The World-wide Randomized Antibiotic Envelope Infection Prevention (WRAP-IT) trial: Long-term follow-up

Heart Rhythm. 2020 Jul;17(7):1115-1122. doi: 10.1016/j.hrthm.2020.02.011. Epub 2020 Feb 19.


Background: The World-wide Randomized Antibiotic Envelope Infection Prevention trial reported a 40% reduction in major cardiac implantable electronic device (CIED) infections within 12 months of the procedure with the use of an antibacterial-eluting envelope (TYRX Absorbable Antibacterial Envelope, Medtronic, Mounds View, MN).

Objective: The purpose of this report was to describe the longer-term (>12 months) envelope effects on infection reduction and complications.

Methods: All trial patients who underwent CIED replacement, upgrade, revision, or initial cardiac resynchronization therapy - defibrillator implantation received standard-of-care infection prophylaxis and were randomized in a 1:1 ratio to receive the envelope or not. CIED infection incidence and procedure and system-related complications were characterized through all follow-up (36 months) by using Cox proportional hazards regression modeling.

Results: In total, 6800 patients received their intended randomized treatment (3371 envelope; 3429 control; mean follow-up period 21.0 ± 8.3 months). Major CIED-related infections occurred in 32 envelope patients and 51 control patients (Kaplan-Meier [KM] estimate 1.3% vs 1.9%; hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.41-0.99; P = .046). Any CIED-related infection occurred in 57 envelope patients and 84 control patients (KM estimate 2.1% vs 2.8%; HR 0.69; 95% CI 0.49-0.97; P = .030). System- or procedure-related complications occurred in 235 envelope patients and 252 control patients (KM estimate 8.0% vs 8.2%; HR 0.95; 95% CI 0.79-1.13; P < .001 for noninferiority); the most common were lead dislodgment (1.1%), device lead damage (0.5%), and implant site hematoma (0.4%). Implant site pain occurred less frequently in the envelope group (0.1% vs 0.4%; P = .067). There were no (0.0%) reports of allergic reactions to the components of the envelope (mesh, polymer, or antibiotics).

Conclusion: The effects of the TYRX envelope on the reduction of the risk of CIED infection are sustained beyond the first year postprocedure, without an increased risk of complications.

Trial registration: NCT02277990.

Keywords: Cardiac resynchronization therapy; Complication; Generator replacement; Implantable cardioverter-defibrillator; Infection; Pacemaker; Replacement.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Bacterial Agents / therapeutic use*
  • Antibiotic Prophylaxis / methods*
  • Defibrillators, Implantable / adverse effects*
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Prospective Studies
  • Prosthesis-Related Infections / epidemiology
  • Prosthesis-Related Infections / prevention & control*
  • Risk Factors
  • Single-Blind Method
  • Time Factors


  • Anti-Bacterial Agents

Associated data