Antibacterial Envelope to Prevent Cardiac Implantable Device Infection

N Engl J Med. 2019 May 16;380(20):1895-1905. doi: 10.1056/NEJMoa1901111. Epub 2019 Mar 17.


Background: Infections after placement of cardiac implantable electronic devices (CIEDs) are associated with substantial morbidity and mortality. There is limited evidence on prophylactic strategies, other than the use of preoperative antibiotics, to prevent such infections.

Methods: We conducted a randomized, controlled clinical trial to assess the safety and efficacy of an absorbable, antibiotic-eluting envelope in reducing the incidence of infection associated with CIED implantations. Patients who were undergoing a CIED pocket revision, generator replacement, or system upgrade or an initial implantation of a cardiac resynchronization therapy defibrillator were randomly assigned, in a 1:1 ratio, to receive the envelope or not. Standard-of-care strategies to prevent infection were used in all patients. The primary end point was infection resulting in system extraction or revision, long-term antibiotic therapy with infection recurrence, or death, within 12 months after the CIED implantation procedure. The secondary end point for safety was procedure-related or system-related complications within 12 months.

Results: A total of 6983 patients underwent randomization: 3495 to the envelope group and 3488 to the control group. The primary end point occurred in 25 patients in the envelope group and 42 patients in the control group (12-month Kaplan-Meier estimated event rate, 0.7% and 1.2%, respectively; hazard ratio, 0.60; 95% confidence interval [CI], 0.36 to 0.98; P = 0.04). The safety end point occurred in 201 patients in the envelope group and 236 patients in the control group (12-month Kaplan-Meier estimated event rate, 6.0% and 6.9%, respectively; hazard ratio, 0.87; 95% CI, 0.72 to 1.06; P<0.001 for noninferiority). The mean (±SD) duration of follow-up was 20.7±8.5 months. Major CIED-related infections through the entire follow-up period occurred in 32 patients in the envelope group and 51 patients in the control group (hazard ratio, 0.63; 95% CI, 0.40 to 0.98).

Conclusions: Adjunctive use of an antibacterial envelope resulted in a significantly lower incidence of major CIED infections than standard-of-care infection-prevention strategies alone, without a higher incidence of complications. (Funded by Medtronic; WRAP-IT number, NCT02277990.).

Publication types

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

MeSH terms

  • Aged
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / adverse effects
  • Antibiotic Prophylaxis*
  • Bacterial Infections / epidemiology
  • Bacterial Infections / mortality
  • Bacterial Infections / prevention & control*
  • Defibrillators, Implantable / adverse effects*
  • Female
  • Heart Diseases / therapy*
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Minocycline / administration & dosage*
  • Minocycline / adverse effects
  • Pacemaker, Artificial / adverse effects*
  • Prosthesis-Related Infections / epidemiology
  • Prosthesis-Related Infections / mortality
  • Prosthesis-Related Infections / prevention & control*
  • Rifampin / administration & dosage*
  • Rifampin / adverse effects
  • Single-Blind Method
  • Standard of Care


  • Anti-Bacterial Agents
  • Minocycline
  • Rifampin

Associated data