TYRX™ Envelope for Prevention of Infection Following Replacement With a CRT or ICD

Centurion and Citadel Studies of TYRX™ Anti-Bacterial Envelope and Custom Mesh for Prevention of Infection Following CIED Replacement With a CRT or ICD

The purpose of this study is to compare the incidence of cardiac implantable electronic device (CIED) infection and CIED mechanical complication after CIED replacement with a high-power cardiac implantable electronic device; either a cardiac resynchronization therapy device (CRT), or an implantable cardioverter defibrilator (ICD) and TYRX Anti-Bacterial Envelope (formerly known as "AIGISRx"), to the incidence, after replacement with an ICD or CRT and no TYRX.

Cardiac implantable electronic device (CIED) infection is associated with significant morbidity and expense. The frequency of CIED infection is increasing faster than the frequency of CIED implants, suggesting more effective prophylactic strategies are needed.

The TYRX Anti-Bacterial Envelope is an FDA-cleared polypropylene mesh that is intended to securely hold a pacemaker pulse generator or defibrillator (ICD) in order to create a stable environment when implanted in the body. It contains the antimicrobial agents, rifampin and minocycline, which have been shown to reduce infection in an in vivo model of bacterial contamination following surgical implant of the generator or defibrillator.

This is a prospective, observational, multicenter registry of subjects undergoing CIED replacement with an ICD or CRT and TYRX, with or without lead revision/addition. The registry subjects will be compared to a published historical control group undergoing CIED replacement with an ICD or CRT and no TYRX , with or without lead revision/addition. The CRT registry subjects will also be compared to a case-matched retrospective control group undergoing CIED replacement with a CRT and no TYRX , with or without lead revision/addition. The primary study endpoints are major CIED infection and CIED mechanical complication during the 12 months following CIED replacement with an ICD or CRT.

Originally executed as two separate studies (Citadel - ICDs) and (Centurion - CRTs), a protocol amendment was executed in 2012 due to slow enrollment, combining the databases for analysis of results.

Inclusion Criteria: - Prospective Arms

• Qualifying CIED Implant procedure was replacement with an ICD or CRT and TYRX, with or without lead revision/addition
• Received a complete TYRX Anti-Bacterial Envelope Model# 3122 or #3133 according to the Instructions for Use (IFU)
• Clinically stable to tolerate procedure
• 18 years or older
• Able to return for follow-up care through the 12-month visit, or able to have referring physician provide follow-up data to study site by telephone

Exclusion Criteria: - Prospective Arm

• Unable/unwilling to provide informed consent
• Contraindication to receiving the TYRX device, in accordance with the package labeling
• Pregnant or was at risk for becoming pregnant in the 30 day period following the Qualifying TYRX Implant
• Current CIED infection, or the indication for Qualifying CIED Implant was replacement of CIED that was explanted for infection
• Clinical diagnosis of an active infection at the time of CIED implant, including pneumonia, urinary tract infection, endovascular, cellulitis, bacteremia, or other major systemic infection. (Note: asymptomatic bacteremia without UTI is not an exclusion criterion)
• Generator replacement required planned lead extraction
• Participating in another clinical study evaluating a drug or device designed to reduce CIED infections
• Life expectancy of less than 6 months
• Expected to receive a heart transplant within 6 months
• With the exception of the elderly in good mental health, all vulnerable subjects as defined by the FDA Office of Human Research Protection or local IRB will be excluded

Inclusion Criteria: - Case-matched retrospective Control Arm

• Qualifying CIED Implant was replacement with a CRT and TYRX, with or without lead revision/addition

• First un-enrolled patient meeting case-matching criteria in series of patients implanted with a CIED and no TYRX beginning 24 months prior to the date of first TYRX implant at site. If no matching patients in this period, first un-enrolled matching patient implanted with a CIED and no TYRX beginning 24 months prior to the first TYRX implant at site, searching in reverse chronological order

• Had at least one of following by date of enrollment into the study:

  1. ≥ 12 months follow-up after Qualifying TYRX Implant
  2. Subsequent TYRX Procedure that required opening the generator pocket or implant incision ≤ 12 months after Qualifying TYRX Implant (e.g. battery change, upgrade, lead revision, explant)
  3. Death ≤ 12 months after Qualifying CIED Implant

• Survived Qualifying CIED Implant to discharge, died of a CIED infection or Mechanical Complication prior to hospital discharge, or died for any reason un-related to Qualifying CIED Implant prior to hospital discharge

• 18 years or older

Exclusion Criteria: - Case-matched retrospective Control Arm

• Contraindication to receiving the TYRX device, in accordance with the package labeling
• Pregnant or became pregnant in the 30 day period following the Qualifying TYRX Implant.
• CIED infection, or the indication for Qualifying CIED Implant was replacement of CIED that was explanted for infection
• Clinical diagnosis of an active infection at the time of Qualifying CIED Implant, including pneumonia, urinary tract infection, endovascular, cellulitis, bacteremia, or other major systemic infection (Note: asymptomatic bacteriuria without UTI is not an exclusion criterion)
• Lead extraction was performed at the Qualifying CIED Implant
• Participated in another clinical study evaluating a drug or device intended to reduce CIED infections
• Received a heart transplant within 6 months of Qualifying CIED Implant
• With the exception of the elderly in good mental health, all vulnerable subjects as defined by the FDA Office of Human Research Protection or local IRB will be excluded