What plans are held to progress the impressive findings of an envelope for cardiovascular device infection?
The global, randomized WRAP-IT—in which the TYRX antibacterial envelope was assessed in patients with cardiac implantable electronic devices (CIEDs)—showed the novel device could reduce infection risk by 40%, and could ultimately lessen a patient’s mortality due to untreated infections.
But even more, it gave clinicians a data pool of about 7000 patients showing that infection rates may not be as prevalent in CIEDs as previously thought. In an interview with MD Magazine® while at the American College of Cardiology (ACC) 2019 Annual Meeting in New Orleans, LA, this weekend, Khaldoun Tarakji, MD, MPH, an electrophysiologist in the Department of Cardiovascular Medicine at the Cleveland Clinic, discussed the WRAP-IT findings, and the research team’s plans to now assess infection risk factors.
MD Mag: What were the results of the WRAP-IT trial?
Tarakji: The WRAP-IT study was to assess the effectiveness and safety of the antibiotic envelope. In order to answer this question, we conducted the study. This was a global study, and we enrolled close to 7000 patients across the globe, 181 centers in 25 countries. And those patients were randomized in 1:1 fashion. One group got the envelope at the time of the procedure, the other group did not get the envelope, and that's our control team.
We followed this group of patients throughout 12 months of follow-up at a minimum, and the primary endpoint was major device infection over a course of 12 months in both groups, and then we made the comparison. We also assessed the secondary endpoint: the safety. The complications happened more in 1 group versus the other.
The primary endpoint showed that the envelope was effective. It led to a significant 40% relative risk reduction in the risk of major CIED infection over 12 months of follow-up, without increasing any complications. The complication rate in both groups were very similar, and the envelope use did not lead to an increase in complications.
So we have a therapy that has proven to be effective, and at the same time it's safe. What we learned in WRAP-IT was, in general, the infection rate was lower than we expected. So, in the control group, the risk of major infection over the course of 12 months was 1.2% in the control group versus 0.7% in the envelope group. And that is, for us as an electrophysiology community, that is good news. This is coming at a time when people were concerned about the rate of new infected devices outpacing the rate of newly implanted devices, and whether infections are getting out of control.
What we learned from WRAP-IT—that infection rate is on the lower side of 1.2% in the control group—that we can be able to start with a low infection rate and drop it even significantly lower to 0.7% with 40% relative risk reduction, was remarkable. And, without increasing any complications.
Are there any plans for follow-up assessment?
Sure. So, WRAP-IT is one of the largest studies conducted in the field of electrophysiology. In studies in our field, 7000 patients is a very large number. It's truly a global study. We tried our best to be as inclusive as possible. So we want this to be global. It was conducted in 25 countries across the world, and we limited the enrollment in each center to 100 patients because we want everybody to participate and not to be exclusive to certain tertiary care at high-volume centers.
We're going learn a lot from WRAP-IT. There's a lot of questions in the field of device infections that are still not answered. Let's start with a true rate of device infection in a large cohort, where they’re followed prospectively over a course of 12 months with very clear definition of what major device infection is, with a clear denominator of the whole cohort.
We had an adjudication committee that reviewed all these adverse events and consisted of both electrophysiologists and infectious disease experts in the field. And they adjudicated all the adverse events. We're going to learn more about the risk factors that accompanies infection, and there's a lot of forthcoming data involving the cost-effectiveness of using the envelope and minimizing the risk of infection. And that's hopefully coming in the near future.