Cardiac Implantable Electronic Device Infection
Conditions
Keywords
Pacemaker infection, Defibrillator infection, ICD infection, CRT infection, Cardiovascular implantable electronic device infection, Infection, Pacemaker, Artificial, Defibrillators
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.
Interventions
None listed
Sponsors
TYRX, Inc.
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major CIED Infection | 12 months | CIED Major Infections |
| CIED Mechanical Complication | 12 months | All mechanical Complications related to CIED Implant |
Countries
United States
Participant flow
Recruitment details
First Patient Enrolled = 1 January 2010; Last Patient Enrolled = 7 May 2013
Pre-assignment details
CRT and ICD Implant patients with TYRX Implant; Full analysis cohort = 1,129 patients. 670 patient CRT + TYRX cohort is subset. 459 patient ICD + TYRX is subset. 578 CRT+ TYRX patient cohort is subset matched to 578 patient CRT/no TYRX retrospective patient arm.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 459 |
| CIED Replacement With CRT and 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. | 578 |
| CIED Replacement With CRT and TYRX Vs. Case Match Arm Prospective CRT patients who received a TYRX envelope and had a valid case match retrospective patient. This is a subset of all CRT/TYRX patients | 578 |
| Total | 1,615 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 | 0 |
| Overall Study | Death | 28 | 60 | 26 |
| Overall Study | Lost to Follow-up | 27 | 12 | 0 |
| Overall Study | Multiple Reasons | 4 | 7 | 0 |
| Overall Study | Other | 0 | 19 | 25 |
| Overall Study | Protocol Violation | 2 | 1 | 0 |
| Overall Study | Screen Fail | 21 | 0 | 0 |
| Overall Study | Site Closure | 8 | 0 | 0 |
| Overall Study | Subsequent Procedure | 9 | 24 | 29 |
| Overall Study | Withdrawal by Subject | 8 | 6 | 0 |
Baseline characteristics
| Characteristic | CIED Replacement With ICD and TYRX | CIED Replacement With CRT and no TYRX | CIED Replacement With CRT and TYRX Vs. Case Match Arm | Total |
|---|---|---|---|---|
| Age, Continuous | 70 Years STANDARD_DEVIATION 12.01 | 73 Years STANDARD_DEVIATION 10.94 | 73 Years STANDARD_DEVIATION 10.7 | 72 Years STANDARD_DEVIATION 11.45 |
| Sex: Female, Male Female | 339 Participants | 434 Participants | 444 Participants | 1217 Participants |
| Sex: Female, Male Male | 120 Participants | 144 Participants | 134 Participants | 398 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 96 / 578 | 46 / 459 |
Outcome results
Primary
CIED Mechanical Complication
All mechanical Complications related to CIED Implant
Time frame: 12 months
Population: TYRX implants vs. published comparator are prospective arm patients. Non-TYRX CIED retrospective arm vs. TYRX CIED replacements are nested, case-control cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CIED Replacement With CRT and TYRX | CIED Mechanical Complication | 3.1 percentage of Participants |
| CIED Replacement With CRT and no TYRX | CIED Mechanical Complication | 5.5 percentage of Participants |
| CIED Replacement With CRT and TYRX vs. Case Match Arm | CIED Mechanical Complication | 5.4 percentage of Participants |
p-value: 0.000595% CI: [3.3, 5.8]1-sided Chi-square
p-value: 0.044495% CI: [1.7, 5.1]1-sided Chi-square test
Comparison: All types of mechanical complications combined.p-value: 0.000695% CI: [3.8, 5.4]1-sided Chi-squared test
Comparison: All mechanical complications, retrospective, non-TYRX cohortp-value: 0.074595% CI: [3.7, 7.5]Chi-squared
Primary
Major CIED Infection
CIED Major Infections
Time frame: 12 months
Population: Evaluable patients that have valid entry criteria
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CIED Replacement With CRT and TYRX | Major CIED Infection | 0.6 percentage of Participants |
| CIED Replacement With CRT and no TYRX | Major CIED Infection | 1.0 percentage of Participants |
| CIED Replacement With CRT and TYRX vs. Case Match Arm | Major CIED Infection | 0.7 percentage of Participants |
p-value: 0.0023Fisher Exact
p-value: 0.0052Fisher Exact
p-value: 0.0176Fisher Exact
p-value: 0.3764Fisher Exact