BioControl Medical Gets Nod to Begin Second Phase of the INOVATE-HF Study of its CardioFit System
BioControl Medical has announced U.S. Food and Drug Administration approval to begin the second phase of INOVATE-HF (INcrease Of VAgal TonE in Heart Failure), a global, multi-center, investigational device exemption (IDE) clinical study of the company’s CardioFit® system for heart failure. The approval, which is based on the successful completion of an initial phase involving 50 patients at 21 centers worldwide, allows unconditional study expansion of up to 200 patients at 50 U.S. centers.
Initiated in April 2011, INOVATE-HF is a prospective, randomized, controlled clinical study to determine the safety and efficacy of the CardioFit, an implantable electrical stimulation device designed to improve heart function in patients with congestive heart failure (HF). The study will evaluate the system’s potential to reduce hospitalization and death among patients with HF, while also exploring whether combined treatment with CardioFit and prescription drug therapy is more effective than drug therapy alone.1
“The FDA’s approval to expand INOVATE-HF is a wonderful validation of the excellent clinical work completed in phase one of the study,” said Ehud Cohen, PhD, chief executive officer of BioControl Medical. “We applaud the efforts of our trial investigators and coordinators, who are fundamental to driving this pioneering research, and we look forward to working with a broader group of sites across the United States in the near future.”
INOVATE-HF is designed to explore the CardioFit’s potential to help treat one of the hallmarks of HF: an imbalance in the autonomic nervous system, which regulates involuntary bodily functions including heart muscle activity. In healthy individuals, the two branches of the autonomic nervous system, called the sympathetic and the parasympathetic, work in concert to regulate the heart. At the most basic level, the sympathetic increases cardiovascular activity, while the parasympathetic decreases it. In people with HF, the balance between these two branches is disrupted, leading to added stress on the heart and progressive deterioration of cardiovascular function.
While prescription medications have been successful at treating the sympathetic branch to reduce select symptoms, there have been no treatments designed to specifically and safely target the parasympathetic branch. CardioFit was developed to activate the parasympathetic nervous system directly to reduce stress on the heart, thereby alleviating HF symptoms and reversing HF deterioration. It operates by stimulating the vagus nerve on the right side of the neck.
“INOVATE-HF is an important study that may lead to an entirely new approach for treating congestive heart failure,” said Dr. Gregory Ewald, INOVATE-HF principal investigator at Washington University School of Medicine. “We’ve long known that an early marker of HF is an imbalance in the autonomic nervous system and that this imbalance contributes to HF morbidity and mortality, but we’ve only been able to treat one side of the problem using prescription medications. If the study of the CardioFit proves successful, this may be key to understanding how to treat and prevent the progression of HF.”
INOVATE-HF will ultimately enroll up to 650 patients at up to 80 centers in the United States and Europe. Results of the INOVATE-HF study will be used to support a Premarket Approval Application (PMA) to the U.S. Food and Drug Administration (FDA) for market clearance of CardioFit.
About the CardioFit
The CardioFit system consists of a stimulator, a sensor lead and a stimulation lead, which are implanted under the skin of the chest. The sensor lead is extended from the stimulator to the right ventricle of the heart, and the stimulation lead is extended from the stimulator to the vagus nerve on the right side of the neck. Once activated, the stimulator’s electrical pulses are transferred via the stimulation lead to the vagus nerve. At the same time, the sensor lead monitors changes in heart activity and turns stimulation on or off accordingly. Like a pacemaker, the CardioFit System can be programmed on and off via external wireless communication with the device.
The safety and performance of the CardioFit have been validated in a 32-patient, multi-center, pilot clinical study conducted in Germany, Italy, The Netherlands and Serbia.2 Study data showed that patients experienced sustained significant improvement across key clinical measures including left ventricular function and structure, heart rate variability, and resting heart rate.2 Patients also showed improvement in self-reported quality of life surveys and six-minute hall walk tests.1 The results of this pilot study supported BioControl Medical’s filing for CE mark certification to market and sell CardioFit in the European Union, which it was granted in December 2008.
About BioControl Medical
Headquartered in Yehud, Israel with offices in New Hope, MN, BioControl Medical develops and markets advanced implantable devices for the treatment of autonomic disorders, conditions whereby the autonomic nervous system ceases to function properly, resulting in a disruption to the control of involuntary body processes. The devices enable controlled electrical stimulation of various nerves to achieve therapeutic results.
Caution: In the United States, the CardioFit is an investigational device. Limited by Federal (or United States) law to investigational use.
- Hauptman PJ, Schwartz PJ, Gold MR, et al. Rationale and study design of the INcrease Of Vagal TonE in Heart Failure study: INOVATE-HF. Am Heart J 2012;163:955-962.
- De Ferrari GM, Crijns HJ, Borggrefe M, et al. Chronic vagus nerve stimulation: A new and promising therapeutic approach for chronic heart failure. Eur Heart J 2011;32:847-855.
Boston Scientific Completes Patient Enrollment in PREVAIL Study for First-in-Class WATCHMAN Device
Boston Scientific Corporation has completed enrollment in the PREVAIL confirmatory study, designed to gain U.S. Food and Drug Administration (FDA) approval for the WATCHMAN® Left Atrial Appendage (LAA) Closure device. The prospective, randomized trial enrolled 407 patients at 42 sites and is comparing the WATCHMAN device to warfarin in high-risk patients with atrial fibrillation (AF) eligible for long-term warfarin therapy. Patient follow up of six months is required prior to submission to the FDA.
“WATCHMAN is the most clinically studied device of its kind,” said Vivek Reddy, MD, Director of Cardiac Arrhythmia Service at Mount Sinai Medical Center and principal investigator of the PREVAIL study. “WATCHMAN has the potential to provide atrial fibrillation patients with a safe and effective first-in-class device-based solution to reduce risk of stroke.”
The PREVAIL study began enrollment in November 2010. Patients were randomly selected to receive either the WATCHMAN device or remain on long-term warfarin therapy. Those selected to receive the WATCHMAN device remained on warfarin for 45 days following implant.
WATCHMAN has been studied in more than 2,000 patients, exceeding 4,000 patient-years of follow up. The evidence-based clinical program for WATCHMAN includes two landmark studies: the PROTECT AF trial and the ASA Plavix (ASAP) study. In the multi-center, randomized PROTECT AF trial, the WATCHMAN device proved to be non-inferior to warfarin and demonstrated a 38 percent relative risk reduction for stroke, cardiovascular death and systemic embolism compared to long-term warfarin therapy in 707 patients. Data from the prospective, multi-center ASAP study showed a 77 percent reduction of ischemic stroke risk in patients with AF implanted with the WATCHMAN device and not eligible for blood-thinning medications.
“WATCHMAN is already available in 30 countries. Enrollment completion of the PREVAIL study is a significant milestone in helping to bring this innovative therapy to patients living with atrial fibrillation in the U.S.,” said Kenneth Stein, MD, chief medical officer of Boston Scientific’s Cardiac Rhythm Management Group. “We look forward to the results of PREVAIL and the opportunity to enter the structural heart space in the U.S.”
WATCHMAN is a novel device manufactured by Boston Scientific Corporation that is introduced into the heart via a flexible tube (catheter) through a vein in the groin and closes off the LAA. The device is designed to capture any clots that may form in the appendage, reducing the risk of stroke and potentially eliminating the need for long-term use of blood-thinning medications.
Atrial fibrillation affects approximately 15 million patients worldwide and is a disorder that disrupts the ability of the heart to beat regularly and pump blood efficiently. Patients in AF are at a greater risk for stroke due to the migration of clots formed in the LAA. Blood-thinning medications have previously been the only therapy for reducing stroke risk in these patients.
The WATCHMAN device was approved for marketing in Europe and some countries in Asia in 2005. It is contraindicated in patients who are not eligible for anticoagulation therapy.
In the U.S., the WATCHMAN device is an investigational device, limited by applicable law to investigational use and not available for sale. The device was developed by Atritech, which Boston Scientific acquired in March 2011.
St. Jude Medical Announces Initial Findings from Riata Lead Evaluation Study
St. Jude Medical, Inc. announced initial findings from the Riata® Lead Evaluation Study. The study’s phase-one results found that externalized conductors occurred in 9.3 percent of the smaller-diameter Riata ST 7F leads in the study, and in 24 percent of the larger-diameter Riata 8F leads. A full summary of the phase-one study results are available on the company’s riatacommunication.com website, a dedicated resource for providing the latest information on Riata leads.
The Riata Lead Evaluation Study is an international, multi-center, prospective study of Riata and Riata ST silicone defibrillation leads. It enrolled 724 patients at 20 sites in the U.S. and Canada. An additional 51 patients were enrolled at three sites in Japan. Those results are awaiting final adjudication and will be reported at a later date.
The study will continue to evaluate the performance of Riata leads — both with and without externalized conductors — over the next two years to determine how they function over time, which may help further inform patient management considerations. In other clinical studies, the majority of leads with an externalized conductor continued to function normally.
“The rates of externalized conductors in this study are consistent with other published studies involving fluoroscopic screening of patients with Riata leads. This study also reinforces that externalized conductors are more prevalent in larger-diameter Riata leads,” said Dr. Mark Carlson, chief medical officer and senior vice president of clinical affairs for the St. Jude Medical Cardiac Rhythm Management Division. “We are now focused on collecting longer-term data in the second phase of this study. Our goal is to provide physicians timely and relevant clinical data to best support their patient management decisions.”
An experienced physician panel adjudicated fluoroscopic images using objective criteria for the presence or absence of externalized conductors in enrolled patients’ leads. The St. Jude Medical independent Leads Medical Advisory Board has reviewed the results and recommends no changes to existing patient management recommendations.
Based on an analysis of products returned to St. Jude Medical, externalized conductors in Riata leads are most frequently associated with inside-out abrasion, which occurs when the cables housed within the outer insulation of the lead work their way outside of the lead body as the result of movement against the insulation. External, or outside-in, abrasion is a known cause of failure across all cardiac leads in the industry, and is different from the inside-out abrasion seen with externalized conductors in some Riata leads.
Externalized conductors can be visualized through x-ray or fluoroscopy; however, it is important to note that externalized conductors may be visualized without any associated clinical or device-related observations. In the majority of reported cases, a lead with an externalized conductor continued to function normally.
For additional background information on Riata leads, including a pre-recorded webinar discussing these results and other patient management considerations, please visit riatacommunication.com.
eCardio Supports the Carolinas HealthCare Foundation Through Grant for Heart Of A Champion Day
eCardio Diagnostics recently awarded a grant to the Carolinas HealthCare Foundation in support of the 2012 Heart Of A Champion Day in Charlotte, NC.
The program, pioneered by Carolinas HealthCare System, is in its fifth year and is one of the largest and most comprehensive high school athlete screening programs in the United States. It provides cardiac and general athletic physical screenings to thousands of student athletes from throughout the Charlotte-Mecklenburg public school system. The value of the screenings is estimated at $1,500 per student, but provided through the program at no charge.
“We’re proud to have supported Heart Of A Champion Day for the past two years and honored to be invited to participate again,” said Larry Lawson, eCardio’s President and Chief Executive Officer. “The work of Carolinas HealthCare System reflects our shared desire to assist physicians in the diagnoses of cardiac issues as early and as thoroughly as possible.”
The screenings check for heart abnormalities that could lead to sudden death and may include an electrocardiogram and echocardiogram. Neither heart test is offered during a routine athletic screening. The three main genetic defects that doctors look for during the cardiac screening are hypertrophic cardiomyopathy, Wolff-Parkinson-White syndrome, and long QT syndrome.
Of the 1,300 screenings completed at the Carolinas Medical Center campus on June 2, one hundred students were required to have follow-up care prior to clearance for participation in athletics. Seventy-eight follow-ups were for general medical or orthopedic red flags, and 22 were directly related to cardiac concerns.
“We are honored by eCardio’s continued generous support and participation in this event. This invaluable free screening program for our area high school athletes could not be provided without the tremendous help from our sponsors and volunteers,” said Scott Kerr, Vice President for Carolinas HealthCare Foundation.
One of the day’s highlights included a visit from the Carolina Panthers’ quarterback, Cam Newton, which can be seen in a video summary of the event: http://www.youtube.com/watch?v=sBTxzoXAZGo&feature=youtu.be
eCardio Diagnostics, LLC (www.ecardio.com), is one of the nation’s leading providers of comprehensive and advanced technologies, devices, services and solutions for the diagnosis, monitoring and subsequent clinical management of cardiac arrhythmias, predominantly in an ambulatory setting. eCardio provides leading-edge diagnostic innovations and solutions that optimize the flexibility, speed and accuracy of cardiac arrhythmia diagnoses.
About The Heart Of A Champion Day
The Heart Of A Champion Day (www.heartofachampionday.org) program began as a pilot in 2006, offering 80 screenings to area student-athletes. The program, pioneered by Carolinas HealthCare System, now partners with Charlotte-Mecklenburg Schools to screen more than 1,300 student athletes in a single day, and has grown to include four Saturdays in 2012. The program is directed by Dr. Nicholas Sliz, FACC, Pediatric Cardiologist at Sanger Heart & Vascular Institute, and Dr. David Price, Associate Director of Primary Care Sports Medicine at Carolinas Medical Center.
Large-Scale BIOTRONIK SPIRIT-ICD Study Enrollment Complete
BIOTRONIK, a leading manufacturer of innovative medical technology, announced that enrollment is now complete for the much-anticipated SPIRIT-ICD study, with 503 patients from 37 sites in 11 countries worldwide registered.
The SPIRIT-ICD study was initiated based on findings from the MADIT II trial, which showed that patients who received an appropriate therapy from an ICD (Implantable Cardioverter-Defibrillator) that was implanted for primary prevention had a significantly increased risk for all-cause mortality.1 SPIRIT-ICD is a prospective, uncontrolled, multi-center trial to investigate whether this high-risk group might benefit from an intensified diagnostic follow-up and timely therapeutic intervention.
Study patients will be closely monitored for at least one year after enrollment via BIOTRONIK Home Monitoring®, a globally accessible, Internet-based, automatic remote monitoring system that uniquely enables physicians to follow their patients’ clinical status and device status no matter where they are.
If an appropriate therapy (shock or antitachycardia pacing [ATP]) is delivered, the study protocol requires a hospital visit within 72 hours to undergo intensified diagnostics and, at the investigator’s discretion, to receive state-of-the-art therapeutic interventions. If an appropriate therapy is delivered during the patient’s observation period, monitoring is to be extended for an additional 12 months after the event.
“The main objective of this study,” summarized Professor Robert Hatala, principal investigator and Head of the Department of Cardiology at the National Cardiovascular Institute in Bratislava, Slovakia, “is to investigate whether early intervention can significantly reduce the hazard ratio for patients who receive an appropriate therapy compared to those who don’t. We hope that early intervention and intensified diagnostic follow-ups will reduce the hazard ratio and, ultimately, reduce the increased mortality risk in this high-risk group. Furthermore, this trial will yield important new data on the incidence of ICD therapies in a patient population treated for acute myocardial infarction and thereafter with state-of-the-art therapeutic interventions.”
Further parameters to be compared and analyzed between the groups are sudden cardiac death, nonsudden cardiac death, risk of first heart failure hospitalization, number of ventricular tachycardia (VT) storms and number of delivered ICD therapies. In addition, the large study sample of the SPIRIT-ICD study allows for conclusions to be drawn on the current standard of care as compared to the findings of the MADIT II trial. Final results of the SPIRIT-ICD study are expected in early 2015.
The MADIT II trial was the first study of its kind to examine survival benefits of ICD implantation in patients with a history of myocardial infarction and left ventricular dysfunction.
“BIOTRONIK is committed to supporting excellent research that will provide valuable clinical evidence for physicians. The SPIRIT-ICD study will enhance our body of knowledge of ICD therapy and provide valuable insights into how early intervention after an appropriate shock may be beneficial to the patient,” commented Christoph Böhmer, Managing Director, BIOTRONIK.
- Moss AJ, et al. NEJM 2002;346:877-883.
American Osteopathic Association Calls for Automated External Defibrillators in Schools
Concerned about the safety of young athletes, members of the American Osteopathic Association’s (AOA) House of Delegates voted to encourage schools to have readily accessible automated external defibrillators (AEDs).
The majority of cases of commotio cordis — a sudden cardiac event occurring after a blow to the chest — happen during youth or high school competitive sports, such as baseball or football. AEDs may help save lives while waiting for emergency personnel to arrive on the scene.
“Unfortunately, there is only a 15% survival rate from a commotio cordis event due to lack of early recognition of the severity of the problem,” says Stanley E. Grogg, DO, an AOA board-certified pediatrician and an associate dean of clinical research and a professor of pediatrics at the Oklahoma State University Center for Health Sciences College of Osteopathic Medicine in Tulsa. “The accessibility of an automated external defibrillator at schools and sporting events can buy young athletes time until medical professionals arrive on the scene.”
Currently, 13 states, including Illinois, have legislation requiring schools to have these devices. Five states have pending legislation and three states have legislation “encouraging” schools to have an AED.
About the House of Delegates
The AOA’s House of Delegates, comprised of more than 500 delegates representing osteopathic state medical associations, specialty societies, interns, residents and students from throughout the country, meets annually in July to set organizational policies and elect new officers.
About the American Osteopathic Association
The American Osteopathic Association (AOA) proudly represents its professional family of more than 100,000 osteopathic physicians (DOs) and osteopathic medical students; promotes public health; encourages scientific research; serves as the primary certifying body for DOs; is the accrediting agency for osteopathic medical schools; and has federal authority to accredit hospitals and other health care facilities. More information on DOs/osteopathic medicine can be found at www.osteopathic.org.