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

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Implantable Electronic Device Infection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 1262

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Princeton Medical Center
    • Decatur, Alabama, United States, 35601
      • Decatur General Hospital
    • Florence, Alabama, United States, 35630
      • Eliza Coffee Memorial Hospital
    • Gadsden, Alabama, United States, 35901
      • Riverview Regional Hospital
  • Arizona
    • Scottsdate, Arizona, United States, 85251
      • Arizona Heart Hospital
  • California
    • Ventura, California, United States, 93003
      • Community Memorial Hospital
    • Watsonville, California, United States, 95076
      • Watsonville Community Hospital
  • Florida
    • Inverness, Florida, United States, 34452
      • Citrus Memorial Hospital
    • Kissimmee, Florida, United States, 34741
      • Osceola Regional Medical Center
    • Miami, Florida, United States, 33136
      • University of Miami
    • Orlando, Florida, United States, 32806
      • Orlando Regional Hospital
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Memorial Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Medical Center
    • Atlanta, Georgia, United States, 30345
      • Veteran's Administration Medical Center
    • Marietta, Georgia, United States, 30060
      • Wellstar Kennestone Hospital
  • Illinois
    • Rock Island, Illinois, United States, 61201
      • Trinity Medical Center
    • Springfield,, Illinois, United States, 62769
      • St. John's Hospital
  • Indiana
    • Hobart, Indiana, United States, 46342
      • St. Mary's Medical
    • Munster, Indiana, United States, 46321
      • Community Hospital, Munster
    • Munster, Indiana, United States, 46321
      • St. Margaret Mercy
  • Louisiana
    • Monroe, Louisiana, United States, 71201
      • P and S Surgical Hospital
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University Hospital
    • Salisbury, Maryland, United States, 21804
      • Penninsula Regional Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
    • Lansing, Michigan, United States, 48910
      • Sparrow Hospital
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital
  • Mississippi
    • Biloxi, Mississippi, United States, 39532
      • Gulfport Memorial Hospital
    • Biloxi, Mississippi, United States, 39534
      • Keesler Air Force Base Hospital
    • Hattiesburg, Mississippi, United States, 39401
      • Southern Heart Center
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • Alegent Health
  • New Jersey
    • Englewood, New Jersey, United States, 07631
      • Englewood Hospital and Medical Center
    • Hamilton, New Jersey, United States, 08690
      • St. Francis Hospital
    • Newark, New Jersey, United States, 07112
      • Newark Beth Israel Hospital
    • Ridgewood, New Jersey, United States, 07450
      • Valley Hospital
    • Sewell, New Jersey, United States, 08080
      • Our Lady of Lourdes Hospital
  • New York
    • New York, New York, United States, 10025
      • St. Luke's - Roosevelt Hospital
  • North Carolina
    • Hickory, North Carolina, United States, 28601
      • Frye Regional Medical Center
  • Ohio
    • Youngstown, Ohio, United States, 44510
      • Catholic Health Partners
  • Pennsylvania
    • Doylestown, Pennsylvania, United States, 18901
      • Doylestown Hospital
    • Harrisburg, Pennsylvania, United States, 17110
      • Pinnacle Health Harrisburg Hospital
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • York, Pennsylvania, United States, 17403
      • York Hospital
  • Rhode Island
    • Woonsocket, Rhode Island, United States, 02895
      • Landmark Medical Center
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Stern Cardiovascular Foundation
    • Knoxville, Tennessee, United States, 37920
      • University of Tenn. Medical Center - Knoxville
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Heart Institute - St. Luke's Episcopal Hospital
    • San Antonio, Texas, United States, 78258
      • NE Methodist
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who have undergone CIED replacement with an ICD or CRT, with or without (CRT retrospective group only) an TYRX Anti-bacterial Envelope, at US medical centers.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
CIED replacement with CRT and TYRX; (Prospective Arm) Patients who have undergone CIED replacement with a CRT and the TYRX Anti-bacterial envelope, with or without lead revision.
CIED replacement with ICD and TYRX; (Prospective Arm) Patients who have undergone CIED replacement with an ICD and the TYRX Anti-bacterial envelope, with or without lead revision.
CIED replacement with ICD or CRT and TYRX; (Prospective Arm) Patients who have undergone CIED replacement with an ICD or CRT and the TYRX Anti-bacterial envelope, with or without lead revision.
CIED replacement w/ CRT & no TYRX; (Retrospective Case-Control Arm) Patients who have undergone CIED replacement with a CRT and no TYRX Anti-bacterial envelope, with or without lead revision/addition.
CIED replacement w/ CRT & TYRX vs. Case Match Arm; Patients who have undergone CIED replacement with a CRT and TYRX Anti-bacterial envelope, with or without lead revision/addition. Cohort is TYRX Case, Matched to Retrospective Case-Control Arm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major CIED Infection	CIED Major Infections	12 months
CIED Mechanical Complication	All mechanical Complications related to CIED Implant	12 months

Collaborators and Investigators

• Sponsor: TYRX, Inc.

Publications and helpful links

General Publications

• Sohail MR, Henrikson CA, Braid-Forbes MJ, Forbes KF, Lerner DJ. Comparison of mortality in women versus men with infections involving cardiovascular implantable electronic device. Am J Cardiol. 2013 Nov 1;112(9):1403-9. doi: 10.1016/j.amjcard.2013.06.031. Epub 2013 Aug 22.
• Ballo P, Chiodi L, Zuppiroli A. Cardiac implantable electronic devices: prevention starts from ethics. Arch Intern Med. 2012 Apr 23;172(8):670-1; author reply 671-2. doi: 10.1001/archinternmed.2012.346. No abstract available.
• Henrikson CA, Sohail MR, Acosta H, Johnson EE, Rosenthal L, Pachulski R, Dan D, Paladino W, Khairallah FS, Gleed K, Hanna I, Cheng A, Lexcen DR, Simons GR. Antibacterial Envelope Is Associated With Low Infection Rates After Implantable Cardioverter-Defibrillator and Cardiac Resynchronization Therapy Device Replacement: Results of the Citadel and Centurion Studies. JACC Clin Electrophysiol. 2017 Oct;3(10):1158-1167. doi: 10.1016/j.jacep.2017.02.016. Epub 2017 May 31.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: January 5, 2010
• First Submitted That Met QC Criteria: January 6, 2010
• First Posted (Estimate): January 7, 2010

Study Record Updates

• Last Update Posted (Estimate): December 24, 2015
• Last Update Submitted That Met QC Criteria: November 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Infection; Pacemaker infection; Defibrillator infection; ICD infection; CRT infection; Cardiovascular implantable electronic device infection; Pacemaker, Artificial; Defibrillators
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: CP-2009-2