The results of the first large-scale clinical study of Medtronic's (Minneapolis, Minnesota) InSync pacing device for cardiac resynchronization, reported at last month's American College of Cardiology (ACC; Bethesda, Maryland) conference, "should bring hope to thousands of patients whose quality of life has been severely affected by heart failure," said the trial's principal investigator.
William Abraham, MD, chief of the division of cardiovascular medicine at the University of Kentucky College of Medicine (Lexington, Kentucky), reported six-month results of the MIRACLE (Multicenter InSync Randomized Clinical Evaluation) trial in which 266 patients were implanted with the InSync atrial synchronous biventricular pacing device at 44 U.S. and Canadian centers.
Abraham described the results as "markedly positive," citing an implant success rate of 93%. He said the safety of the InSync Model 8040 device, the Attain LV and Attain CS pacing leads and the Model 9880 E software system "exceeded all pre-specified levels of performance." The InSync device "produced marked benefits in heart failure patients," he said, including quality of life gains and "at least one class of improvement" in the New York Heart Association (NYHA) measurement system. Using NYHA measurements, 69% of those implanted improved at least one class.
"This treatment is safe and well-tolerated, and these patients showed impressive quality-of-life gains," Abraham told an news conference prior to his more detailed study presentation as part of an ACC "Late-Breaking Clinical Trials" session. The InSync "further improves cardiac structure and function and improves heart failure composite response," he added. He said the InSync therapy could be of help to an estimated 750,000 to 1.25 million heart failure patients in the U.S. alone, adding that "cardiac resynchronization therapy may allow many patients who are not helped by drugs alone to resume many of their normal activities."
In the study, 134 patients were randomized to the treatment group, 132 to the control group. At the time of Abraham's report, 244 had completed six-month follow-up. In answer to a question, Abraham said that the patients from the control group "universally chose to have their implanted devices turned on" at the end of the six-month study period. Asked if the resynchronization device caused any degradation of heart function, he noted that the first patient in the study, implanted with the InSync device in November 1998, "is still doing well." He said researchers "haven't seen any long-term deleterious effects from the pacing."
He said that Medtronic has not yet set the price of the device in the U.S. but noted that the price "is likely to be at about the level of a high-end, dual-chamber pacemaker – about $10,000 to $12,000."
Barry Massie, MD, of the University of California, San Francisco, and the San Francisco Veterans Affairs Medical Center, who moderated the clinical trials session, said the heart failure sector "is an area of great progress and one where there is a great need for such progress." He called Abraham's study "the most unique of these papers."
In a company statement, Medtronic Chairman and CEO William George said the MIRACLE trial results "herald the beginning of a new era in device-based therapies designed to treat advanced heart failure." He said that "an entirely new patient population," those who in the past "could be managed only with drugs or through major surgical intervention, now may benefit from the InSync treatment."
The InSync and InSync ICD systems are being sold in Europe, and Medtronic has filed a premarket approval application with the FDA.
Elsewhere in the product pipeline:
Abbott Laboratories (Abbott Park, Illinois) said that preliminary data from an animal study conducted at the Mayo Clinic (Rochester, Minnesota) indicate that treatment with stents coated with an Abbott proprietary drug resulted in dramatic improvement in vessel openness vs. stents alone in a well-accepted coronary injury model in pigs. The study demonstrated that drug-coated stents lead to a 43% reduction in new tissue growth, with related improvement in internal vessel size and no significant injury or inflammation within the treated artery. The study suggests that when used in humans, drug-coated stents may significantly improve outcomes for patients with coronary artery disease (CAD), one of the leading causes of death in the U.S. "We're encouraged by the implications [of the data] for use in humans," said Edward Ogunro, PhD, vice president of hospital products research and development, medical and regulatory affairs. He said the company will conduct more studies, "which will enable us to move rapidly into human clinical trials." Abbott said drug-coated stents are the next step in angioplasty technology and could potentially lead to more effective treatment of CAD by improving care and reducing restenosis rates. The company's vascular medicine business includes both medical devices and therapeutics, and it said the combination of devices and drugs "plays a critical role in serving this market." The study tested the effects of coronary stents coated with a proprietary drug vs. stents without drug in preventing neointimal formation in the coronary arteries of 20 pigs. After 28 days, the drug-coated stents showed a dramatic improvement in reduction in neointima, as well as improvement in artery size. In addition, only mild inflammation was found with both the drug-coated stents and stents alone, indicating biocompatibility with both products.
Avant Immunotherapeutics (Needham, Massachusetts) said last month that it was making protocol changes to the Phase Iib trials of its lead complement inhibitor, TP10, after discussions with the FDA. Avant agreed to monitor 40 to 70 infants who undergo cardiac surgery using cardiopulmonary bypass for six months following treatment, as well as the previously planned 60-day follow-up. The change will result in longer trials, with completion of the Phase IIb trial now expected in 1H02. Avant said a pivotal Phase III trial in this high-risk patient population would start after meetings with the FDA after the Phase IIb trials end. The company said the ongoing Phase II study of TP10 in adults undergoing cardiac surgery remains on track and that these protocol changes only affect the pediatric trials.
Boston Scientific (Natick, Massachusetts) said that the Filterwire EX embolic protection device has received the CE mark for coronary and saphenous vein graft (SVG) applications. It received the CE mark for use in the peripheral circulatory system last October. The Filterwire EX is designed to reduce complications in angioplasty and vascular interventions. It captures embolic material that is dislodged during cardiovascular interventions. The system is manufactured by Embolic Protection (EPI; Campbell, California), acquired recently by Boston Scientific. In support of this CE mark, EPI completed a 40-patient clinical study – involving coronary and SVG patients – to evaluate the Filterwire EX's safety and efficacy. The study reported positive results.
Cambridge Heart (Bedford, Massachusetts) said that the American Medical Association (AMA; Chicago, Illinois) has notified the company that it will establish a permanent Category I CPT code for Microvolt T-Wave Alternans testing. The decision to issue the Category I code supersedes the AMA's earlier decision to issue a temporary CPT III tracking code for the procedure. The AMA determined at its February committee meeting that a new Category I CPT code is appropriate for Microvolt T-Wave Alternans testing based on literature and data submitted by Cambridge Heart. The AMA found that the data demonstrate the test is predictive of sudden death. The new code is due for publication in January 2002.
Cardiac Science (Irvine, California) said it has received FDA approval to market its Powerheart defibrillator-monitor for out-of-hospital use in the U.S. "This clears the way for Cardiac Science to significantly expand its U.S. market opportunity for Powerheart beyond hospitals to include various outpatient facilities," said Raymond Cohen, president and CEO. "Physicians now will have the opportunity to attach Powerheart to patients undergoing outpatient or office-based surgical procedures who are deemed to be at risk for developing cardiac arrhythmias." The Powerheart AECD is a noninvasive external defibrillator designed to be attached to monitors of cardiac patients for detection of life-threatening heart rhythms. If a person suffers cardiac arrest, Powerheart delivers a defibrillation shock within seconds, and without human intervention, to restore a normal heart rhythm. Cardiac Science said it has added eight direct salespeople to sell to the out-of-hospital market. Additionally, the company has been granted approval by Health Canada to allow Cardiac Science to begin marketing the Powerheart in that country.
Cook (Bloomington, Indiana) said it is the first company to receive FDA approval to evaluate a coronary stent coated with the anti-restenosis drug paclitaxel in U.S. patients. The company is conducting multicenter trials of paclitaxel-coated coronary stents in human patients in Europe and Asia. The Logic Coronary Stent from Cook uses the drug paclitaxel to inhibit restenosis. The metal body of the stent is coated with a minute quantity of the drug, which is gradually released into the cells of the arterial wall. Paclitaxel acts to prevent excessive cell regrowth at the site of the angioplasty, which researchers hope will reduce or eliminate restenosis. The stent is indicated for use in patients with symptomatic ischemic heart disease, or with a positive cardiac stress test, due to de novo lesions in native coronary arteries with a reference vessel diameter in the range of 3.0 mm to 4.0 mm. It is an investigational device not yet approved for sale in the U.S.
Cholestech (Hayward, California) said the European Patent Office has granted a patent for the company's high density lipoprotein (HDL) cholesterol assay for use on the Cholestech LDX. The grant gives Cholestech patent rights in Austria, Belgium, Switzerland, Germany, France, Spain, Great Britain, Italy, Luxembourg and the Netherlands. The HDL cholesterol test measures the amount of "good" cholesterol in the blood of a patient. This test, when combined with the other tests in a lipid profile, helps determine the ratio of HDL to low density lipoprotein (LDL) cholesterol, the so-called "bad" cholesterol. HDL/LDL ratios can be used to help determine an individual's risk of coronary heart disease. Cholestech says its system can conduct multiple simultaneous diagnostic tests from a single drop of blood and provide results, in less than five minutes, that are as accurate as similar tests performed in clinical and hospital labs.
CryoCath Technologies (Kirkland, Quebec), a maker of cryotherapy products to treat cardiovascular disease, said the FDA has conditionally approved its application to initiate a multicenter investigational device exemption study to treat supraventricular tachycardia. Enrollment of the first 165 patients in the U.S. was expected to begin before the end of March, with completion targeted before year-end. Patients will undergo a minimally invasive cryocatheter procedure to freeze the tissue causing the condition in the heart. The company said initiation of the Freezor trial of Supraventricular Tachycardia (FROSTY) puts it on schedule for premarket approval filing and subsequent sales.
Edwards Lifesciences (Irvine, California) reported FDA clearance of the Edwards Prima Plus Stentless Bioprosthesis. The Prima Plus porcine tissue valve is a next-generation treatment for surgeons who prefer a stentless alternative for replacement of a patient's diseased or malfunctioning aortic heart valve. The Prima Plus is a biograft featuring a patented trim guide that aids the surgeon in tailoring the valve for sub-coronary implantation. Based on current clinical data, Edwards' stentless valve has demonstrated excellent durability, with blood flow that is characteristic of stentless valves.
Endovasc (Montgomery, Texas) said results from a safety study of Liprostin in porcine hearts indicated the compound was safe in treating restenosis. The study indicated Liprostin administered using single bolus of up to 2.5 mg at the time of angioplasty in models having blocked arteries produced a safe treatment of restenosis, with only an 8% rate of restenosis at 28 days after treatment. The company said it will progress into Phase II and Phase III trials as a result of the testing. Endovasc also reported completing dog studies of its nicotine receptor agonist. The company said the positive results of the testing support advancing the research into the use of the nicotine receptor agonist as an angiogenic agent in ischemic pig models. That study is expected to be completed by mid-May. The company said it is continuing studies into the nicotine receptor agonist as a nonsurgical angiogenic therapy for blocked arteries to the heart.
Gemini Genomics (Cambridge, United Kingdom), a clinical genomics company, has been issued U.S. patent No. 6,156,510 for its method of diagnosing a predisposition to hypertension or sustained high blood pressure. The patent covers methods of detecting mutations in a glucocorticoid receptor gene. The company said diagnostic tests based on this patent will enable the early detection of those at risk allowing physicians to recommend treatments that will minimize the consequences of high blood pressure disease, such as stroke, kidney disease, and cardiovascular disease. Gemini is seeking commercial partners to develop and market a diagnostic kit.
Imatron (South San Francisco, California) discussed the results of a company study at an American Heart Association (Dallas, Texas) conference on cardiovascular disease epidemiology and prevention. Dr. Jerel Zoltick from the Walter Reed Army Medical Center (Washington) performed a study which determined that the electron beam tomography (EBT) coronary artery scan – Imatron's proprietary scanning technology – clearly defined a subgroup of seemingly healthy patients at high-risk for coronary artery disease (CAD) that was not identified by standard CAD risk factors. The EBT coronary artery scan was able to identify people at high risk of a heart attack or other cardiovascular event even though they were fit, athletic, healthy, did not smoke and were free of diabetes, hypertension and high cholesterol. Zoltick's study group consisted of a large group of 436 asymptomatic senior military officers (400 males, 36 females) whose ages ranged from 33 to 56 years. In addition to receiving an EBT coronary artery scan, this relatively young study group also underwent extensive cardiovascular and fitness assessments, including exercise treadmill testing, a resting electrocardiogram, medical fitness and nutritional histories, blood lipid profiles and fasting blood sugar measurements.
The nation's first robotically assisted thoracic surgery using the da Vinci surgical system from Intuitive Surgical (Mountain View, California) was performed last month at Henrico Doctors' Hospital (Richmond, Virginia). The system allows cardiac surgeons to perform minimally invasive thoroscopic procedures. In the Richman procedure conducted by Dr. Marc Katz, the internal mammary artery (IMA) was harvested for use in a coronary bypass. Using the da Vinci system, three small ports were placed in the side of the patient's chest, each no more than 1 cm in diameter. Using an endoscope and two surgical instruments, the IMA was harvested for use in the surgery. "This is the first step toward our goal of total endoscopic coronary artery bypass surgery," Katz said. The da Vinci system already is being used in Europe to perform minimally invasive stopped-heart and beating-heart bypass surgery. Hospital stays are reduced to three days, as opposed to a week-length stay in an open-heart procedure.
Medtronic Physio-Control (Redmond, Washington) has received FDA clearance for new features for the Lifepak 12 external defibrillator/monitor. The therapeutic and diagnostic Lifepak 12 product, used by trained emergency responders and medical personnel, now will offer two new trending capabilities as well as invasive pressure monitoring. The new monitoring capabilities, coupled with defibrillation therapy, will allow caregivers to carry a single device, instead of a separate defibrillator and a multi-parameter monitor during transport of critical care patients. The company says that trending of vital signs such as heart rate, respiration and blood pressure over time produces a record to aid in therapeutic decisions and in evaluating the patient's response to drug treatment. The system may be customized to the buyer's specifications, with choices of biphasic and monophasic fibrillation waveforms, automated and manual operation modes and multiple options such as noninvasive pacing, pulse oximetry, 12-lead electrocardiography, capnography and noninvasive pressure monitoring. Medtronic Physio-Control is a unit of Medtronic (Minneapolis, Minnesota).
Meridian Medical Technologies (Columbia, Maryland) reported that a new clinical study published in the European Heart Journal demonstrates the superiority of its Prime ECG electrocardiac mapping system in the early diagnosis of acute myocardial infarction in high-risk patients whose symptoms are hard to interpret with a traditional 12-lead ECG. "The value of the Prime ECG in the correct diagnosis of the cardiac condition and in the risk stratification of these patients is of paramount importance," according to an accompanying editorial by Professor Preda of Semmelweis University (Budapest, Hungary). In the study, conducted by Dr. Ian Menown and colleagues at the Royal Victoria Hospital and the University of Ulster in Northern Ireland, 54 patients with chest pain and ST depression were evaluated with a standard 12-lead ECG system as well as the Prime ECG system, which employs 80 leads placed around the patient's torso. The standard ECG evaluation correctly identified only 38% to 50% of heart attacks in these patients, while the Prime ECG detected nearly 90% of heart attacks within minutes.
PLC Systems (Franklin, Massachusetts), a maker of transmyocardial revascularization (TMR) products, said it had received CE mark approval for its next-generation CO2 Heart Laser 2. The company received FDA approval in January to market the system. Building on the clinical performance of PLC's first-generation TMR laser, the next-generation system has greater mobility due to its smaller size, said the company. The CO2 TMR therapy is a surgical procedure that is designed to improve blood flow to the myocardium of the left ventricle of the heart, which relieves chest pain in severely debilitated heart patients. A cardiac surgeon uses the laser to create about 20 to 40 channels to allow oxygen-rich blood to reach previously deprived areas of the patient's heart.
Response Biomedical (Vancouver, British Columbia) said patient testing has begun in its first multicenter clinical trial of the quantitative RAMP point-of-care diagnostic system. The results of this study are projected to be submitted to the FDA in June. Response is enrolling patients at four sites in the U.S. to evaluate the precision of the RAMP System and accuracy of the quantitative myoglobin blood test in patients suspected of having had a heart attack. RAMP tests for two additional, widely used cardiac markers, CK-MB and troponin I, are in development and expected to enter clinical trials later this year. The RAMP test menu will be expanded into areas such as critical care, cancer, infectious disease and therapeutic drug monitoring. Response also will develop a test for ischemia as part of its collaboration with Ischemia Technologies (Denver, Colorado).
Sulzer Medica (Winterthur, Switzerland) said its subsidiary, Sulzer IntraTherapeutics, a maker of medical devices used in the treatment of peripheral vascular disease and nonvascular obstructions, launched the Protege self-expanding nitinol biliary stent in the U.S. Protege is designed to be the world's first self-expanding stent that does not shorten upon placement.