St. Jude Medical (St. Paul, Minnesota) reported the enrollment of the first patient in its ESCAPE (Effect of Septal Closure of Atrial PFO on Events of Migraine with Premere) migraine trial, making it the first company to begin enrollment in a U.S. clinical trial to evaluate the connection between patent foramen ovales (PFOs) and migraine headaches.

The trial is a prospective, randomized, two-arm, double-blind multicenter trial, with the objective to determine if patients who undergo a PFO closure procedure have a decreased number of migraines over one-year follow-up as compared to those who are maintained only on drug therapy. The trial uses the company’s Premere system, acquired via its $74 million purchase of Velocimed (Maple Grove, Minnesota) last April.

The ESCAPE trial will be conducted at 45 headache clinics and 15 interventional cardiology clinics throughout the U.S.

According to St. Jude, critical features of its Premere PFO closure system include: flexible, low-profile anchors that conform to the septal wall; independent anchors to position for precise placement; limited surface area and prosthetic material designed to encourage rapid endothelialization and minimize the incidence of thromboembolic complications; and an adjustable tether to adapt to varying patient anatomies.

While the Premere PFO closure system is CE-marked, it is not yet labeled in Europe for the treatment of migraines.

The first patient, a Virginia woman, will be one of more than 500 patients to participate in the study, which received approval from the FDA for an investigational device exemption (IDE) in December 2005 after receiving its conditional approval for the trial last August.

While St. Jude is the first company to begin U.S. enrollment in a migraine trial, it is most definitely not the only one seeking a slice of this potentially lucrative new market. Other competitors include what many consider to be the current market leader in this sector, NMT Medical (Boston), whose StarFlex system is being evaluated in the UK-based MIST I (Migraine Intervention with STARflex Technology) trial. In October, the company also received FDA approval for an investigational device exemption (IDE) to initiate a 600-patient pivotal PFO/migraine clinical study, dubbed MIST II, which had not begun enrollment as this issue of Cardiovascular Device Update went to press.

Another competitor, AGA Medical (Golden Valley, Minnesota), has recently entered the fray with a conditional approval from the FDA in February for its PREMIUM (Prospective Randomized investigation to Evaluate the incidence of headache reduction in subjects with Migraine and PFO Using the Amplatzer PFO Occluder compared to Medical Management) trial. PREMIUM, which is expected to enroll about 400 patients at up to 30 medical centers, is a prospective, randomized, two-arm, double blind multicenter trial designed to determine whether patients who undergo closure of a PFO with the company’s Amplatzer device have a reduction in both the frequency and severity of migraine headaches.

Cardia (Burnsville, Minnesota), with its Intrasept device, is enrolling patients in Europe in its FORMAT (Patent Foramen Ovale Closure to Reduce Migraine Attacks) trial.

The association between PFOs and migraine headaches was first observed by physicians who treated PFOs to remedy other medical conditions such as stroke; these physicians later noticed a reduced frequency in patients’ migraine headaches. Additional informal studies have shown reduced pain – after PFO closure – for migraine patients. It is not clear why patients with a PFO would be more likely to have migraines, or why closing the PFO might decrease migraine attacks. Some physicians speculate that blood that crosses the PFO, without being filtered by the lungs, has substances that trigger migraines.

Elsewhere in the product pipeline:

• Abbott (Abbott Park, Illinois) on Friday introduced a new specialty catheter designed to help physicians access areas of blockage in the coronary arteries and other vessels in the body that may be difficult to reach. Known as the Asahi Tornus specialty catheter, the new stainless-steel device is engineered to deliver therapeutic, minimally invasive balloon catheters and stents to vessels blocked with dense fibrous fatty plaque – also known as chronic occlusions. Bonnie Cheng, director of strategic marketing for coronary products at Abbott Vascular (Redwood City, California) told CDU that the catheter is “certainly unique” and that it is the only “specialty catheter” of this type that’s in the market. The catheter was launched at the Third International Chronic Total Occlusion Summit in New York early last month, and the product is available now in the U.S. There is no question there is demand for the device, Cheng said. Research has demonstrated that about 30% of patients with coronary artery disease have at least one chronic occlusion, the company said. The device is available in two sizes: 2.1 Fr for accessing lesions that are more difficult to navigate and 2.6 Fr for circumstances requiring more support to push through the lesion. The Tornus is manufactured by Asahi Intecc (Aichi, Japan). Abbott has a licensing agreement with Asahi Intecc to distribute its guidewires in the U.S. and certain countries worldwide.

• Cardiac Science (Bothell, Washington) reported that the FDA has granted the company 510(k) regulatory clearance to market a new “crash cart” defibrillator-monitor designed specifically for use by medical professionals to respond to cardiac emergencies in hospital settings. The new defibrillator will be sold exclusively by GE Healthcare (Waukesha, Wisconsin) to hospitals in the U.S. and Canada under the Cardiac Science Powerheart brand, and to customers outside North America under the GE Responder brand. Initial shipments are expected to take place during 2Q06. The new defibrillator-monitor is a lightweight, rugged and portable device with resuscitation and pacing therapies. Operators are guided by a combination of programmable text prompts, audible alarms and visible indicators. The defibrillator-monitor incorporates the company’s STAR biphasic escalating shock energy technology, which automatically adjusts the magnitude of the defibrillation shock based upon each patient’s body type and also employs Cardiac Science’s RHYTHMx software, which provides heart rhythm analysis and shock advice to effectively address life- threatening arrhythmias.

• CardioDynamics (San Diego), a developer of impedance cardiography (ICG) technology, reported publication of data from the ED-IMPACT trial, which demonstrated that information from its BioZ ICG device resulted in a change in treatment 39% of the time and a change in emergency department diagnosis 13% of the time in patients presenting with shortness of breath. The results were published online in Academic Emergency Medicine, and will be published in this month’s print version of the journal.

• Cardiogenesis (Foothill Ranch, California), manufacturer of surgical products and accessories used in angina-relieving transmyocardial revascularization (TMR) procedures, reported the publication of an Expert Review of Medical Devices focused on the company’s Holmium:YAG TMR system in the March edition of Future Drugs. Author Keith Allen, MD, of the Heart Center of Indiana (Indianapolis), concluded: “Angiogenesis is the most likely mechanism of action responsible for clinical improvement following TMR, and research should be continued to find ways to augment this process.”

• Clinical Data (Newton, Massachusetts), which is commercializing pharmacogenomics to guide drug utilization, reported that its Vital Diagnostics division has received FDA clearance to market a wide-range C-reactive protein (wrCRP) assay, trademarked as the Nanopia wrCRP Assay. The Nanopia wrCRP is an in vitro diagnostic used for the quantitative measurement of C-reactive protein in serum or plasma. C-reactive protein is a blood component that increases rapidly in infections, tissue trauma, surgery or other injury to the body.

• Cytori Therapeutics (San Diego) reported the publication of a summary of peer-reviewed research, authored by Cytori scientists, on the potential of adipose stem cells in cardiac cell therapy. The article, which appeared in the March 3 issue of Cardiovascular Medicine Supplement of Nature Clinical Practice, highlights the proposed mechanisms by which adipose stem cells contribute to the repair of damaged cardiac muscle, specifically the angiogenic effects and the prevention of cell death as primary mechanisms as well as differentiation into new cardiac muscle. Additionally, the article points to the ability to obtain a high yield of adipose stem cells from patients in real-time with relative ease compared to bone marrow and other adult stem cell sources. The functional benefit has been observed in multiple pre-clinical studies.

• ev3 (Plymouth, Minnesota) reported FDA 510(k) clearance of the SpideRX Embolic Protection Device for use in carotid artery stenting applications. ev3 is prepared to release the product immediately for commercial sale. The device is designed to provide efficient delivery, capture and recovery while allowing interventionalists to use their interventional wire of choice. Improvements over the Spider Over-the-Wire system include a complete rapid exchange system, 6 Fr guide catheter compatibility and a dual-end delivery/recovery catheter with a pre-loaded capture wire.

• FoxHollow Technologies (Redwood City, California) reported that a multicenter evaluation of patients with critical limb ischemia found that 82% of patients who received plaque excision avoided an amputation or received a less extensive amputation than originally planned. Results of the study were published in the February issue of the Journal of Endovascular Therapy. The patient population was comprised of those who suffer from the most severe form of peripheral artery disease (PAD). Six months after the plaque excision procedure, 96% of the lesions remained free from re-treatment in patients without amputation. Patients enrolled in the study were treated with the company’s SilverHawk Plaque Excision System, a device used to remove plaque caused by PAD and restore blood flow to the legs, feet and toes.

• GE Healthcare (Waukesha, Wisconsin) reported FDA 510(k) clearance for the Innova 3131^IQ and 2121^IQ digital flat panel biplane imaging systems at the American College of Cardiology (Bethesda, Maryland) annual scientific sessions in Atlanta. Both systems are indicated for use in cardiovascular imaging, diagnostic and interventional procedures, and 3-D imaging of vessels and soft tissue. The Innova IQ platform is capable of imaging the finest vessels and cardiovascular anatomy based on the company’s digital flat panel technology. With the 20cm and 30cm area coverage, the Innova Biplane systems are the first to cover the full size of the patient’s lateral and frontal anatomy simultaneously, GE said.

• Guidant (Indianapolis) reported enrollment of the first patient in a first-in-man clinical trial designed to evaluate the safety of a fully bioabsorbable everolimus-eluting stent platform for the treatment of coronary artery disease. The trial, called ABSORB, will enroll up to 60 patients in Belgium, Denmark, France, New Zealand, Poland and the Netherlands. “As the world’s first clinical trial evaluating a fully bioabsorbable drug-eluting coronary stent, this initial implant marks a significant milestone for Guidant. This study will lay the foundation for our continued work toward offering a valuable alternative to current drug eluting stent implants that reside permanently in the treated coronary artery,” said John Capek, PhD, president of Guidant’s Vascular Intervention business. The ABSORB trial will study the safety of bioabsorbable drug-eluting stents developed by Bioabsorbable Vascular Solutions (Santa Clara, California), a subsidiary of Guidant Vascular Intervention. These stents are designed to be fully absorbed by vascular tissue following the restoration of blood flow and drug elution in patients with coronary artery disease. Guidant has completed extensive preclinical studies on its bioabsorbable stent, gathering data on safety, drug dosing, and the mechanical properties of the stent. ABSORB is a non-randomized study with an initial assessment of safety (MACE and stent thrombosis rate) at six months and a follow-up period of five years. The first implant was performed by a team headed by John Ormiston, MD, and Mark Webster, MD, at Auckland City Hospital (Auckland, New Zealand). Ormiston and Patrick Serruys, MD, of the Thoraxcenter at Erasmus University Hospital (Rotterdam, the Netherlands), will serve as the study’s co-principal investigators.

• Kensey Nash (Exton, Pennsylvania) reported that a low MACE rate of 3.2% was achieved in its recent ASPIRE study, which studied the effectiveness of the new TriActiv FX Embolic Protection System to reduce MACE during the treatment of diseased saphenous vein grafts (SVG). The company said that the 3.2% rate is the lowest recorded to date from a sizable multicenter study of the SVG population, and is less than half of the next best data set widely quoted by the cardiology community. The rate of heart attacks in the ASPIRE study, included as part of the MACE rate, was a low 2.2%, which is a 67% reduction in the rate seen in the next-best embolic protection device’s data set, the company said. It also noted that procedure times were on average 15 minutes below the control cohort of the other embolic protection systems. The complete data set from ASPIRE was highlighted during last month’s American College of Cardiology conference in Atlanta.

• Medtronic (Minneapolis) reported the addition of OptiVol Fluid Status Monitoring trend data available via the Medtronic CareLink Network. OptiVol Fluid Status Monitoring, which measures changes in impedance in the thoracic cavity, is a feature found on the InSync Sentry cardiac resynchronization therapy-defibrillator. Using low electrical pulses that travel across the thoracic cavity, the system can measure the level of resistance to the electrical pulses, which indicates the level of fluid in the chest. Since normal fluid levels may vary from patient to patient and fluid accumulation can be either slow or rapid, OptiVol’s ability to measure fluid status trends over time can provide insights that are used in conjunction with ongoing monitoring of other patient symptoms. The company recently received FDA approval to provide this fluid trend data to physicians monitoring their patients via the Medtronic CareLink Network.

• Possis Medical (Minneapolis) reported the recent publication of a clinical study that included its AngioJet Rheolytic Thrombectomy Catheter System. The study evaluated clinical outcomes in high-risk acute coronary syndrome patients whose initial treatment with thrombolytic drugs had failed, and who therefore required urgent, rescue percutaneous catheter-based intervention (PCI). More than 200 patients were included in the study, which appears in the February issue of Catheterization and Cardiovascular Interventions. Of these, 21% received AngioJet treatment as part of the rescue PCI. The authors concluded that “angiographic and clinical success was high with low bleeding complications and low in-hospital mortality.” Dr. Ray Matthews, who conducted the study with colleagues at Good Samaritan Hospital and the UCLA Medical Center (Los Angeles), will participate in a roundtable discussion of AngioJet coronary thrombectomy, hosted by Possis Medical, during the March meeting of the American College of Cardiology in Atlanta.

• Sorin Group (Milan, Italy), Europe’s largest cardiovascular device company, presented at the JIM congress in Rome the first six-month clinical results from its e-Janus international “real-world” registry. The company said the data confirm that the Janus tacrolimus-eluting Carbostent provides excellent safety profile and clinical efficacy for the treatment of real-world patients, including the high-risk AMI (acute myocardial infarction) patient population. While still recruiting, the e-Janus registry has currently enrolled more than 2,500 patients at more than 80 centers worldwide. Six-month clinical follow-up on 587 patients showed reported a 4.3% MACE rate and a 3.1% target lesion revascularization (TLR) rate. Results achieved in the AMI subset of 133 patients included a 3% MACE rate at six-month follow-up, and a TLR rate of 2.2%. The late stent thrombosis rate for this high-risk subgroup was 0%, which the company said demonstrates the excellent safety profile on the thromboresistant Janus platform.

• Stereotaxis (St. Louis) reported that Central Baptist Hospital (Lexington, Kentucky) became the first U.S. center to treat a patient’s cardiac arrhythmia using the company’s partnered 3-D Localized Ablation Catheter. This diagnostic and ablation catheter recently received FDA approval for use with the Stereotaxis Niobe Magnetic Navigation System. The company said the approval provides Stereotaxis Niobe system users in the U.S. with 3-D localization of the catheter tip, a function that offers physicians precise and efficient control of the catheter tip with constant feedback as to the exact location of the catheter in the anatomy.

• Tensys Medical (San Diego) said a new study published in the February issue of Anesthesia and Analgesia shows that the noninvasive Tensys T-line provides continuous beat-to-beat blood pressure (BP) measurement with comparable accuracy to that of an invasive radial arterial catheter (A-line). Researchers evaluated the T-line device in the operating room with patients undergoing general anesthesia. Systolic, diastolic and mean BPs were compared from the T-line and the contra-lateral A-line. The mean errors reported were 1.7 +/- 7.0 for systolic, 2.3 +/- 6.9 for diastolic and 1.7 +/- 5.3 for mean. The noninvasive arterial waveforms produced from the T-line emulated those of the contra-lateral arterial catheters. The researchers concluded that the T-line provides an accurate noninvasive alternative for beat-to-beat blood pressure management.

• TransMedics (Andover, Massachusetts), which is developing organ transplant technologies, reported the initiation of the European PROTECT (PROspective multicenter European Trial to Evaluate the safety and performance of the Organ Care System for Heart Transplants) clinical trial for its Organ Care System, the first system that allows a new type of organ transplant, called a living organ transplant. The primary endpoint is the seven-day patient survival rate following transplant. All patients will be followed for 30 days for further data. Long-term patient survival and other outcome measures will be tracked through established registries. TransMedics’ Organ Care System maintains organs in a functioning state outside the human body, allowing real time clinical evaluation. Warm, oxygenated, nutrient-rich blood is perfused through the organ from the time of removal until it is implanted. Maintaining the heart in a warm, functioning state until implantation may allow the organ to withstand longer periods of time outside of the body and be less vulnerable to damage during transportation to the recipient, the company said.

• VisualSonics (Toronto), a developer of high-resolution, ultrasound-based micro-imaging systems, reported at the American College of Cardiology conference in Atlanta new cardiovascular functionalities for its Vevo 770 system. The Vevo’s new Tissue Doppler Imaging feature allows quantitative myocardial analysis to be performed and used for regional myocardial strain rate. The new integrated blood pressure analysis functionality allows the Vevo 770 system to integrate a blood pressure signal from a third-party continuous pressure monitoring system. Other new features include the automated left ventricular functional analysis, which provides semi-automated continuous tracing of the chamber walls in the left ventricle in either B- or M-Mode. In addition, the Vevo software automatically generates standard left ventricular measurements and calculations derived from the traced contours and collected physiological data.

• X-Cell Medical (Princeton, New Jersey), developer of a drug-eluting stent system that uses a different class of drug than its competitors, reported in early March initiating enrollment in its multinational clinical trial to study the safety and effectiveness of the ETHOS (EsTradiol eluting stents in Humans for restenOSis) II coronary stent system. The Ethos II DES is coated with a second-generation formulation of 17(beta)-estradiol, a drug that is already approved for use in hormone replacement therapy and other indications. The ETHOS II trial is complementary to the company’s ongoing ETHOS I trial, with full six-month follow-up data to be reported sometime in the second half of 2006. President and CEO Oded Ben-Joseph, PhD, said X-Cell is confident that its drug ultimately will be a better choice for DES devices than drugs such as sirolimus, a rapamycin derivative used in Cordis’ (Miami Lakes, Florida) Cypher, and paclitaxel, used on Boston Scientific’s (Natick, Massachusetts) Taxus stents. “The reason that we are such great believers and so excited in ETHOS II is that we created a dosing and release kinetics profile which are tailor made to measure for estradiol specifically,” Ben-Joseph told CDU. He noted that estradiol is “very different” from rapamycin and paclitaxel, which he said are utilized by a process of diffusion. In contrast, he said estradiol has a “receptive mediated effect.” Estrogens are known to inhibit smooth muscle cell proliferation and to accelerate endothelial regeneration, suggesting that estrogen coated stents may reduce restenosis in human coronary arteries. This was previously demonstrated in the 30-patient EASTER registry trial, using a non-optimized drug delivery system. The ETHOS II study will include 35 patients with diagnosed stable and unstable angina or documented silent ischemia, with angiographic and intravascular ultrasound follow-up at six months to measure the percentage of in-stent volume obstruction. The data from ETHOS II will be compared with the 95-patient ETHOS I trial, which also includes a bare-metal stent, for the elimination of restenosis in patients eligible for balloon angioplasty with symptomatic ischemic heart disease due to discrete de novo and/or restenotic coronary artery lesions.