stent late lumen loss of 0.08 0.16 mm and a volume obstruction of 3.2 3.0%.

Twenty-four-month clinical results from EXCELLA I, the first-in-man study of the Novolimus eluting coronary stent system with a durable polymer, were presented by Alexandre Abizaid, MD, PhD, of the Institute of Dante Pazzanese de Cardiologia (Sao Paulo, Brazil). At 24 months, the Novolimus eluting coronary stent system demonstrated sustained efficacy and clinical safety with no incidents of stent thrombosis, the company reported.

The EXCELLA II randomized clinical trial completed patient enrollment in the first quarter of 2009. The study enrolled 210 patients in Europe and Asia Pacific. Patients are currently undergoing the nine-month clinical, angiographic, and IVUS follow-up. Data from the trial will be submitted for CE Mark approval, Elixir said.

• OrbusNeich (Hong Kong) reported that interim data from a prospective registry showed good safety in a broad population of patients that underwent primary percutaneous coronary intervention and implantation of the company's Genous Bio-engineered R stent for ST-elevation myocardial infarction (STEMI).

In the study of 652 consecutive STEMI patients, the rate of MACE was 6.7% and the rate of subacute thrombosis was 1.1% at 30 days follow up. The interim data were presented in a poster by Jan-Henk Dambrink, MD, PhD, of the Isala Klinieken (Zwolle, Netherlands).

Eleven percent of the patients in the study of 652 consecutive STEMI patients were diabetic, 41% had an anterior infarction, 6% were in heart failure, and 6% received an intra-aortic balloon pump. Half of the 23 patients who died were initial survivors of out of hospital cardiac arrest.