New Clinical Trial Shows Medtronic TYRX™ Envelope Signficantly Reduces Major Infections in Cardiac Implantable Device Patients
Medtronic plc announced results from the landmark Worldwide Randomized Antibiotic Envelope Infection Prevention Trial (WRAP-IT), which demonstrated the TYRX™ Absorbable Antibacterial Envelope (TYRX envelope) reduced the risk of major infection by 40 percent, and pocket infection by 61 percent, in patients with cardiac implantable electronic devices (CIEDs), compared to standard-of-care pre-operative antibiotics.
The trial results were presented in a late-breaking session at the European Heart Rhythm Association Annual Congress by Bruce Wilkoff, MD, director of cardiac pacing and tachyarrhythmia devices at Cleveland Clinic, Cleveland, Ohio, as well as presented at the American College of Cardiology's 68th Annual Scientific Sessions, and published in The New England Journal of Medicine.
"CIED infections are associated with significant morbidity, mortality, and cost. Until now, in addition to adhering to strict surgical techniques, only one intervention, pre-operative antibiotics, has been shown to significantly reduce infections," said Khaldoun Tarakji, MD, MPH, associate section head of cardiac electrophysiology at Cleveland Clinic, principal investigator of the trial, and a paid consultant to Medtronic. "This study shows that, in addition to pre-operative antibiotics, the use of the antibacterial envelope significantly reduced the risk of CIED infections, and with no increased risk of complications."
The trial met its primary endpoint showing effectiveness of the TYRX envelope in reducing major infections by 40 percent in patients at increased risk for infections resulting from CIED implantation: at 12 months, 1.2 percent of patients in the control group experienced a major infection, while only 0.7 percent of patients who received the TYRX envelope had a major infection (p=0.04). The trial also showed a 61 percent reduction in pocket infections with the envelope (p<0.01).
The TYRX envelope was successfully implanted in 99.7 percent of procedure attempts, with no significant difference in procedure time between the two groups. The trial also met its safety objective: the envelope did not increase the risk of procedure-related or system-related complications through 12 months (p<0.001 for non-inferiority).
"These data provide strong evidence that the TYRX envelope can help prevent major infection without increasing complications," said Rob Kowal, MD, PhD, vice president and chief medical officer of the Cardiac Rhythm and Heart Failure division, which is part of the Cardiac and Vascular Group at Medtronic. "This is the largest CIED trial ever conducted globally, demonstrating Medtronic's commitment to generating high-quality evidence supporting the use of our products and therapies to improve patient outcomes."
WRAP-IT is a randomized, prospective, multicenter, single-blinded, global, post-market, interventional clinical trial. It compared the incidence of major infections in patients whose CIED implantation included the TYRX envelope and patients whose procedure did not, with follow-up to 12 months. The study was conducted in 181 centers in 25 countries in North America, Europe, Asia and South America, and included 776 implanters. A total of 6,983 patients participated in the trial with 3,495 randomized to receive the TYRX envelope and 3,488 randomized to the control group (without the envelope).
Millions of people with heart conditions receive a CIED, such as a pacemaker or implantable cardioverter defibrillator (ICD), to help manage abnormal heart rhythms. As with any surgical procedure, there is risk for infection due to bacteria being introduced at the time of implant. These infections occur in 1-4 percent of all patients with CIED implants,1,2 leading to an increased risk of death and an average cost per infection of $44,000-$83,000.3-7
The TYRX Absorbable Antibacterial Envelope is a mesh envelope that holds an implantable cardiac device. It is designed to stabilize the device after implantation while releasing antimicrobial agents, minocycline and rifampin, over a minimum of seven days.8 The envelope is fully absorbed by the body approximately nine weeks after implantation.8,9 The TYRX Envelope was cleared by the FDA in 2013 and received CE Mark in 2014.
In collaboration with leading clinicians, researchers and scientists worldwide, Medtronic offers the broadest range of innovative medical technology for the interventional and surgical treatment of cardiovascular disease and cardiac arrhythmias. Medtronic strives to offer products and services of the highest quality that deliver clinical and economic value to healthcare consumers and providers around the world.
Medtronic plc (www.medtronic.com), headquartered in Dublin, Ireland, is among the world's largest medical technology, services and solutions companies - alleviating pain, restoring health and extending life for millions of people around the world. Medtronic employs more than 86,000 people worldwide, serving physicians, hospitals and patients in more than 150 countries. The company is focused on collaborating with stakeholders around the world to take healthcare Further, Together.
1 Tarakji KG, et al. Am Heart J. 2016;180:12.
2 Data on file for aggregated infection rate.
3 Sohail MR, et al. Circ Arrhythm Electrophysiol. 2016;9:e003929.
4 Greenspon AJ, et al. Pacing Clin Electrophysiol. 2018;41:495-503.
5 2012 Premier Healthcare Database, data on file with Medtronic plc.
6 2014-15 Medicare 100% Standard Analytic File (SAF), data on file with Medtronic plc.
7 CPI 2016 Detailed Report: CPI1612. Assessed March 2018.
8 Huntingdon Life Sciences Study TR-2013-001.
9 Sinclair Labs Study D13599.
Hot and Cold: Major New Multicenter Trial Compares Approaches to Treating a Common Heart Condition
Late-breaking results of a major trial testing atrial fibrillation treatments were presented at the European Heart Rhythm Association Congress by Vancouver Coastal Health Research Institute scientist Dr. Jason Andrade.
AFib is the most common irregular heart rhythm condition, affecting approximately 350,000 Canadians. One-third of all strokes after age 60 are caused by AFib, and for many patients, AFib remains uncontrolled despite drug therapy. With funding support from the Heart and Stroke Foundation, Andrade’s team set out to evaluate current non-surgical catheter-based interventions.
In the multicenter trial of more than 340 patients led out of Vancouver General Hospital, Andrade focused his research on advanced generation cardiac ablation procedures. Ablation procedures attempt to remove faulty electric pathways in heart tissue that cause the abnormal electrical signals of arrhythmia. Administered by catheters inserted via the veins in the groin, the procedures Andrade studied used either heat (radiofrequency) or extreme cold (cryoenergy) to target the problematic tissue with the aim of curing the AFib.
While Andrade says trends favored cryoenergy as being safer and more effective, his study aimed to provide a definitive answer. “The interesting finding was there was no difference between cryotherapy and radiofrequency energy in terms of the long-term success. Both procedures were extremely effective at treating AFib.”
Andrade says follow-up at 12 months post-procedure showed 79 percent of patients were free of symptomatic arrhythmia. Moreover, the median amount of AFib patients experienced decreased by 99 percent compared to the period prior to ablation.
As a next step, Andrade will be examining how these treatments impacted the arrhythmia related symptoms and the patients’ quality of life. In addition, the team will examine how these arrhythmia treatments impact health care usage due to arrhythmia-related emergency room visits and hospitalization.
Because the patients in the trial have already been implanted with a tiny monitor to detect arrhythmia, it will be easy to definitively evaluate the effectiveness of the different approaches. Having the monitors in place also allows for longer-term follow-up.
Beyond comparing heat and cold, Andrade’s team went further, and looked at differences in the duration of cryoablation. The current standard is to freeze the heart tissue for 4 minutes at a time. Andrade says they wanted to know if a shorter duration has the same impact. “Based on our knowledge of how freezing affects living tissue, we hypothesized shortening the freezing durations to 2 minutes from 4 minutes would result in a comparable effectiveness, while simultaneously shortening the procedure duration. This was exactly what we found.”
Late-Breaking Clinical Trial Highlights Positive Safety and Efficacy Data for the LUMINIZE™ RF Balloon Catheter
Boston Scientific Corporation announced data from the AF-FICIENT I study during a late-breaking clinical trial session at EHRA 2019, the annual congress of the European Heart Rhythm Association in Lisbon, Portugal. The data demonstrated positive safety and efficacy results with the LUMINIZE™ Radiofrequency (RF) Balloon Catheter for isolation of pulmonary veins (PV) when treating patients with AFib.
Patients with arrhythmias such as AFib are often treated with antiarrhythmic drugs as well as cardiac ablation. The LUMINIZE RF Balloon Catheter uses RF energy to isolate the areas of the heart muscle responsible for the abnormal heart rhythm. The single-shot catheter also features built-in digital cameras for visual guidance, sensing electrodes on the balloon to assess real-time vein isolation and customizable ablation electrodes with the ability to deliver tailored levels of energy around the circumference of the balloon.
The global AF-FICIENT I study examined acute procedural success and safety for the single-shot LUMINIZE RF Balloon Catheter in two phases. Phase one tested the original design of the device and phase two included changes to enhance maneuverability and add dedicated pacing and sensing electrodes. Phase one study data showed PV isolation was achieved in 88.9% of veins. In phase two, with the enhanced steering capability and electrodes activated, PV isolation increased to 99.4% of veins. Additionally, the median time the balloon was in the left atrium — known as balloon dwell time — decreased from 92 minutes in phase one to 29 minutes in phase two, bringing the total procedure time down to a median 71 minutes.
"The study assessed the safety and effectiveness of isolating PVs through the combined benefits of RF and balloon-based ablation, both of which are found in the LUMINIZE RF Balloon Catheter," said Amin Al-Ahmad, MD, principal investigator and cardiac electrophysiologist at Texas Cardiac Arrhythmia Institute in Austin, Texas. "The data underscore the potential for this catheter to improve procedural efficacy and patient outcomes."
The prospective, non-randomized, multicenter study enrolled 100 patients with symptoms of paroxysmal — or intermittent — AFib. Confirmation of PV isolation was completed with the RF balloon sensing electrodes, a circular mapping catheter, or both. There were no device-related serious adverse events in either phase of the trial, 30 days after the completion of the procedures.
"We are pleased with the data presented today as it highlights the potential benefits of the LUMINIZE RF Balloon Catheter," said Kenneth Stein, MD, senior vice president and chief medical officer, Rhythm Management and Global Health Policy, Boston Scientific. "By providing real-time visualization both before and during ablation and individualized control of electrode energy levels, this technology may allow physicians to swiftly and accurately isolate veins and decrease procedure times."
Boston Scientific offers innovative EP products and services for the diagnosis and management of cardiac rhythm disorders. The company continues to expand its EP offerings through internal investments and acquisitions, including the purchase of a single-shot cryoablation platform for the treatment of AFib. The addition of the cryoballoon platform will position the company as the first to have both cryothermal and RF single-shot, balloon-based ablation therapies in its portfolio.
The LUMINIZE RF Balloon Catheter and the cryoballoon platform are in development, pending CE Mark and are not available for use or sale.
For more information on all product offerings within the Boston Scientific electrophysiology portfolio, visit www.bostonscientific.com/rhythmia.
About Boston Scientific
Boston Scientific (bostonscientific.com) transforms lives through innovative medical solutions that improve the health of patients around the world. As a global medical technology leader for 40 years, we advance science for life by providing a broad range of high performance solutions that address unmet patient needs and reduce the cost of healthcare.
“Back to Basics” Atrial Fibrillation Procedure Could Slash Waiting Lists
A day case catheter ablation procedure which includes only the bare essentials and delivers the same outcomes could slash waiting lists for atrial fibrillation patients, according to late-breaking results from the AVATAR-AF trial presented at EHRA 2019, a European Society of Cardiology (ESC) congress. With the simplified protocol, 30% more patients could receive catheter ablation for the same cost.
AFib is the most common heart rhythm disorder. It causes 20-30% of all strokes and increases the risk of dying prematurely.1 Symptoms include palpitations, shortness of breath, tiredness, and difficulty exercising. Catheter ablation, aimed at burning or freezing heart tissue causing AFib, is recommended to restore normal rhythm after failure of, or intolerance to, drug treatment.
Principal investigator Professor Prapa Kanagaratnam, of Imperial College London, UK, said: “Catheter ablation started in 1998. There has been little improvement in clinical outcomes in the last ten years despite costlier technologies and a more complicated procedure requiring highly skilled staff. In this trial, we stripped the procedure back to the bare essentials to see if it achieved the same outcomes.”
The AVATAR protocol eliminates electrical mapping of the pulmonary veins, thereby removing the need for pulmonary vein catheters, electrical recording equipment, and staff trained to use the equipment.
The trial enrolled 321 patients with AFib needing symptom control. Patients were randomly allocated to one of three treatments: 1) AVATAR protocol with cryoballoon ablation and discharge home the same day; 2) antiarrhythmic drugs; 3) conventional cryoballoon ablation with pulmonary vein mapping, and overnight hospitalization.
For all patients, there was a 12-week treatment period during which procedures were done and drugs were optimized. The primary endpoint was whether patients needed to attend hospital again after that period.
At one year, 21% of patients in the AVATAR group needed hospital treatment to relieve symptoms. This was significantly lower than in the drug therapy group, of whom 76% needed therapy (p<0.0001), and not significantly different to the conventional ablation group, of whom 18% required treatment (p=0.6).
“Some of the more technical parts of the procedure can be omitted, making it easier, cheaper and quicker, without sacrificing results,” said Professor Kanagaratnam. “In the UK, patients with AFib have to wait months for catheter ablation. The simpler protocol could shorten waiting lists within the same budget.”
“Eight in ten patients didn’t need to see their specialist again,” he continued. “Currently we medicalize patients with regular monitoring, but the study shows that long-term follow-up is unnecessary. Patients can contact the hospital if they have symptoms.”
The study gives the first direct proof that ablation is better than drugs for controlling symptoms and avoiding hospital treatment. “The findings also question the value of drug therapy, and whether catheter ablation should be the first line treatment for atrial fibrillation patients with symptoms,” said Professor Kanagaratnam.
Sources of funding: British Heart Foundation, Medtronic, National Institute for Health Research.
1 Kirchhof P, Benussi S, Kotecha D, et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37:2893–2962.
About the European Heart Rhythm Association
The European Heart Rhythm Association (EHRA) is a branch of the European Society of Cardiology (ESC). Its aim is improving the quality of life and reducing sudden cardiac death by limiting the impact of heart rhythm disturbances. EHRA ensures the dissemination of knowledge and standard setting; provides continuous education, training and certification to physicians and allied professionals involved in the field of cardiac arrhythmias with a special focus on AFib and EP. EHRA releases international consensus documents and position papers, it is a source of high quality, unbiased, evidence based, scientific information that promotes the quality of care for patients with AF, and for, has also dedicated a website for patients (afibmatters.org).
About the EHRA Congress
EHRA 2019 is the annual congress of the European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).
About the European Society of Cardiology
The European Society of Cardiology brings together health care professionals from more than 150 countries, working to advance cardiovascular medicine and help people lead longer, healthier lives.