Clinical trial NCT01043705: TYRX™ Envelope for Prevention of Infection Following Replacement With a CRT or ICD
Official title: Centurion and Citadel Studies of TYRX™ Anti-Bacterial Envelope and Custom Mesh for Prevention of Infection Following CIED Replacement With a CRT or ICD
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiac Implantable Electronic Device Infection
Keywords: Pacemaker infection
Defibrillator infection
ICD infection
CRT infection
Cardiovascular implantable electronic device infection
Infection
Pacemaker, Artificial
Defibrillators
Lead sponsor: TYRX, Inc.
Sponsor class: INDUSTRY
First posted: 2010-01-07
Enrollment: 1262
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Major CIED Infection
timeFrame: 12 months
measure: CIED Mechanical Complication
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Princeton Medical Center
state: Alabama
city: Decatur
country: United States
facility: Decatur General Hospital
state: Alabama
city: Florence
country: United States
facility: Eliza Coffee Memorial Hospital
state: Alabama
city: Gadsden
country: United States
facility: Riverview Regional Hospital
state: Alabama
city: Scottsdate
country: United States
facility: Arizona Heart Hospital
state: Arizona
city: Ventura
country: United States
facility: Community Memorial Hospital
state: California
city: Watsonville
country: United States
facility: Watsonville Community Hospital
state: California
city: Inverness
country: United States
facility: Citrus Memorial Hospital
state: Florida
city: Kissimmee
country: United States
facility: Osceola Regional Medical Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Regional Hospital
state: Florida
city: Tallahassee
country: United States
facility: Tallahassee Memorial Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Medical Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Veteran's Administration Medical Center
state: Georgia
city: Marietta
country: United States
facility: Wellstar Kennestone Hospital
state: Georgia
city: Rock Island
country: United States
facility: Trinity Medical Center
state: Illinois
city: Springfield,
country: United States
facility: St. John's Hospital
state: Illinois
city: Hobart
country: United States
facility: St. Mary's Medical
state: Indiana
city: Munster
country: United States
facility: Community Hospital, Munster
state: Indiana
city: Munster
country: United States
facility: St. Margaret Mercy
state: Indiana
city: Monroe
country: United States
facility: P and S Surgical Hospital
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins University Hospital
state: Maryland
city: Salisbury
country: United States
facility: Penninsula Regional Medical Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Biloxi
country: United States
facility: Gulfport Memorial Hospital
state: Mississippi
city: Biloxi
country: United States
facility: Keesler Air Force Base Hospital
state: Mississippi
city: Hattiesburg
country: United States
facility: Southern Heart Center
state: Mississippi
city: Omaha
country: United States
facility: Alegent Health
state: Nebraska
city: Englewood
country: United States
facility: Englewood Hospital and Medical Center
state: New Jersey
city: Hamilton
country: United States
facility: St. Francis Hospital
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Hospital
state: New Jersey
city: Ridgewood
country: United States
facility: Valley Hospital
state: New Jersey
city: Sewell
country: United States
facility: Our Lady of Lourdes Hospital
state: New Jersey
city: New York
country: United States
facility: St. Luke's - Roosevelt Hospital
state: New York
city: Hickory
country: United States
facility: Frye Regional Medical Center
state: North Carolina
city: Youngstown
country: United States
facility: Catholic Health Partners
state: Ohio
city: Doylestown
country: United States
facility: Doylestown Hospital
state: Pennsylvania
city: Harrisburg
country: United States
facility: Pinnacle Health Harrisburg Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: York
country: United States
facility: York Hospital
state: Pennsylvania
city: Woonsocket
country: United States
facility: Landmark Medical Center
state: Rhode Island
city: Germantown
country: United States
facility: Stern Cardiovascular Foundation
state: Tennessee
city: Knoxville
country: United States
facility: University of Tenn. Medical Center - Knoxville
state: Tennessee
city: Houston
country: United States
facility: Texas Heart Institute - St. Luke's Episcopal Hospital
state: Texas
city: San Antonio
country: United States
facility: NE Methodist
state: Texas
city: Milwaukee
country: United States
facility: Aurora Health Care
state: Wisconsin
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.