Antibacterial envelope reduces rate of cardiac device infections in WRAP-IT
NEW ORLEANS — Wrapping cardiac implantable devices in an antibiotic-eluting envelope, in addition to standard infection prevention strategies, reduced the risk for major device-related infections by approximately 40%, researchers reported at the American College of Cardiology Scientific Session.
Researchers for the WRAP-IT study randomly assigned 6,983 patients undergoing a cardiac implantable electronic device (CIED) pocket revision, generator replacement or system upgrade or undergoing initial implantation of a cardiac resynchronization therapy defibrillator to a device wrapped in a bioabsorbable antibacterial envelope (Tyrx, Medtronic) or standard-of-care strategies to prevent infection.
Infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence or death occurred at a low rate of 1.2% in the standard-of-care group. However, at 0.7%, the rate was even lower in the envelope group (HR = 0.6; 95% CI, 0.36-0.98), whereas procedure-related or system-related complications were comparable in the two groups (envelope group, 6%; control group, 6.9%; P < .001 for noninferiority), Khaldoun G. Tarakji, MD, MPH, associate section head of cardiac electrophysiology at the Cleveland Clinic Heart and Vascular Institute, said during his presentation of the data.
“The results essentially show that the envelope is safe and effective and also did not increase complication rates,” he told Cardiology Today.
Effective across subgroups
For the study, Tarakji and colleagues defined infections as superficial cellulitis within the region of the pocket with at least one incidence of erosion, drainage, deep pocket infection, persistent bacteremia or endocarditis. For infections to be considered major, they had to lead to system removal, including the device and leads, or any invasive procedure, such as pocket revision or extended antibody suppressive therapy, which was mainly for patients who were not candidates for lead extraction. All other infections were classified as minor.
The researchers found that approximately 75% of major infections were pocket infections. When looking at pocket infections alone, Tarakji said, there was a 61% RR reduction in major infections with use of the envelope over 12 months.
“We followed patients for a minimum of 12 months. However, we continued to follow-up all patients through the whole follow-up duration. Again, it seems like the effect of the envelope was sustained over time, with an event rate of 1.3% in the envelope group vs. 1.9% in the control arm at 36 months,” he said during his presentation. “However, after multiple comparison adjustment, the adjusted P value was not significant for this endpoint.”
In subgroup analyses, it appears the envelope’s effects were consistent across subgroups, including age, sex, comorbidities and device type, he added.
“This study provides comprehensive data on CIED-related infection and strong evidence for the use of the envelope for infection prevention in this patient population,” Tarakji said.
The study was not without limitations, he said, including that only one manufacturer’s device was used, which may have affected the nature of enrollment.
“The envelope itself has been commercially available and that may have led to some selection bias in participation with the trial,” Tarakji said.
Patients were enrolled from 2015 to 2017. The mean age was 70 years and 28% were women. Notably, patients were excluded if they were at exceptionally high risk for infection due to special circumstances, such as patients on dialysis or those who had an infection within the previous 12 months.
Challenge of device-related infections
Major device-related infections in patients undergoing device implantation procedures, including pacemakers and implantable cardioverter defibrillators, occur in 1% to 4% of these procedures, based on prior data, according to Tarakji.
“While the rate is small, the consequences could be serious and sometimes catastrophic,” he said during his presentation. “When you have a diagnosis of device infection, the management requires removal of the device and the leads, in addition to extended antibiotic therapy and longer hospitalization. And, despite going through all of the proper management steps, estimated 30-day mortality is still about 4% to 5% and 12-month mortality can be up to 15% to 18%.”
The antibacterial envelope, which is designed to wrap around an implantable cardiac device and keep it stable in the pocket while also decreasing infection risk, is constructed of a multifilament mesh with an absorbable polymer mixed with two antibiotics — minocycline and rifampin — that are released in the pocket for 7 days, and it is fully absorbed after 9 weeks.
“In order to determine whether the envelope could reduce major device-related infection rates, we conducted a global study that included nearly 7,000 patients from 181 centers in 25 countries performed by 776 implanting physicians. We wanted to be as inclusive of all types of practices as possible,” Tarakji told Cardiology Today.
Tarakji said the electrophysiology community is excited about the WRAP-IT results because given the size of the size, it represents an opportunity to learn more about device infection in general.
“We’re going to look into all of the clinical variables that we have, in addition to all procedural characteristics, to see if we can develop models to predict which patients are likely to develop infection,” Tarakji said.
Cost is another area of concern, he added.
“With the small event rate, the cost of the envelopes is going to come up, and that’s a healthy discussion to have. It’s difficult to have a discussion about cost-effectiveness if you don’t have evidence that an intervention is actually effective and safe. So now that we know the envelope is effective and safe, it’s natural and expected to have that discussion about cost,” Tarakji said. “That’s something else that WRAP-IT will have provided us with — an opportunity to prospectively assess as accurately as we can the true cost of infection.”
For now, though, Tarakji and colleagues said they remain enthusiastic about the trial’s success.
“In other subspecialties in cardiology, mega-trials involving thousands and thousands of patients is normal, but it’s not like that for the electrophysiology community, so we’re very proud. We’re a smaller society, but this shows we can do it if we want to,” Tarakji told Cardiology Today. – by Melissa Foster with additional reporting by Darlene Dobkowski
Tarakji KG. Joint American College of Cardiology/Journal of the American Medical Association Late-Breaking Clinical Trials. Presented at: American College of Cardiology Scientific Session; March 16-18, 2019; New Orleans.
Disclosures: The study was funded by Medtronic. Tarakji reports he receives nonfinancial support from Cleveland Clinic C5 and Medtronic; personal fees from Medtronic; and personal fees from AliveCor.
Editor’s Note: This article was updated on March 19, 2019 to correct some data-related errors. The Editors regret the errors.