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Study Summary

The randomized, controlled, multicenter Worldwide Randomized Antibiotic Envelope Prevention Trial (WRAP-IT) demonstrated that in 6983 adult patients undergoing placement of a cardiac implantable electronic device (CIED), the use of a bioabsorbable, antibiotic-eluting mesh envelope (TYRX, Medtronic) was associated with a 40% reduction in the primary end point of infections resulting in system extraction or revision, long term antibiotic therapy with infection recurrence, or death within 12 months after procedure, compared to standard of care (control arm) with pre-procedure intravenous antibiotics (0.7% vs. 1.2%, P = 0.04; see accompanying Hurst's Central Illustration). The secondary end point of procedure or system-related complications within 12 months of the procedure was not significantly different between groups (6.0% vs. 6.9%, P <0.001 for non-inferiority). Interestingly, in the subgroup of high power devices (implantable cardioverter-defibrillator or cardiac resynchronization therapy with defibrillator), envelope use was associated with a 50% reduction in the primary end point compared to standard of care (0.7% vs. 1.4%; HR 0.51, 95% CI 0.29-0.90). In the low power device subgroup (pacemaker or cardiac resynchronization therapy with pacemaker), there was no significant difference in the primary end point between the two approaches (0.9% vs. 0.8%; HR 1.02, 95% CI 0.36-2.92).

Commentary

Study Strengths: WRAP-IT introduces a safe and effective strategy for reducing the rare but serious complication of major CIED infections. Implant-related CIED infections occur in only 1-4% of cases, but are associated with prolonged hospitalization, increased treatment costs, and higher mortality. As a single-use device, the TYRX envelope delivers minocycline and rifampin over 7 days and the mesh becomes fully absorbed within 9 weeks, leaving no permanent imprint. The large international enrollment, minimal cross-over rate (2.3% in envelope group, 0.7% in control group), and extended follow-up period of 36 months supports the generalizability and durability of the findings to a broad patient population.

Study Limitations: During the 2015-2017 patient enrollment period, the TYRX envelope was commercially available, which allows for possible selection bias for enrollment. The CIEDs involved in WRAP-IT were limited to the same manufacturer as the TYRX, which prevents generalizability to other manufacturer CIEDs. Lastly, there were a higher number of immunosuppressed patients in the control group compared to the envelope group (2.4% vs. 1.4%).

Next Steps/Clinical Perspective: The envelope would likely also benefit patients with subcutaneous implantable cardioverter-defibrillators and this needs to be evaluated separately. Additionally, cost-benefit analysis and consideration of number needed to treat is required to establish the degree to which this practice will be widely adopted for CIED implants.

Trial Reference

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Tarakji  KG, Mittal  S, Kennergren  C, et al. Antibacterial envelope to prevent cardiac implantable device infection. N Engl J Med. doi: 10.1056/NEJMoa1901111

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