Spectranetics (Colorado Springs, Colorado) last month received the best of all good trial news — halt of a study at three-quarters enrollment, with the FDA determining that its early data from the CELLO trial is sufficient. “The FDA agreed that the preliminary data was strong enough to meet the endpoints,” Don Markley, a spokesperson for Spectranetics told Cardiovascular Device Update.
CELLO (pronounced like the instrument) is exploring use of the company’s TURBO-Booster product in clearing blockages in the superficial femoral artery (SFA), and the company had enrolled 61 of the planned total of 81 patients. The SFA is the main artery above the knee, and the company’s TURBO-Booster is a laser/catheter system for removing blockages in that area that can result in severe complications, including amputation of the leg.
The primary endpoint of CELLO included angiographic core lab measurements of the percent reduction in diameter stenosis following treatment with the company’s laser. Other clinical endpoints included 30-day patency using core lab-evaluated duplex ultrasound, improvements in ankle-brachial index and improvement in the ability to walk, 30 days post-procedure.
The TURBO-Booster is a deflecting sheath that is used with Spectranetics’ existing TURBO elite laser catheters. The system is a percutaneous, less-invasive treatment for delivering what it describes as “relatively cool ultraviolet energy to ablate or remove arterial blockages including plaque, calcium and thrombus.” The energy is delivered in pulses via a wavelength of 308 nanometers, vaporizing the clot materials into particles. The UV energy is transmitted along flexible glass fibers encased in catheters, which can be passed through arteries and veins in a procedure the company calls “safer and simpler” than other procedures.
Thus far, the company has focused on using its technology in blockages below the knee, and the above-the knee application provides a much larger opportunity, since it estimates that two-thirds of an estimated 400,000 endovascular procedures in the U.S. are performed to treat blockages above the knee. “This is potentially a transforming event for us, providing the FDA clears the product,” Guy Childs, CFO for Spectranetics, told CDU.
Childs called the data “preliminary.” While he said that both the company and the FDA could characterize the data as “encouraging,” he added: “I would qualify that by saying we still have to gather it all and do all the analysis.”
The trial was single-arm, he said, because there is really no comparison allowing establishment of a control arm in terms of balloon or stent use, especially for treating lesions up to 15 cm, as seen in CELLO. “Balloons have been shown to be ineffective,” Childs said. “They’re used, but the durability of the results is not that good.” Stents used for this type of treatment he characterized as having “a high fracture rate.”
Spectranetics said that follow-up data for CELLO is expected to be gathered early in 2Q07 and an 510(k) application filed with the FDA later in the quarter. The company launched CELLO in July of 2006, the first patient treated being an 72-year-old woman suffering from severe, “lifestyle-limiting claudication.” In that case, the system was used to treat an artery 85% blocked in an artery 6 mm in diameter. At the time, the company said that the stenosis was reduced by 25% and required no follow-on adjunctive treatment with other devices.
John Schulte, president/CEO of Spectranetics, said in a statement, “Completion of the CELLO trial has been our top priority since the trial began nine months ago, and we are pleased that we have concluded enrollment in the trial ahead of our own expectations. We look forward to the opportunity to participate in this large and growing market segment. We will now turn our attention to efficiently gathering and analyzing all of the clinical data from the CELLO trial for our pending submission to the FDA.”
Spectranetics broadened focus to clearance of blockages in the upper legs will put it competitively in a sector currently being developed by Fox Hollow Technologies (Redwood City, California), with its SilverHawk atherectomy device. Rather than using laser energy, the SilverHawk system uses a small rotating blade to shave away plaque from inside the artery. As it is excised, the plaque collects in the tip of the device and then is removed from the patient.
Spectranetics calls its CVX-300 excimer laser the only system approved in the U.S., Europe, Japan and Canada for use in multiple, minimally invasive cardiovascular procedures, including atherectomy — a procedure to remove arterial blockages in the peripheral or coronary vasculature — and the removal of infected, defective or abandoned cardiac lead wires from patients with pacemakers or implantable cardiac defibrillators.
Elsewhere in the product pipeline:
• Cardica (Redwood City, California) reported completing enrollment of about 220 patients in a pivotal clinical trial in U.S. and Europe to evaluate safety/efficacy of its PAS-Port Proximal Anastomosis System during coronary artery bypass graft (CABG) surgery. The PAS-Port system, commercially available in Japan and Europe, creates a secure connection, or anastomosis, between a vein graft and the aorta, the main artery in the human body, during bypass procedures, Cardica said. The trial is being conducted in the U.S. under an Investigational Device Exemption. Two venous bypass grafts were randomly selected in each patient to be connected to the aorta using either the PAS-Port device or the conventional hand-sewn technique. Patients will receive a follow-up angiogram nine months after their procedure to determine patency (degree of openness of the vein graft) of both PAS-Port and control grafts. If the results of this trial are favorable, the company plans to submit a 510(k) application for the PAS-Port system to the FDA in early 2008. The PAS-Port system is designed to allow the surgeon to load the bypass graft and rapidly complete the anastomosis, typically in about two minutes, with little or no injury to the bypass graft vessel or the aorta. Cardica makes automated anastomosis systems for coronary artery bypass graft (CABG) surgery.
Additionally, Cardica reported receiving FDA 510(k) clearance of its C-Port Flex A Anastomosis System in the U.S. The company said that the Flex A system provides modifications of its C-Port xA Distal Anastomosis System product line and further facilitates the automated anastomosis (attachment of blood vessels and grafts) during less-invasive coronary artery bypass grafting (CABG). Cardica said that the design of the Flex A features include a flexible, rather than rigid, shaft, thus providing the ability to create anastomoses in vessels as small as 1 mm in internal diameter; and use in either on- or off-pump CABG. Cardica’s C-Port Distal Anastomosis Systems are marketed in Europe and the U.S. The PAS-Port Proximal Anastomosis System is marketed in Europe and Japan and is being evaluated in a pivotal trial in the U.S. and Europe.
• CardioMEMS (Atlanta) reported that its wireless pressure sensor was surgically implanted into the wrist of three severely hypertensive patients at Hospital DIPRECA (Santiago, Chile) by cardio-thoracic surgeons, Miguel Berr, MD, and Michael Tuchek, DO. Following the implants, Berr said the device “was simple to implant and we expect that the information provided will be very useful in the management of this disease.” The wireless hypertension sensor is positioned just below the surface of the skin above the patient’s radial artery using a minimally invasive procedure. The sensor is designed to allow for a precise and accurate measurement of systemic blood pressure using the CardioMEMS electronics module. The sensor and electronics are designed to allow for additional blood pressure measurements to be taken by the patients at home and to transmit the data wirelessly to a secure database where it will become available for review on CardioMEMS’ patient management website. The wireless hypertension sensor and the related electronics are being evaluated as part of a clinical trial and are not approved for marketing.
•Cleveland Clinic (Cleveland) recently received four U.S. patents in cardiology, ophthalmology and for developing a support pad for surgical patients. The cardiology patent (U.S. Patent No. 7,175,597) was issued for a new noninvasive ultrasound device that provides cardiologists with images of blood vessels, allowing them to assess the vessels’ composition and plaque contents, the clinic said.
• Cook Vascular (Vandergraft, Pennsylvania), a business of Cook Medical (Bloomington, Indiana), reported the launch of the BULLDOG Lead Extender for use during cardiac lead removal procedures. The patent pending device has been designed to help physicians grasp and control cardiac leads that do not have a hollow central lumen. A common technical challenge that physicians can encounter during the removal of these “lumenless” leads is that the short external length of the leads may make the controlled advancement of powered or mechanical extraction sheaths over the lead both difficult and unpredictable. Cook designs products for lead removal.
• CryoCath Technologies (Montreal), a developer of cryotherapy products to treat cardiovascular disease, reported six-month follow up data from 18 patients treated during the feasibility stage of its STOP AF (atrial fibrillation) IDE trial. The trial, now in the pivotal stage, is assessing the company’s Arctic Front catheter to treat atrial fibrillation (AF). This bi-directional, double-balloon catheter enables physicians to rapidly isolate all four pulmonary veins for the treatment of AF. Of the 33 patients treated during the feasibility stage, the second cohort of 18 patients, which have been treated with 23 mm or 28 mm catheters as in the pivotal trial, has now reached the 6-month mark. All patients from the second cohort were free of detectable AF at six months. Three of the patients required a second procedure, which is permissible under the protocol set for the trial. Of these three patients, one is still receiving anti-arrhythmic drug (AAD) treatment. All of the remaining 17 patients are off AAD’s. In comparison to the original 15 patients in the first cohort of which 73% were AFIB free at the six-month mark, the results show “noteworthy improvement,” the company said.
CryoCath also reported receiving FDA approval to expand its pivotal Investigational Device Exemption STOP AF trial for Arctic Front to the full cohort of patients in all 20 centers. The trial is designed to demonstrate Arctic Front’s clinical and therapeutic effectiveness in treating paroxysmal AF when compared to traditional medical therapy. CryoCath develops cryotherapy products to treat cardiovascular disease.
• Edwards Lifesciences (Irvine, California) reported conditional FDA approval to begin a pivotal clinical trial of its Sapien transcatheter aortic heart valve technology. The Placement of Aortic Transcatheter valves (PARTNER) trial will evaluate the Sapien in patients who are considered high risk for conventional open-heart surgery. PARTNER is a randomized clinical trial essentially offering two studies. A surgical category of the study will enroll 350 high-risk patients who are candidates for conventional open-heart surgery. These patients will be evenly randomized to receive either the Edwards Sapien transcatheter heart valve or surgical valve replacement. The clinical results of this arm will need to demonstrate that the Sapien valve is not statistically inferior to conventional surgery. The medical management study of the trial will enroll 250 patients who are considered too high risk for conventional open-heart surgery. Those patients will be evenly randomized to receive either the Edwards Sapien transcatheter heart valve or appropriate medical therapy, as prescribed by the physician. The clinical results of this arm will need to demonstrate that the Sapien valve is statistically superior to medical management. The primary endpoint in both arms of the trial is mortality at one year with secondary endpoints that focus on all aspects of valve performance and quality-of-life indicators. Each arm of the trial contains a sufficient number of patients to support independent statistical analysis, according to Edwards. Wood said the company designed the trial to essentially be two trials in one because the control groups in the two study arms are very different — one control group will be receiving medication as treatment for aortic stenosis while the other control group undergoes open-heart surgery. The Edwards Sapien transcatheter aortic heart valve integrates balloon-expandable stent technology with a replacement tissue heart valve. The Sapien valve is compressed onto the balloon to about the diameter of a pencil and is threaded through the patient’s circulatory system from either the leg or it is inserted between the ribs and expanded directly over the aortic valve. The therapy was originally developed in conjunction with Alain Cribier, MD, chief of cardiology at the University Hospital (Rouen, France), who performed the first transcatheter valve replacement in April 2002, the company said.
• The FDA earlier this year gave Evalve (Menlo Park, California) the go-ahead to expand to a higher-risk surgical group the use of its MitraClip product for percutaneous repair of mitral regurgitation (MR). This is being done via approval of a 70-patient, single-arm registry of these high-risk patients, in addition to the company’s ongoing randomized Endovasulcar Valve Edge-to-edge REpair STudy (EVEREST) of the Mitraclip which involves only a low-risk surgical candidates. Selecting the patients for the registry will be based on a determination of operative mortality risk for each patient’s condition. The company worked with the FDA collaboratively, making the decision to use a risk calculator, developed by the Society of Thoracic Surgeons (Chicago) which will include those patients at risk for operative mortality — in the surgical procedure — at 12% or greater. The hope, of course, is that treatment with the Mitraclip will prove to be much lower risk.
• Haemonetics (Braintree, Massachusetts) reported FDA clearance and U.S. launch of the Cymbal system, a portable system for collecting two units of red blood cells from one blood donor in a single donation. At half the size of Haemonetics’ first generation technology, the Cymbal system can be battery-operated and meets blood collectors’ need to cost effectively collect more blood on community blood drives. The consumable used with the device is designed to allow blood collectors to leuko-reduce the red cells during the collection process, saving processing time and cost. Leuko-reduction removes white blood cells that can potentially be harmful if transfused to a patient.
• Immucor (Norcross, Georgia), a provider of automated instrument-reagent systems to the blood transfusion industry, said that it made a 510(k) premarket notification submission to the FDA for its Galileo Echo instrument. Immucor makes reagents and systems used by hospitals, reference laboratories and donor centers to detect and identify certain properties of the cell and serum components of blood prior to transfusion.
• MedicalCV (Minneapolis) reported FDA 510(k) clearance for its Solar Surgical Ablation System for the ablation of soft tissue. MedicalCV said it developed the Solar System to enable automated, computer-controlled ablation in surgical procedures using laser energy. The company makes surgical ablation systems that utilize a laser energy technology platform to create precise lesions, or scars, on soft and cardiac tissues. The company’s core technologies are the Solar and Atrilaze Surgical Ablation Systems for use in soft and cardiac tissue ablation procedures, respectively.
• Medtronic (Minneapolis), the latest company vying to get its Cardioblate system okayed for atrial fibrillation, reported that it has begun a U.S. pivotal clinical trial for the Cardioblate surgical ablation system to treat the cause of permanent AF via a different approach than it pursued in its initial foray. That effort came in 2004, with the Cardioblate Atrial Fibrillation (CAF ) study for treatment of AF. Now, the FDA has approved the company to conduct a prospective, non-randomized, clinical trial — Concomitant Utilization of RadioFrequency Energy for Atrial Fibrillation (CURE-AF) — which will enroll 75 patients at 10 U.S. medical centers. The primary endpoints of the trial are to evaluate the freedom from permanent AF in patients off antiarrhythmic drugs at six months, with the composite major adverse event rate at one month.
• Possis Medical (Minneapolis) reported market release of its new AngioJet ultra thrombectomy system, FDA-approved in December. The system is the latest version of the ultra thrombectomy system that has been used in more than 300,000 patients worldwide for thrombectomy in arterial and venous blood vessels. The new micro-processor-based ultra system reduces setup time, improves mobility and provides a self-prompting, much simpler control interface, according to the company. Possis makes devices used in endovascular procedures.
• Saint John’s Health Center (Santa Monica, California) reported that a cardiologist used an investigational, endoscopically guided laser catheter to treat “short-circuiting” heart tissue that was causing a potentially dangerous arrhythmia in a 58-year-old man. The investigational device used in this procedure is called Visually Guided Endsocopic Ablation System and was developed by CardioFocus (Marlborough, Massachusetts). The patient was the first patient to be treated in the ENABLE trial, a multi-center investigation at 20 hospitals. Director of cardiac electrophysiology, Shephal Doshi, MD, performed the investigational procedure, called Endoscopic Catheter Ablation, on the California man who had suffered from periodic episodes of irregular heartbeat, dizziness and fatigue for more than a year. He was diagnosed with atrial fibrillation. Doshi and colleagues inserted a slender catheter into a vein in the patient’s right leg up into his chest and guided into a large vein in his heart, using the investigational endoscopic video camera, small amounts of traditional real time X-ray and ultrasound imaging. Doshi inflated the balloon and was able to visualize the target tissue for the first time. Once the target was located, he turned on the laser, which released precisely controlled arcs of light around the vein. Several bursts of laser energy were able to destroy an area of abnormal tissue while causing no significant damage to surrounding healthy heart muscle.
• Stereotaxis (St. Louis) reported initiating the HEAL HF clinical trial, to evaluate the ability to magnetically navigate to multiple potential pacing sites and then optimize LV lead placement to treat heart failure. The case included the evaluation of seven pacing sites in the left ventricle, which exhibited significant differences from site-to-site in the hemodynamic response of the patient’s heart, measuring cardiac function. The Stereotaxis magnetic guided lead placement system is designed to enable physicians to complete more complex interventional procedures by providing image guided delivery of catheters and guidewires through the blood vessels and chambers of the heart to treatment sites. This is achieved using computer-controlled, externally applied magnetic fields that govern the motion of the working tip of the catheter or guidewire, resulting in improved navigation, shorter procedure time and reduced x-ray exposure. Stereotaxis makes cardiology instrument control systems.
• St. Jude Medical (St. Paul, Minnesota) reported introducing a new feature into its cardiac rhythm product offerings to help treat patients with heart failure (HF). It said it received FDA approval of a new cardiac rhythm management device — called the Atlas II+ HF CRT-D (cardiac resynchronization therapy defibrillator) - designed to help physicians manage heart failure (HF) patients, including patients who have or may develop atrial fibrillation (AF). The company said the device is the first U.S. HF system to offer the AF Suppression algorithm. This algorithm helps maintain control of the heart’s atrial rhythm by pacing slightly faster than the patient’s natural heart rate. The AF Suppression algorithm has been clinically proven to reduce the AF burden (the percentage of days with AF symptoms) in previous studies.
• SyntheMed (Iselin, New Jersey) reported that the FDA has accepted its pre-market approval application for Repel-CV adhesion barrier for review. Repel-CV is a bioresorbable film designed to be placed over the surface of the heart at the conclusion of an open-heart surgical procedure to reduce post-operative adhesions. In September 2006, SyntheMed reported positive efficacy results from its multi-center, randomized, masked pivotal clinical trial of Repel-CV in neonatal patients who underwent staged, open-heart surgical procedures, conducted at 15 U.S. pediatric cardiac surgery centers and enrolling 144 neonatal patients. Surgeons used a four-point grading system to determine the extent and severity of adhesions in the patients. More than 70% of the Repel-CV treated patients were completely free of clinically-significant adhesions, the most severe grade of adhesions measured, as compared to less than 30% in the control patients, with a p value < 0.0001. In the primary clinical endpoint assessment, the mean extent of clinically-significant adhesions in the control patients was 2.5 times greater than in the Repel-CV patients, with a p value = 0.0005. Repel-CV is marketed through a network of independent distributors in the European Union and in several Southeast Asian countries.
• VNUS Medical Technologies (San Jose, California) said that the first report of six-month follow-up clinical results from a trial of the ClusureFAST endovenous radio frequency (RF) vein ablation catheter was given at the American Venous Forum meeting. In the study, treatments with the ClosureFAST catheter resulted in an average energy delivery time of 2.2 minutes, and the average procedure time (measured from catheter insertion to catheter removal, including the time for the administration of tumescent anesthesia) was 16.4 minutes. The ClosureFAST catheter is designed to heat, shrink and occlude refluxing saphenous veins with RF ablation times of just three to five minutes while maintaining the fast and mild patient recovery that physicians expect with RF vein ablation. VNUS makes products for the minimally invasive treatment of venous reflux disease.
• Zoll Medical (Chelmsford, Massachusetts) reported that it has received FDA to market the ZOLL M Series with Real CPR Help technology, enabling rescuers to instantly see and hear how well they are performing the rate and depth of CPR chest compressions. The company said that the M Series is its best-selling product to date. “Virtually all of the products we market now incorporate Real CPR Help technology to improve the quality of CPR that rescuers provide,” said Richard Packer, President/CEO of Zoll. CPR achieves effective blood flow to feed oxygen to the heart and brain and is associated with a return of a “shockable” heart rhythm, making defibrillation possible later in the resuscitation event. Zoll provides technologies that help clinicians, EMS professionals, and lay rescuers resuscitate sudden cardiac arrest or trauma victims.
• Xtent (Menlo Park, California) reported the enhanced configuration of its Custom NX Drug Eluting Stent (DES) system used successfully in its CUSTOM III clinical trial in Europe. The company also reported that its U.S. pivotal trial is on track to begin with this system in the second half of 2007 as planned. The upgraded Custom NX features a smaller crossing profile and an improved user interface designed to further enhance stent placement accuracy and ease of use while decreasing procedure time, complexity and cost. The device is designed to enable “a more personalized approach to arterial disease based on each patient’s individual lesion characteristics, improving ease of use and placement accuracy while decreasing procedure time,” according to Xtent. The Custom NX system consists of a series of DES segments, allowing physicians to customize the stent length while inside the patient’s affected arteries. Physicians can shorten, reposition and reinflate the delivery balloon at the treatment site for post-dilatation if necessary. After the first stent deployment, the Custom NX can be reset and used to treat additional lesions. As a result, the Custom NX has the potential to treat single, long and multiple lesions with one device. The company says that, in comparison, current fixed length systems often require multiple stents, balloons and catheter exchanges. More than half of stent patients have lesions in more than one vessel and approximately one in four procedures involve overlapping stents. Custom NX is the only DES system designed specifically to treat these patients. Xtent is focused on developing “customizable” DES systems for the treatment of coronary artery disease.